US20040062804A1 - Modified release dosage forms - Google Patents

Modified release dosage forms Download PDF

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Publication number
US20040062804A1
US20040062804A1 US10/432,488 US43248803A US2004062804A1 US 20040062804 A1 US20040062804 A1 US 20040062804A1 US 43248803 A US43248803 A US 43248803A US 2004062804 A1 US2004062804 A1 US 2004062804A1
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US
United States
Prior art keywords
dosage form
core
active ingredient
shell
release
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/432,488
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English (en)
Inventor
Der-Yang Lee
Shun-Por Li
Daniel McTeigue
Narendra Parikh
Harry Sowden
Martin Thomas
David Wynn
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Johnson and Johnson Consumer Inc
Original Assignee
McNeil PPC Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/966,450 external-priority patent/US6982094B2/en
Priority claimed from US09/967,414 external-priority patent/US6742646B2/en
Priority claimed from US09/966,939 external-priority patent/US6837696B2/en
Priority claimed from US09/966,509 external-priority patent/US6767200B2/en
Priority claimed from US09/966,497 external-priority patent/US7122143B2/en
Application filed by McNeil PPC Inc filed Critical McNeil PPC Inc
Priority to US10/432,488 priority Critical patent/US20040062804A1/en
Assigned to MCNEIL-PPC, INC. reassignment MCNEIL-PPC, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PARIKH, NARENDRA, WYNN, DAVID, LEE, DER-YANG, LI, SHUN-POR, MCTEIGUE, DANIEL, SOWDEN, HARRY S., THOMAS, MARTIN
Publication of US20040062804A1 publication Critical patent/US20040062804A1/en
Abandoned legal-status Critical Current

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Definitions

  • This invention relates to modified release dosage forms such as modified release pharmaceutical compositions. More particularly, this invention relates to modified release dosage forms having a two-portion shell for delivering one or more active ingredients in a controlled or delayed manner upon contacting of the dosage form with a liquid medium.
  • Modified release pharmaceutical dosage forms have long been used to optimize drug delivery and enhance patient compliance, especially by reducing the number of doses of medicine the patient must take in a day.
  • a drug one particularly preferred type of active ingredient
  • the rate at which an orally delivered pharmaceutical active ingredient reaches its site of action in the body depends on a number of factors, including the rate and extent of drug absorption through the g.i. mucosa.
  • the drug To be absorbed into the circulatory system (blood), the drug must first be dissolved in the g.i. fluids.
  • diffusion across the g.i. membranes is relatively rapid compared to dissolution.
  • the dissolution of the active ingredient is the rate limiting step in drug absorption, and controlling the rate of dissolution allows the formulator to control the rate of drug absorption into the circulatory system of a patient.
  • modified release dosage forms provide a desired blood concentration versus time (pharmacokinetic, or PK) profile for the drug.
  • PK profile for a drug is governed by the rate of absorption of the drug into the blood, and the rate of elimination of the drug from the blood.
  • the type of PK profile desired depends, among other factors, on the particular active ingredient, and physiological condition being treated.
  • a particularly desirable PK profile for a number of drugs and conditions is one in which the level of drug in the blood is maintained essentially constant (i.e. the rate of drug absorption is approximately equal to the rate of drug elimination) over a relatively long period of time.
  • Such systems have the benefit of reducing the frequency of dosing, improving patient compliance, as well as minimizing side effects while maintaining full therapeutic efficacy.
  • a dosage form which provides a “zero-order,” or constant release rate of the drug is useful for this purpose. Since zero-order release systems are difficult to achieve, systems which approximate a constant release rate, such as for example first-order and square root of time profiles are often used to provide sustained (e.g. prolonged, extended, or retarded) release of a drug.
  • Another particularly desirable PK profile is achieved by a dosage form that delivers a delayed release dissolution profile, in which the release of drug from the dosage form is delayed for a pre-determined time after ingestion by the patient.
  • the delay period (“lag time”) can be followed either by prompt release of the active ingredient (“delayed burst”), or by sustained (prolonged, extended, or retarded) release of the active ingredient (“delayed then sustained”).
  • Another particularly desirable PK profile is a “pulsatile” profile, in which for example, a first dose is delivered immediately, followed by a delay corresponding approximately to the time during which a therapeutic concentration of the first dose is maintained in the blood, followed by either prompt or sustained release of a subsequent dose of the same drug.
  • a pharmaceutical dosage form it is also particularly desirable for a pharmaceutical dosage form to deliver more than one drug at a modified rate. Because the onset and duration of the therapeutic efficacy of drugs vary widely, as do their absorption, distribution, metabolism, and elimination, it is often desirable to modify the release of different drugs in different ways, or to have a first active ingredient immediately released from the dosage form, while a second drug is released in a delayed, controlled, sustained, prolonged, extended, or retarded manner.
  • Well known mechanisms by which a dosage form (or drug delivery system) can deliver drug at a controlled rate include diffusion, erosion, and osmosis.
  • One classic diffusion-controlled release system comprises a “reservoir” containing the active ingredient, surrounded by a “membrane” through which the active ingredient must diffuse to be absorbed into the bloodstream of the patient.
  • the rate of drug release, dM/dt depends on the area (A) of the membrane, the diffusional pathlength (1), the concentration gradient ( ⁇ C) of the drug across the membrane, the partition coefficient (K) of the drug into the membrane, and the diffusion coefficient (D):
  • diffusion-controlled systems generally deliver a non-constant release rate.
  • rate of drug release from diffusion-controlled release systems typically follows first order kinetics.
  • Another common type of diffusion-controlled release system comprises active ingredient, distributed throughout an insoluble porous matrix through which the active ingredient must diffuse in order to be absorbed into the bloodstream of the patient.
  • the amount of drug release (M) at a given time at sink conditions i.e. drug concentration at the matrix surface is much greater than drug concentration in the bulk solution
  • the amount of drug release (M) at a given time at sink conditions depends on the area (A) of the matrix, the diffusion coefficient (D), the porosity (E) and tortuosity (T) of the matrix, the drug solubility (Cs) in the dissolution medium, time (t) and the drug concentration (Cp) in the dosage form:
  • the amount of drug released is generally proportional to the square root of time. Assuming factors such as matrix porosity and tortuosity are constant within the dosage form, a plot of amount of drug released versus the square root of time should be linear.
  • a commonly used erosion-controlled release system comprises a “matrix” throughout which the drug is distributed.
  • the matrix typically comprises a material which swells at the surface, and slowly dissolves away layer by layer, liberating drug as it dissolves.
  • the rate of drug release (dM/dt) in these systems depends on the rate of erosion (dx/dt) of the matrix, the concentration profile in the matrix, and the surface area (A) of the system:
  • Another type of erosion controlled delivery system employs materials which swell and dissolve slowly by surface erosion to provide a delayed release of pharmaceutical active ingredient. Delayed release is useful, for example in pulsatile or repeat action delivery systems, in which an immediate release dose is delivered, followed by a pre-determined lag time before a subsequent dose is delivered from the system.
  • the lag time (T 1 ) depends on the thickness (h) of the erodible layer, and the rate of erosion (dx/dt) of the matrix, which in turn depends on the swelling rate and solubility of the matrix components:
  • dM/dt is generally described by either the diffusion-controlled or erosion-controlled equations above, and T 1 is the lag time.
  • a shell, or coating, which confers modified release properties is typically applied via conventional methods, such as for example, spray-coating in a coating pan.
  • Pan-coating produces a single shell which essentially surrounds the core.
  • the single shell is inherently limited in its functionality. It is possible via pan-coating to apply multiple concentric shells, each with a different functionality, however such systems are limited in that the outer shell must first dissolve before the functionality conferred by each successive layer can be realized. It is also known, via pan coating, to deliver a first dose of active ingredient from a coating, and a second dose of active ingredient from a core.
  • Dosage forms having sprayed coatings which provide delayed release are described, for example, in G. Maffione et al., “High-Viscosity HPMC as a Film-Coating Agent,” Drug Development and Industrial Pharmacy (1993) 19(16), pp. 2043-2053.
  • U.S. Pat. No. 4,576,604 discloses an osmotic device (dosage form) comprising a drug compartment surrounded by a wall (coating) in which the coating may comprise an immediate release dose of drug, and the inner drug compartment may comprise a sustained release dose of drug.
  • the coating compositions that can be applied via spraying are limited by their viscosity.
  • Spray coating methods suffer the further limitations of being time-intensive and costly. Several hours of spraying may be required to spray an effective amount of coating to control the release of an active ingredient. Coating times of 8 to 24 hours are not uncommon.
  • conventional modifed release systems may be prepared by compression, to produce either multiple stacked layers, or core and shell configurations.
  • Modified release dosage forms prepared via compression are exemplified in U.S. Pat. Nos. 5,738,874 and 6,294,200, and WO 99/51209. It is possible, via compression-coating, to produce a 2-portion shell, which may function as a barrier, or release delaying coating, however compression-coated systems are limited by the shell thickness and shell composition.
  • Gunsel et al. “Compression-coated and layer tablets” in Pharmaceutical Dosage Forms—Tablets , edited by H. A. Lieberman, L. Lachman, J. B. Schwartz (2nd ed., rev. and expanded.
  • compression-coated dosage forms are not optimal for providing certain types of modified release, such as for example diffusion-controlled release which is not preceded by a lag-time.
  • U.S. Pat. No. 5,738,874 discloses a 3-layer pharmaceutical compressed tablet capable of liberating one or more drugs at different release rates, in which an immediate release dose of active may be contained in a compressed coating layer, and the compressed coating layer has a weight which is 230% to 250% of the weight of the core, and a sustained release dose of active ingredient is contained in the core.
  • the outer compressed coating layer may function via an erosion mechanism to delay release of an active ingredient contained in the core.
  • U.S. Pat. No. 5,464,633 discloses delayed-release dosage forms in which an extermal coating layer was applied by a compression coating process. The coating level ranged from 105 percent to 140 percent of the weight of the core in order to yield product with the desired time delayed profile.
  • the dosage form of this invention comprises: (a) at least one active ingredient; (b) a core; and (c) a shell which resides upon at least a portion of the core, wherein the shell is substantially free of pores having a diameter of 0.5 to 5.0 microns, the shell comprises a first shell portion and a second shell portion which are compositionally different and the dosage form provides a modified release profile of the active ingredient upon contacting of the dosage form with a liquid medium.
  • the dosage form of this invention comprises: (a) at least one active ingredient; (b) a core comprising first and second core portions; and (c) a shell portion which surrounds at least one of the first or second core portions.
  • the dosage form of this invention comprises: (a) at least one active ingredient; (b) a core comprising first and second core portions; and (c) a shell portion which surrounds only the first core portion, wherein the second core portion is not enclosed by a shell portion, and is exposed immediately to the liquid medium upon contact of the dosage form with a liquid medium.
  • the dosage form of this invention comprises: (a) at least one active ingredient; (b) a core comprising first and second core portions; and (c) a shell which resides upon at least a portion of the core, wherein the shell comprises first and second shell portions such that the first shell portion resides upon at least a portion of the first core portion and the second shell portion resides upon at least a portion of the second core portion, and at least one of the first or second core portions or first or second shell portions provides a modified release profile of an active ingredient upon contacting of the dosage form with a liquid medium.
  • At least one of the first or second shell portions comprises an active ingredient.
  • first and second shell portions each comprise an active ingredient.
  • At least one of the first or second shell portions comprises an active ingredient which is immediately released therefrom upon contacting of the dosage form with a liquid medium.
  • At least one of the first or second shell portions provides modified release of at least one active ingredient contained therein.
  • At least one of the first or second shell portions comprises at least one active ingredient, and the release of the active ingredient contained in the shell portion is sustained, prolonged, extended, or retarded upon contacting of the dosage form with a liquid medium.
  • first and second shell portions each provide different release profiles for the active ingredients contained therein upon contacting of the dosage form with a liquid medium.
  • At least one of the first or second shell portions provides modified release of at least one active ingredient contained in the underlying core or portion thereof.
  • the core comprises particles comprising at least one active ingredient.
  • the particles comprise a coating capable of providing a modified release profile of the active ingredient in the particles upon contacting of the core with a liquid medium.
  • the core comprises a first core portion and a second core portion, at least one core portion comprises at least one active ingredient, and at least one active ingredient contained in the first or second core portion exhibits a modified release profile upon contacting of the dosage form with a liquid medium.
  • the core comprises a first core portion and a second core portion, at least one core portion comprises at least one active ingredient, and the materials comprising the first or second core portion provide a modification to the release of an active ingredient contained therein upon contacting of the dosage form with a liquid medium.
  • the core comprises a first core portion and a second core portion, at least one core portion comprises at least one active ingredient, and the materials comprising the first or second shell portion provide a modification to the release of an active ingredient contained in the underlying core portion upon contacting of the dosage form with a liquid medium.
  • the core comprises a first core portion and a second core portion, at least one core portion comprises at least one active ingredient, and the release of the active ingredient contained in the core portion is delayed upon contacting of the dosage form with a liquid medium.
  • the core comprises a first core portion and a second core portion, at least one core portion comprises at least one active ingredient, and the release of the active ingredient contained in the core portion is sustained, prolonged, extened, or retarded upon contacting of the dosage form with a liquid medium.
  • At least one of the first or second core portions comprises an active ingredient which is immediately released therefrom upon breach of the surrounding shell portion and contacting of the core portion with a liquid medium.
  • the core comprises a first core portion and a second core portion, each core portion comprises an active ingredient, and each of the active ingredients exhibits a modified release profile upon contacting of the dosage form with a liquid medium.
  • the release profiles of the active ingredients in the first and second core portions are substantially similar.
  • the release profiles of the first and second core portions are substantially different.
  • the core comprises a first core portion and a second core portion, only one of the first or second core portions comprises one or more active ingredients, and at least one active ingredient exhibits a modified release profile upon contacting of the dosage form with a liquid medium.
  • the core is a bi-layer tablet.
  • At least one of the first or second core portions comprises particles comprising at least one active ingredient.
  • the particles comprise a coating capable of providing a modifed release profile of the active ingredient in the particles upon contacting of the core with a liquid medium.
  • the core is substantially free of pores having a diameter of 0.5-5.0 microns.
  • the first core portion comprises a first active ingredient
  • the second core portion does not comprise an active ingredient
  • the first core portion comprises a first active ingredient
  • the second core portion comprises a second active ingredient
  • the first shell portion provides for modified release of the first active ingredient
  • the second shell portion provides for modified release of the second active ingredient
  • the first shell portion provides for immediate release of the first active ingredient
  • the second shell portion provides for modified release of the second active ingredient
  • the first core portion comprises a first active ingredient
  • the second core portion comprises a second active ingredient
  • the first shell portion comprises a third active ingredient
  • the second shell portion comprises a fourth active ingredient
  • At least one of the first or second core portions is substantially free of pores having a diameter of 0.5-5.0 microns.
  • At least one of the first or second shell portions is substantially free of pores having a diameter of 0.5-5.0 microns.
  • one or more shell portions functions as a barrier to prevent release therethrough of an active ingredient contained in the underlying core or core portion.
  • At least one of the first or second shell portions comprises a thermal-reversible carrier selected from the group consisting of polyethylene glycol, polyethylene oxide and combinations thereof.
  • At least one of the first or second shell portions comprises a release modifying excipent selected from the group consisting of shellac, hydroxypropylmethylcellulose, polyethylene oxide, ammonio methacrylate copolymer type B, and combinations thereof.
  • At least one of the first or second shell portions comprises a film-former selected from the group consisting of cellulose acetate, ammonio methacrylate copolymer type B, shellac, hydroxypropylmethylcellulose, and combinations thereof.
  • At least one of the first or second shell portions comprises a swellable erodible hydrophilic material selected from the group consisting of selected from cross-linked polyvinyl pyrrolidone, cross-linked agar, cross-linked carboxymethylcellose sodium, and combinations thereof.
  • At least one of the first or second shell portions further comprises a plasticizer.
  • At least one of the first or second shell portions comprises a pore former.
  • an outer coating covers at least a portion of the shell.
  • the shell is prepared using a solvent-free molding process.
  • the shell comprises at least 30% by weight of a thermal-reversible carrier.
  • the shell comprises up to 55% by weight of a swellable, erodible hydrophilic material.
  • the shell is prepared using a solvent-based molding process.
  • the shell comprises at least 15% by weight of a film-former.
  • the shell comprises at least 55% by weight of a release-modifying agent.
  • FIG. 1 depicts a cross-sectional side view of one embodiment of the dosage form of this invention.
  • FIG. 2 depicts a cross-sectional side view of another embodiment of the dosage form of this invention.
  • FIG. 3 depicts the % release of active ingredient vs. time measured for the dosage form of Example 1.
  • FIG. 4 depicts the % release of active ingredient vs. time measured for the dosage form of Example 2.
  • the term “dosage form” applies to any solid object, semi-solid, or liquid composition designed to contain a specific pre-determined amount (dose) of a certain ingredient, for example an active ingredient as defined below.
  • Suitable dosage forms may be pharmaceutical drug delivery systems, including those for oral administration, buccal administration, rectal administration, topical or mucosal delivery, or subcutaneous implants, or other implanted drug delivery systems; or compositions for delivering minerals, vitamins and other nutraceuticals, oral care agents, flavorants, and the like.
  • the dosage forms of the present invention are considered to be solid, however they may contain liquid or semi-solid components.
  • the dosage form is an orally administered system for delivering a pharmaceutical active ingredient to the gastro-intestinal tract of a human.
  • the dosage forms of the invention exhibit modified release of one or more active ingredients contained therein.
  • the active ingredient or ingredients may be found within the core, the shell, or a portion or combination thereof.
  • the term “modified release” shall apply to dosage forms, coatings, shells, cores, portions thereof, or compositions that alter the release of an active ingredient in any manner.
  • the active ingredient or ingredients that are released in a modified manner may be contained within the coating, shell, core, composition, or portion thereof providing the modification.
  • the modified release active ingredient may be contained in a different portion of the dosage form from the coating, shell, core, composition, or portion thereof providing the modification; for example the modified release active ingredient may be contained in a core portion, and the modification may be provided by the overlaying shell portion.
  • Types of modified release include controlled, prolonged, sustained, extended, delayed, pulsatile, repeat action, and the like. Suitable mechanisms for achieving these types of modified release include diffusion, erosion, surface area control via geometry and/or impermeable barriers, or other mechanisms known in the art. Moreover, the modified release properties of the dosage form may be achieved through design of the core or a portion thereof, or the first shell portion, or the second shell portion, or a combination of two or more of these parts of the dosage form.
  • the dissolution profile of each active ingredient from the dosage form may be governed by a sum of contributions from the properties of the various portions. Additionally, a single portion, for example a core portion, may possess a combination of erosional and diffusional properties. In any case, the dissolution rate of a particular active ingredient from the dosage form will be the sum of the contributions from all the various mechanisms contributed by the various portions of the dosage form which effect the release of that particular active ingredient, as depicted by the following equation:
  • Rate total . . . . . . X 1 Rate 1 . . . +X 2 Rate 2 . . . +X 3 Rate 3 . . . +X n Rate n
  • X 1 , X 2 , X 3 , . . . X n are the relative contribution fractions of to the total release rate
  • Rate 1 , Rate 2 , Rate 3 , . . . Rate n are the various release rates contributed by effects of the various portions of the dosage form on a particular active ingredient.
  • Suitable active ingredients for use in this invention include for example pharmaceuticals, minerals, vitamins and other nutraceuticals, oral care agents, flavorants and mixtures thereof.
  • suitable pharmaceuticals include analgesics, anti-inflammatory agents, antiarthritics, anesthetics, antihistamines, antitussives, antibiotics, anti-infective agents, antivirals, anticoagulants, antidepressants, antidiabetic agents, antiemetics, antiflatulents, antifungals, antispasmodics, appetite suppressants, bronchodilators, cardiovascular agents, central nervous system agents, central nervous system stimulants, decongestants, oral contraceptives, diuretics, expectorants, gastrointestinal agents, migraine preparations, motion sickness products, mucolytics, muscle relaxants, osteoporosis preparations, polydimethylsiloxanes, respiratory agents, sleep-aids, urinary tract agents and mixtures thereof.
  • Suitable oral care agents include breath fresheners, tooth whiteners, antimicrobial agents, tooth mineralizers, tooth decay inhibitors, topical anesthetics, mucoprotectants, and the like.
  • Suitable flavorants include menthol, peppermint, mint flavors, fruit flavors, chocolate, vanilla, bubblegum flavors, coffee flavors, liqueur flavors and combinations and the like.
  • Suitable gastrointestinal agents include antacids such as calcium carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate, aluminum hydroxide, sodium bicarbonate, dihydroxyaluminum sodium carbonate; stimulant laxatives, such as bisacodyl, cascara sagrada, danthron, senna, phenolphthalein, aloe, castor oil, ricinoleic acid, and dehydrocholic acid, and mixtures thereof; H2 receptor antagonists, such as famotadine, ranitidine, cimetadine, nizatidine; proton pump inhibitors such as omeprazole or lansoprazole; gastrointestinal cytoprotectives, such as sucraflate and misoprostol; gastrointestinal prokinetics, such as prucalopride, antibiotics for H.
  • antacids such as calcium carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate, aluminum hydroxide, sodium bicarbonate, dihydroxyaluminum
  • pylori such as clarithromycin, amoxicillin, tetracycline, and metronidazole
  • antidiarrheals such as diphenoxylate and loperamide
  • glycopyrrolate such as glycopyrrolate
  • antiemetics such as ondansetron
  • analgesics such as mesalamine.
  • the active ingredient may be selected from bisacodyl, famotadine, ranitidine, cimetidine, prucalopride, diphenoxylate, loperamide, lactase, mesalamine, bismuth, antacids, and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof.
  • the active ingredient is selected from analgesics, anti-inflammatories, and antipyretics, e.g. non-steroidal anti-inflammatory drugs (NSAIDs), including propionic acid derivatives, e.g. ibuprofen, naproxen, ketoprofen and the like; acetic acid derivatives, e.g. indomethacin, diclofenac, sulindac, tolmetin, and the like; fenamic acid derivatives, e.g. mefanamic acid, meclofenamic acid, flufenamic acid, and the like; biphenylcarbodylic acid derivatives, e.g.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • the active ingredient is selected from propionic acid derivative NSAID, e.g. ibuprofen, naproxen, flurbiprofen, fenbufen, fenoprofen, indoprofen, ketoprofen, fluprofen, pirprofen, carprofen, oxaprozin, pranoprofen, suprofen, and pharmaceutically acceptable salts, derivatives, and combinations thereof.
  • NSAID e.g. ibuprofen, naproxen, flurbiprofen, fenbufen, fenoprofen, indoprofen, ketoprofen, fluprofen, pirprofen, carprofen, oxaprozin, pranoprofen, suprofen, and pharmaceutically acceptable salts, derivatives, and combinations thereof.
  • the active ingredient may be selected from acetaminophen, acetyl salicylic acid, ibuprofen, naproxen, ketoprofen, flurbiprofen, diclofenac, cyclobenzaprine, meloxicam, rofecoxib, celecoxib, and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof.
  • the active ingredient may be selected from pseudoephedrine, phenylpropanolamine, chlorpheniramine, dextromethorphan, diphenhydramine, astemizole, terfenadine, fexofenadine, loratadine, desloratadine, cetirizine, mixtures thereof and pharmaceutically acceptable salts, esters, isomers, and mixtures thereof.
  • Suitable polydimethylsiloxanes which include, but are not limited to dimethicone and simethicone, are those disclosed in U.S. Pat. Nos. 4,906,478, 5,275,822, and 6,103,260, the contents of each is expressly incorporated herein by reference.
  • simethicone refers to the broader class of polydimethylsiloxanes, including but not limited to simethicone and dimethicone.
  • the active ingredient or ingredients are present in the dosage form in a therapeutically effective amount, which is an amount that produces the desired therapeutic response upon oral administration and can be readily determined by one skilled in the art. In determining such amounts, the particular active ingredient being administered, the bioavailability characteristics of the active ingredient, the dosing regimen, the age and weight of the patient, and other factors must be considered, as known in the art.
  • the dosage form comprises at least about 1 weight percent, preferably, the dosage form comprises at least about 5 weight percent, e.g. about 20 weight percent of a combination of one or more active ingredients.
  • the core comprises a total of at least about 25 weight percent (based on the weight of the core) of one or more active ingredients.
  • the active ingredient or ingredients may be present in the dosage form in any form.
  • the active ingredient may be dispersed at the molecular level, e.g. melted or dissolved, within the dosage form, or may be in the form of particles, which in turn may be coated or uncoated.
  • the particles typically have an average particle size of about 1-2000 microns. In one preferred embodiment, such particles are crystals having an average particle size of about 1-300 microns. In another preferred embodiment, the particles are granules or pellets having an average particle size of about 50-2000 microns, preferably about 50-1000 microns, most preferably about 100-800 microns.
  • the core may contain coated particles of one or more active ingredients, in which the particle coating confers a release modifying function, as is well known in the art.
  • suitable release modifying coatings for particles are described in U.S. Pat. Nos. 4,173,626; 4,863,742; 4,980,170; 4,984,240; 5,286,497; 5,912,013; 6,270,805; and 6,322,819.
  • Commercially available modified release coated active particles may also be employed. Accordingly, all or a portion of one or more active ingredients in the core may be coated with a release-modifying material.
  • the active ingredient or ingredients are preferably capable of dissolution upon contact with a fluid such as water, gastric fluid, intestinal fluid or the like.
  • a fluid such as water, gastric fluid, intestinal fluid or the like.
  • the dissolution characteristics of at least one active ingredient meets USP specifications for immediate release tablets containing the active ingredient.
  • USP 24 specifies that in pH 5.8 phosphate buffer, using USP apparatus 2 (paddles) at 50 rpm, at least 80% of the acetaminophen contained in the dosage form is released therefrom within 30 minutes after dosing, and for ibuprofen tablets, USP 24 specifies that in pH 7.2 phosphate buffer, using USP apparatus 2 (paddles) at 50 rpm, at least 80% of the ibuprofen contained in the dosage form is released therefrom within 60 minutes after dosing. See USP 24, 2000 Version, 19-20 and 856 (1999).
  • the immediately released active ingredient is preferably contained in the shell or on the surface of the shell, e.g. in a further coating surrounding at least a portion of the shell.
  • the dissolution characteristics of one or more active ingredients are modified: e.g. controlled, sustained, extended, retarded, prolonged, delayed and the like.
  • the modified release active or actives are preferably contained in the core.
  • FIG. 1 is a cross-sectional side view of a dosage form 2 which comprises a core 4 and first and second shell portions 6 and 8 , respectively, which in this embodiment surround the core.
  • the first and second shell portions 6 and 8 may reside upon a portion of the core 4 without surrounding the core 4 .
  • FIG. 2 is a cross-sectional side view of a dosage form 202 which comprises a core 204 having first and second portions 203 and 205 , respectively, and first and second shell portions 206 and 208 , respectively, which in this embodiment surround the core.
  • the first and second shell portions 206 and 208 may reside upon first and second core portions 203 and 205 , respectively, without surrounding the core 204 .
  • one or more shell portions contain active ingredient which is released essentially immediately upon ingestion of the dosage form.
  • the shell portion preferably comprises materials which exhibit rapid dissolution in gastro-intestinal fluids.
  • one or more shell portions function as a diffusional membrane which contains pores through which fluids can enter the dosage form, and dissolved active ingredient can be released in a sustained, extended, prolonged or retarded manner.
  • the rate of release of active ingredient from an underlying core portion will depend upon the total pore area in the shell portion, the pathlength of the pores, and the solubility and diffusivity of the active ingredient (in addition to its rate of release from the core portion itself).
  • the release of the active ingredient from the dosage form may be described as controlled, prolonged, sustained or extended.
  • the contribution to active ingredient dissolution from the subject shell portion may follow zero-order, first-order, or square-root of time kinetics.
  • the diffusional membrane shell portion preferrably comprises a release-modifying excipient such as a combination of a pore former and an insoluble edible material such as for example a film forming water insoluble polymer.
  • the thermal-reversible carrier may function by dissolving and forming pores or channels through which the active ingredient may be liberated.
  • one or more shell portions function as an eroding matrix from which active ingredient dispersed in the shell portion is liberated by the dissolution of successive layers of the shell portion surface.
  • the rate of active ingredient release will depend on the dissolution rate of the matrix material in the shell portion.
  • Particularly useful matrix materials for providing surface erosion include those which first absorb liquid, then swell and/or gel prior to dissolving.
  • the eroding matrix shell portion preferably comprises a swellable erodible hydrophilic material.
  • one or more shell portions function as a barrier to prevent release therethrough of an active ingredient contained in the underlying core or core portion.
  • active ingredient is typically released from a portion of the core which is not covered by the barrier shell portion.
  • Such embodiments advantageously allow for control of the surface area for release of the active ingredient.
  • the surface area for release of active ingredient can be maintained substantially constant over time.
  • the release of at least one active ingredient follows substantially zero-order kinetics.
  • the barrier shell portion preferably comprises a water insoluble material such as for example a water insoluble polymer.
  • one or more shell portions function as a delayed release coating to delay release of an active ingredient which is contained in the core or a portion thereof.
  • the lag-time for onset of active ingredient release may be governed by erosion of the coating or diffusion through the coating or a combination thereof.
  • the eroding matrix shell portion preferably comprises a swellable erodible hydrophilic material.
  • the thickness of the shell portion is critical to the release properties of the dosage form.
  • the dosage forms of the invention can be made with precise control over shell thickness.
  • the shell portion or portions are made by the thermal cycle or thermal setting injection molding methods and apparatus described below.
  • one or more core portions function to promptly, e.g. immediately, release one or more active ingredients contained therein upon breach of the surrounding shell portion.
  • the core portion preferably comprises materials which exhibit rapid dissolution in gastro-intestinal fluids, for example the core portion may comprise a disintegrant.
  • one or more core portions function as an eroding matrix from which dispersed active ingredient is liberated by the dissolution of successive layers of the matrix surface.
  • the rate of active ingredient release from the core portion will depend on the dissolution rate of the matrix material.
  • Particularly useful eroding matrix materials for providing surface erosion include those which first absorb liquid, then swell and/or gel prior to dissolving.
  • the eroding matrix core portion preferrably comprises a swellable erodible hydrophilic material.
  • one or more core portions function as a diffusional matrix.
  • the core portion preferably comprises active ingredient, distributed throughout an insoluble porous matrix, which contains pores or channels through which fluids can enter the core portion, and the active ingredient must diffuse to be released from the dosage form.
  • the rate of active ingredient release from the core portion will depend upon the area (A) of the matrix, the diffusion coefficient (D), the porosity (E) and tortuosity (T) of the matrix, the drug solubility (Cs) in the dissolution medium, and the drug concentration (Cp) in the dosage form.
  • a core portion functions as a diffusional matrix
  • the release of the active ingredient from the core portion may be described as controlled, prolonged, sustained, or extended.
  • the contribution to active ingredient dissolution from the subject core portion may follow zero-order, first-order, or preferably square-root of time kinetics.
  • the diffusional matrix core portion preferably comprises a pore former.
  • the release of active ingredient may be further modified by the function of a surrounding shell portion, as described above.
  • the release of the active ingredient from the dosage form will be governed by the sum of all the contributions acting upon it, e.g. from the relevant core and shell portions, and may be described as controlled, prolonged, sustained, extended, delayed, or pulsatile.
  • the dissolution of active ingredient from the dosage form may follow zero-order, first-order, or square-root of time kinetics.
  • the portions may comprise different materials, or be prepared by different methods, or both.
  • a first core portion may be prepared by compression, and a second core portion may be prepared by molding.
  • the core comprises multiple portions, which comprise different active ingredients or have different release-modifying properties, or both; and the shell comprises a corresponding number of multiple portions, which each cover a specific core portion in order to modify or further modify the release of one or more active ingredients contained within the respective core portion.
  • the orientation of the components of the dosage forms of the present invention can be precisely controlled, when manufactured using the thermal cycle and thermal setting apparatus and described below.
  • the dosage form comprises a core comprising a first core portion and a second core portion which are compositionally different, wherein at least one of the first or second core portions comprises an active ingredient; and a shell which surrounds the core and comprises a first shell portion and a second shell portion which are compositionally different, wherein at least one of the first or second shell portions confers a modification to the release of an active ingredient contained in the underlying core portion.
  • the dosage form of the invention comprises at least one active ingredient; a core; a shell which resides upon at least a portion of the core and comprises a first and second shell portion which are compositionally different; and an outer coating which covers at least a portion of the shell.
  • the outer coating may for example cover a portion of the first shell portion, or the second shell portion, or both, or may surround the entire shell.
  • the outer coating comprises an active ingredient, which is released immediately (i.e.
  • the dosage form is a pulsatile drug delivery system, in which one or more shell portions provides for delayed release of a second dose of active ingredient, which is contained in an underlying core portion.
  • the core of the present invention may be prepared by any suitable method, including for example compression and molding, and depending on the method by which it is made, typically comprises active ingredient and a variety of excipients (inactive ingredients which may be useful for conferring desired physical properties to the dosage core).
  • suitable excipients include fillers, binders, disintegrants, lubricants, glidants, and the like, as known in the art.
  • the core preferably further comprises a release-modifying compressible excipient.
  • Suitable fillers for use in making the core, or a portion thereof, by compression include water-soluble compressible carbohydrates such as sugars, which include dextrose, sucrose, maltose, and lactose, sugar-alcohols, which include mannitol, sorbitol, maltitol, xylitol, starch hydrolysates, which include dextrins, and maltodextrins, and the like, water insoluble plastically deforming materials such as microcrystalline cellulose or other cellulosic derivatives, water-insoluble brittle fracture materials such as dicalcium phosphate, tricalcium phosphate and the like and mixtures thereof.
  • water-soluble compressible carbohydrates such as sugars, which include dextrose, sucrose, maltose, and lactose
  • sugar-alcohols which include mannitol, sorbitol, maltitol, xylitol
  • starch hydrolysates which include dextrins, and
  • Suitable binders for making the core, or a portion thereof, by compression include dry binders such as polyvinyl pyrrolidone, hydroxypropylmethylcellulose, and the like; wet binders such as water-soluble polymers, including hydrocolloids such as acacia, alginates, agar, guar gum, locust bean, carrageenan, carboxymethylcellulose, tara, gum arabic, tragacanth, pectin, xanthan, gellan, gelatin, maltodextrin, galactomannan, pusstulan, laminarin, scleroglucan, inulin, whelan, rhamsan, zooglan, methylan, chitin, cyclodextrin, chitosan, polyvinyl pyrrolidone, cellulosics, sucrose, starches, and the like; and derivatives and mixtures thereof.
  • dry binders such as polyvinyl pyrrol
  • Suitable disintegrants for making the core, or a portion thereof, by compression include sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, starches, microcrystalline cellulose, and the like.
  • Suitable lubricants for making the core, or a portion thereof, by compression include long chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glycerides and waxes.
  • Suitable glidants for making the core, or a portion thereof, by compression include colloidal silicon dioxide, and the like.
  • Suitable release-modifying compressible excipients for making the core, or a portion thereof, by compression include swellable erodible hydrophillic materials, insoluble edible materials, pH-dependent polymers, and the like.
  • Suitable swellable erodible hydrophilic materials for use as release-modifying excipients for making the core, or a portion thereof, by compression include: water swellable cellulose derivatives, polyalkalene glycols, thermoplastic polyalkalene oxides, acrylic polymers, hydrocolloids, clays, gelling starches, and swelling cross-linked polymers, and derivitives, copolymers, and combinations thereof.
  • suitable water swellable cellulose derivatives include sodium carboxymethylcellulose, cross-linked hydroxypropylcellulose, hydroxypropyl cellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyisopropylcellulose, hydroxybutylcellulose,hydroxyphenylcellulose, hydroxyethylcellulose (HEC), hydroxypentylcellulose, hydroxypropylethylcellulose, hydroxypropylbutylcellulose, hydroxypropylethylcellulose.
  • suitable polyalkalene glyclols include polyethylene glycol.
  • suitable thermoplastic polyalkalene oxides include poly (ethylene oxide).
  • acrylic polymers include potassium methacrylatedivinylbenzene copolymer, polymethylmethacrylate, CARBOPOL (high-molceular weight cross-linked acrylic acid homopolymers and copolymers), and the like.
  • suitable hydrocolloids include alginates, agar, guar gum, locust bean gum, kappa carrageenan, iota carrageenan, tara, gum arabic, tragacanth, pectin, xanthan gum, gellan gum, maltodextrin, galactomannan, pusstulan, laminarin, scleroglucan, gum arabic, inulin, pectin, gelatin, whelan, rhamsan, zooglan, methylan, chitin, cyclodextrin, chitosan.
  • Suitable clays include smectites such as bentonite, kaolin, and laponite; magnesium trisilicate, magnesium aluminum silicate, and the like, and derivatives and mixtures thereof.
  • suitable gelling starches include acid hydrolyzed starches, swelling starches such as sodium starch glycolate, and derivatives thereof.
  • suitable swelling cross-linked polymers include cross-linked polyvinyl pyrrolidone, cross-linked agar, and cross-linked carboxymethylcellose sodium.
  • Suitable insoluble edible materials for use as release-modifying excipients for making the core, or a portion thereof, by compression include water-insoluble polymers, and low-melting hydrophobic materials.
  • suitable water-insoluble polymers include ethylcellulose, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose acetate and its derivatives, acrylates, methacrylates, acrylic acid copolymers; and the like and derivatives, copolymers, and combinations thereof.
  • Suitable low-melting hydrophobic materials include fats, fatty acid esters, phospholipids, and waxes.
  • suitable fats include hydrogenated vegetable oils such as for example cocoa butter, hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenated sunflower oil, and hydrogenated soybean oil; and free fatty acids and their salts.
  • suitable fatty acid esters include sucrose fatty acid esters, mono, di, and triglycerides, glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl tristearate, glyceryl trilaurylate, glyceryl myristate, Glyco Wax-932, lauroyl macrogol-32 glycerides, and stearoyl macrogol-32 glycerides.
  • Suitable phospholipids include phosphotidyl choline, phosphotidyl serene, phosphotidyl enositol, and phosphotidic acid.
  • suitable waxes include camauba wax, spermaceti wax, beeswax, candelilla wax, shellac wax, microcrystalline wax, and paraffin wax; fat-containing mixtures such as chocolate; and the like.
  • Suitable pH-dependent polymers for use as release-modifying excipients for making the core, or a portion thereof, by compression include enteric cellulose derivatives, for example hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate; natural resins such as shellac and zein; enteric acetate derivatives such as for example polyvinylacetate phthalate, cellulose acetate phthalate, acetaldehyde dimethylcellulose acetate; and enteric acrylate derivatives such as for example polymethacrylate-based polymers such as poly(methacrylic acid, methyl methacrylate) 1:2, which is commercially available from Rohm Pharma GmbH under the tradename EUDRAGIT S, and poly(methacrylic acid, methyl methacrylate) 1:1, which is commercially available from Rohm Pharma GmbH under the tradename EUDRAGIT L, and the like, and derivatives, salts, copolymers, and combinations thereof.
  • Suitable pharmaceutically acceptable adjuvants for making the core, or a portion thereof, by compression include, preservatives; high intensity sweeteners such as aspartame, acesulfame potassium, sucralose, and saccharin; flavorants; colorants; antioxidants; surfactants; wetting agents; and the like and mixtures thereof.
  • the core is prepared by the compression methods and apparatus described in copending U.S. patent application Ser. No. 09/966,509, pages 16-27, the disclosure of which is incorporated herein by reference.
  • the core is made using a rotary compression module comprising a fill zone, insertion zone, compression zone, ejection zone, and purge zone in a single apparatus having a double row die construction as shown in FIG. 6 of U.S. patent application Ser. No. 09/966,509.
  • the dies of the compression module are preferably filled using the assistance of a vacuum, with filters located in or near each die.
  • the purge zone of the compression module includes an optional powder recovery system to recover excess powder from the filters and return the powder to the dies.
  • the core, or the shell, or a portion thereof is prepared by molding.
  • the core, or the shell, or a portion thereof is made from a flowable material.
  • the flowable material may be any edible material that is flowable at a temperature between about 37° C. and 250° C., and that is solid, semi-solid, or can form a gel at a temperature between about ⁇ 10° C. and about 35° C.
  • the flowable material may comprise a dissolved or molten component, and optionally a solvent such as for example water or organic solvents, or combinations thereof. The solvent may be partially or substantially removed by drying.
  • Suitable flowable materials for making the core, or the shell, or a portion thereof by molding include those comprising thermoplastic materials; film formers; thickeners such as gelling polymers or hydrocolloids; low melting hydrophobic materials such as fats and waxes; non-crystallizable carbohydrates; and the like.
  • Suitable molten components of the flowable material include thermoplastic materials, low melting hydrophobic materials, and the like.
  • Suitable dissolved components for the flowable material include film formers, thickeners such as gelling polymers or hydrocolloids, non-crystallizable carbohydrates, and the like.
  • Suitable thermoplastic materials can be molded and shaped when heated, and include both water soluble and water insoluble polymers that are generally linear, not crosslinked, nor strongly hydrogen bonded to adjacent polymer chains.
  • suitable thermoplastic materials include: thermoplastic water swellable cellulose derivatives, thermoplastic water insoluble cellulose derivatrives, thermoplastic vinyl polymers, thermoplastic starches, thermplastic polyalkalene glycols, thermoplastic polyalkalene oxides, and amorphous sugar-glass, and the like, and derivatives, copolymers, and combinations thereof.
  • suitable thermoplastic water swellable cellulose derivatives include hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC).
  • thermoplastic water insoluble cellulose derivatrives examples include cellulose acetate (CA), ethyl cellulose (EC), cellulose acetate butyrate (CAB), cellulose propionate.
  • suitable thermoplastic vinyl polymers include polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP).
  • suitable thermoplastic starches are disclosed for example in U.S. Pat. No. 5,427,614.
  • suitable thermoplastic polyalkalene glycols include polyethylene glycol.
  • suitable thermoplastic polyalkalene oxides include polyethylene oxide having a molecular weight from about 100,000 to about 900,000 Daltons.
  • Other suitable thermoplastic materials include sugar in the form on an amorphous glass such as that used to make hard candy forms.
  • any film former known in the art is suitable for use in the flowable material of the present invention.
  • suitable film formers include, but are not limited to, film-forming water soluble polymers, film-forming proteins, film-forming water insoluble polymers, and film-forming pH-dependent polymers.
  • the film-former for making the core or shell or portion thereof by molding may be selected from cellulose acetate, ammonio methacrylate copolymer type B, shellac, hydroxypropylmethylcellulose, and polyethylene oxide, and combinations thereof.
  • Suitable film-forming water soluble polymers include water soluble vinyl polymers such as polyvinylalcohol (PVA); water soluble polycarbohydrates such as hydroxypropyl starch, hydroxyethyl starch, pullulan, methylethyl starch, carboxymethyl starch, pre-gelatinized starches, and film-forming modified starches; water swellable cellulose derivatives such as hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), hydroxyethylmethylcellulose (HEMC), hydroxybutylmethylcellulose (HBMC), hydroxyethylethylcellulose (HEEC), and hydroxyethylhydroxypropylmethyl cellulose (HEMPMC); water soluble copolymers such as methacrylic acid and methacrylate ester copolymers, polyvinyl alcohol and polyethylene glycol copolymers, polyethylene oxide and polyvinylpyrrolidone copolymers; and derivatives such as
  • Suitable film-forming proteins may be natural or chemically modified, and include gelatin, whey protein, myofibrillar proteins, coaggulatable proteins such as albumin, casein, caseinates and casein isolates, soy protein and soy protein isolates, zein; and polymers, derivatives and mixtures thereof.
  • Suitable film-forming water insoluble polymers include for example ethylcellulose, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose acetate and its derivatives, acrylates, methacrylates, acrylic acid copolymers; and the like and derivatives, copolymers, and combinations thereof.
  • Suitable film-forming pH-dependent polymers include enteric cellulose derivatives, such as for example hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate; natural resins, such as shellac and zein; enteric acetate derivatives such as for example polyvinylacetate phthalate, cellulose acetate phthalate, acetaldehyde dimethylcellulose acetate; and enteric acrylate derivatives such as for example polymethacrylate-based polymers such as poly(methacrylic acid, methyl methacrylate) 1:2, which is commercially available from Rohm Pharma GmbH under the tradename, EUDRAGIT S, and poly(methacrylic acid, methyl methacrylate) 1:1, which is commercially available from Rohm Pharma GmbH under the tradename, EUDRAGIT L, and the like, and derivatives, salts, copolymers, and combinations thereof.
  • enteric cellulose derivatives such as for example hydroxypropyl methylcellulose
  • HPMC 2910 is a cellulose ether having a degree of substitution of about 1.9 and a hydroxypropyl molar substitution of 0.23, and containing, based upon the total weight of the compound, from about 29% to about 30% methoxyl groups and from about 7% to about 12% hydroxylpropyl groups.
  • HPMC 2910 is commercially available from the Dow Chemical Company under the tradename METHOCEL E.
  • METHOCEL E5 which is one grade of HPMC-2910 suitable for use in the present invention, has a viscosity of about 4 to 6 cps (4 to 6 millipascal-seconds) at 20° C.
  • METHOCEL E6 which is another grade of HPMC-2910 suitable for use in the present invention, has a viscosity of about 5 to 7 cps (5 to 7 millipascal-seconds) at 20° C. in a 2% aqueous solution as determined by a Ubbelohde viscometer.
  • METHOCEL E15 which is another grade of HPMC-2910 suitable for use in the present invention, has a viscosity of about 15000 cps (15 millipascal-seconds) at 20° C. in a 2% aqueous solution as determined by a Ubbelohde viscometer.
  • degree of substitution shall mean the average number of substituent groups attached to a anhydroglucose ring
  • hydroxypropyl molar substitution shall mean the number of moles of hydroxypropyl per mole anhydroglucose.
  • polyvinyl alcohol and polyethylene glycol copolymer are commercially available from BASF Corporation under the tradename KOLLICOAT IR.
  • modified starches include starches that have been modified by crosslinking, chemically modified for improved stability or optimized performance, or physically modified for improved solubility properties or optimized performance.
  • chemically-modified starches are well known in the art and typically include those starches that have been chemically treated to cause replacement of some of its hydroxyl groups with either ester or ether groups.
  • Crosslinking as used herein, may occur in modified starches when two hydroxyl groups on neighboring starch molecules are chemically linked.
  • pre-gelatinized starches or “instantized starches” refers to modified starches that have been pre-wetted, then dried to enhance their cold-water solubility.
  • Suitable modified starches are commercially available from several suppliers such as, for example, A. E. Staley Manufacturing Company, and National Starch & Chemical Company.
  • One suitable film forming modified starch includes the pre-gelatinized waxy maize derivative starches that are commercially available from National Starch & Chemical Company under the tradenames PURITY GUM and FILMSET, and derivatives, copolymers, and mixtures thereof
  • Such waxy maize starches typically contain, based upon the total weight of the starch, from about 0 percent to about 18 percent of amylose and from about 100% to about 88% of amylopectin.
  • Another suitable film forming modified starch includes the hydroxypropylated starches, in which some of the hydroxyl groups of the starch have been etherified with hydroxypropyl groups, usually via treatment with propylene oxide.
  • hydroxypropyl starch that possesses film-forming properties is available from Grain Processing Company under the tradename, PURE-COTE B790.
  • Suitable tapioca dextrins for use as film formers include those available from National Starch & Chemical Company under the tradenames CRYSTAL GUM or K-4484, and derivatives thereof such as modified food starch derived from tapioca, which is available from National Starch and Chemical under the tradename PURITY GUM 40, and copolymers and mixtures thereof.
  • any thickener known in the art is suitable for use in the flowable material of the present invention.
  • thickeners include but are not limited to hydrocolloids (also referred to herein as gelling polymers), clays, gelling starches, and crystallizable carbohydrates, and derivatives, copolymers and mixtures thereof.
  • hydrocolloids also referred to herein as gelling polymers
  • suitable hydrocolloids such as alginates, agar, guar gum, locust bean, carrageenan, tara, gum arabic, tragacanth, pectin, xanthan, gellan, maltodextrin, galactomannan, pusstulan, laminarin, scleroglucan, gum arabic, inulin, pectin, whelan, rhamsan, zooglan, methylan, chitin, cyclodextrin, chitosan.
  • Suitable clays include smectites such as bentonite, kaolin, and laponite; magnesium trisilicate, magnesium aluminum silicate, and the like, and derivatives and mixtures thereof.
  • suitable gelling starches include acid hydrolyzed starches, and derivatives and mixtures thereof.
  • Additional suitable thickening hydrocolloids include low-moisture polymer solutions such as mixtures of gelatin and other hydrocolloids at water contents up to about 30%, such as for example those used to make “gummi” confection forms.
  • Suitable thickeners include crystallizable carbohydrates, and the like, and derivatives and combinations thereof.
  • Suitable crystallizable carbohydrates include the monosaccharides and the oligosaccharides.
  • the aldohexoses e.g., the D and L isomers of allose, altrose, glucose, mannose, gulose, idose, galactose, talose
  • the ketohexoses e.g., the D and L isomers of fructose and sorbose along with their hydrogenated analogs: e.g., glucitol (sorbitol), and mannitol are preferred.
  • the 1,2-disaccharides sucrose and trehalose the 1,4-disaccharides maltose, lactose, and cellobiose, and the 1,6-disaccharides gentiobiose and melibiose, as well as the trisaccharide raffinose are preferred along with the isomerized form of sucrose known as isomaltulose and its hydrogenated analog isomalt.
  • Other hydrogenated forms of reducing disaccharides such as maltose and lactose
  • maltitol and lactitol are also preferred.
  • the hydrogenated forms of the aldopentoses e.g., D and L ribose, arabinose, xylose, and lyxose and the hydrogenated forms of the aldotetroses: e.g., D and L erythrose and threose are preferred and are exemplified by xylitol and erythritol, respectively.
  • the flowable material comprises gelatin as a gelling polymer.
  • Gelatin is a natural, thermogelling polymer. It is a tasteless and colorless mixture of derived proteins of the albuminous class which is ordinarily soluble in warm water.
  • Type A gelatin is a derivative of acid-treated raw materials.
  • Type B gelatin is a derivative of alkali-treated raw materials.
  • Bloom is defined as the weight in grams required to move a half-inch diameter plastic plunger 4 mm into a 6.67% gelatin gel that has been held at 10° C. for 17 hours.
  • the flowable material is an aqueous solution comprising 20% 275 Bloom pork skin gelatin, 20% 250 Bloom Bone Gelatin, and approximately 60% water.
  • Suitable xanthan gums include those available from C. P. Kelco Company under the tradenames KELTROL 1000, XANTROL 180, or K9B310.
  • Suitable clays include smectites such as bentonite, kaolin, and laponite; magnesium trisilicate, magnesium aluminum silicate, and the like, and derivatives and mixtures thereof.
  • Acid-hydrolyzed starch is one type of modified starch that results from treating a starch suspension with dilute acid at a temperature below the gelatinization point of the starch. During the acid hydrolysis, the granular form of the starch is maintained in the starch suspension, and the hydrolysis reaction is ended by neutralization, filtration and drying once the desired degree of hydrolysis is reached. As a result, the average molecular size of the starch polymers is reduced. Acid-hydrolyzed starches (also known as “thin boiling starches”) tend to have a much lower hot viscosity than the same native starch as well as a strong tendency to gel when cooled.
  • Gelling starches include those starches that, when combined with water and heated to a temperature sufficient to form a solution, thereafter form a gel upon cooling to a temperature below the gelation point of the starch.
  • Examples of gelling starches include, but are not limited to, acid hydrolyzed starches such as that available from Grain Processing Corporation under the tradename PURE-SET B950; hydroxypropyl distarch phosphate such as that available from Grain Processing Corporation under the tradename, PURE-GEL B990, and mixtures thereof.
  • Suitable low-melting hydrophobic materials include fats, fatty acid esters, phospholipids, and waxes.
  • suitable fats include hydrogenated vegetable oils such as for example cocoa butter, hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenated sunflower oil, and hydrogenated soybean oil; and free fatty acids and their salts.
  • Suitable fatty acid esters include sucrose fatty acid esters, mono, di, and triglycerides, glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl tristearate, glyceryl trilaurylate, glyceryl myristate, Glyco Wax-932, lauroyl macrogol-32 glycerides, and stearoyl macrogol-32 glycerides.
  • suitable phospholipids include phosphotidyl choline, phosphotidyl serene, phosphotidyl enositol, and phosphotidic acid.
  • suitable waxes include carnauba wax, spermaceti wax, beeswax, candelilla wax, shellac wax, microcrystalline wax, and paraffin wax; fat-containing mixtures such as chocolate; and the like.
  • Suitable non-crystallizable carbohydrates include non-crystallizable sugars such as polydextrose, and starch hydrolysates, e.g. glucose syrup, corn syrup, and high fructose corn syrup; and non-crystallizable sugar-alcohols such as maltitol syrup.
  • Suitable solvents for optional use as components of the flowable material for making the core, or the shell, or a portion thereof by molding include water; polar organic solvents such as methanol, ethanol, isopropanol, acetone, and the like; and non-polar organic solvents such as methylene chloride, and the like; and mixtures thereof.
  • the flowable material for making the core or the shell or a portion thereof by molding may optionally comprise adjuvants or excipients, which may comprise up to about 30% by weight of the flowable material.
  • adjuvants or excipients include plasticizers, detackifiers, humectants, surfactants, anti-foaming agents, colorants, flavorants, sweeteners, opacifiers, and the like.
  • Suitable plasticizers for making the core, the shell, or a portion thereof, by molding include, but not be limited to polyethylene glycol; propylene glycol; glycerin; sorbitol; triethyl citrate; tribuyl citrate; dibutyl sebecate; vegetable oils such as castor oil, rape oil, olive oil, and sesame oil; surfactants such as polysorbates, sodium lauryl sulfates, and dioctyl-sodium sulfosuccinates; mono acetate of glycerol; diacetate of glycerol; triacetate of glycerol; natural gums; triacetin; acetyltributyl citrate; diethyloxalate; diethylmalate; diethyl fumarate; diethylmalonate; dioctylphthalate; dibutylsuccinate; glyceroltributyrate; hydrogenated castor oil; fatty acids
  • the flowable material comprises less than 5% humectants, or alternately is substantially free of humectants, such as glycerin, sorbitol, maltitol, xylitol, or propylene glycol.
  • Humectants have traditionally been included in pre-formed films employed in enrobing processes, such as that disclosed in U.S. Pat. Nos. 5,146,730 and 5,459,983, assigned to Banner Gelatin Products Corp., in order to ensure adequate flexibility or plasticity and bondability of the film during processing. Humectants function by binding water and retaining it in the film. Pre-formed films used in enrobing processes can typically comprise up to 45% water. Disadvantageously, the presence of humectant prolongs the drying process, and can adversely affect the stability of the finished dosage form.
  • the core, the shell, or portions thereof may be molded using a solvent-free process.
  • the core may comprise active ingredient contained within an excipient matrix.
  • the matrix, or the core, or the shell, or portions thereof typically comprises at least about 30 percent, e.g. at least about 45 weight percent of a thermal-reversible carrier, and optionally up to about 30 weight percent of various adjuvants such as for example plasticizers, gelling agents, strengthening agents, colorants, stabilizers, preservatives, and the like as known in the art.
  • the matrix or the core, or the shell, or portions thereof may optionally further comprise up to about 55 weight percent of one or more release-modifying moldable excipients as described below.
  • the core may be in a variety of different shapes.
  • the core may be shaped as a polyhedron, such as a cube, pyramid, prism, or the like; or may have the geometry of a space figure with some non-flat faces, such as a cone, truncated cone, cylinder, sphere, torus, or the like.
  • the core has one or more major faces.
  • the core surface typically has two opposing major faces formed by contact with the upper and lower punch faces in the compression machine.
  • the core surface typically further comprises a “belly-band” located between the two major faces, and formed by contact with the die walls in the compression machine.
  • Exemplary core shapes which may be employed include tablet shapes formed from compression tooling shapes described by “The Elizabeth Companies Tablet Design Training Manual” (Elizabeth Carbide Die Co., Inc., p. 7 (McKeesport, Pa.) (incorporated herein by reference) as follows (the tablet shape corresponds inversely to the shape of the compression tooling): 1. Shallow Concave. 2. Standard Concave. 3. Deep Concave. 4. Extra Deep Concave. 5. Modified Ball Concave. 6. Standard Concave Bisect. 7. Standard Concave Double Bisect. 8. Standard Concave European Bisect. 9. Standard Concave Partial Bisect. 10. Double Radius. 11. Bevel & Concave. 12. Flat Plain. 13.
  • the core comprises multiple portions, for example a first portion and a second portion.
  • the portions may be prepared by the same or different methods and mated using various techniques, such as the thermal cycle molding and thermal setting molding methods described herein.
  • the first and second portions may both be made by compression, or both may be made by molding.
  • one portion may be made by compression and the other by molding.
  • the same or different active ingredient may be present in the first and second portions of the core.
  • one or more core portions may be substantially free of active ingredients.
  • the core or a portion thereof may function to confer modified release properties to at least one active ingredient contained therein.
  • the core or core portion is made by compression, as previously noted, the core preferably comprises a release-modifying compressible excipient.
  • the core or core portion is made by molding, as previously noted, the core preferably comprises a release-modifying moldable excipient.
  • the core portion preferably comprises a release-modifying compressible or moldable excipient selected from swellable erodible hydrophilic agents, pH-dependent polymers, and combinations thereof.
  • the core portion preferably comprises a release-modifying excipient selected from combinations of insoluble edible materials and pore formers.
  • the thermal-reversible carrier may function by dissolving and forming pores or channels through which the active ingredient may be liberated.
  • the shell of the present invention comprises and first shell portion and a second shell portion that are compositionally different.
  • the first and second shell portions may comprise different ingredients, or the first and second shell portions may comprise different levels of the same ingredients, e.g. colorants, opacifiers, film-formers, etc.
  • the first and second shell portions may be visually distinct from one another, for example the visually distinct portions may be of different colors, hues, glosses, reflective qualities, brightness, depth, shades, chroma, opacity, etc.
  • the shell may have a red portion and a yellow portion, or a flat finish portion and a glossy portion, or an opaque portion and a translucent portion.
  • the first and second shell portions may have different thickness.
  • the first and second shell portions may have different functionalities.
  • the first and second shell portions may confer different release properties to an active ingredient contained in either the subject shell portion, or in a corresponding underlying core portion.
  • the first shell portion may function as a diffusional membrane which contains pores through which fluids can enter the dosage form, and dissolved active ingredient can be released from an underlying core portion; and the second shell portion, may function as an eroding matrix from which active ingredient dispersed in the second shell portion is liberated by the dissolution of successive layers of the shell portion surface.
  • the shell portions of the present invention may be prepared by molding, using a solvent-free process, or a solvent-based process, and depending on the method used, typically comprise a variety of excipients which are useful for conferring desired properties to the shell portions.
  • the shell portions may optionally further comprise one or more active ingredients.
  • the shell portion or portions are prepared using a solvent-free molding process
  • the shell will typically comprise at least about 30 percent, e.g. at least about 45 percent by weight of a thermal-reversible carrier.
  • the shell portion or portions may optionally further comprise up to about 55 weight percent of a release-modifying excipient.
  • the shell portion or portions may optionally further comprise up to about 30 weight percent total of various plasticizers, adjuvants and excipients.
  • the release modifying excipient is preferrably selected from swellable, erodible hydrophilic materials.
  • the shell portion or portions will typically comprise at least about 10 weight percent, e.g. at least about 12 weight percent or at least about 15 weight percent or at least about 20 weight percent or at least about 25 weight percent of a film-former.
  • the solvent-molded shell portion or portions may optionally further comprise up to about 55 weight percent of a release-modifying excipient.
  • the solvent-molded shell portion or portions may again also optionally further comprise up to about 30 weight percent total of various plasticizers, adjuvants, and excipients.
  • the shell portion or portions of the present invention are substantially free of pores having a diameter of 0.5-5.0 microns.
  • substantially free means that the shell portion or portions have a pore volume of less than about 0.02 cc/g, preferably less than about 0.01 cc/g, more preferably less than about 0.005 cc/g in the pore diameter range of 0.5 to 5.0 microns.
  • typical compressed materials have pore volumes of more than about 0.02 cc/g in this diameter range.
  • the core is a molded core and the core or core portions are substantially free of pores having a diameter of 0.5-5.0 microns.
  • the pore volume, pore diameter and density of the shell portions of this invention may be determined using a Quantachrome Instruments PoreMaster 60 mercury intrusion porosimeter and associated computer software program known as “Porowin.” The procedure is documented in the Quantachrome Instruments PoreMaster Operation Manual.
  • the PoreMaster determines both pore volume and pore diameter of a solid or powder by forced intrusion of a non-wetting liquid (mercury), which involves evacuation of the sample in a sample cell (penetrometer), filling the cell with mercury to surround the sample with mercury, applying pressure to the sample cell by: (i) compressed air (up to 50 psi maximum); and (ii) a hydraulic (oil) pressure generator (up to 60000 psi maximum).
  • Intruded volume is measured by a change in the capacitance as mercury moves from outside the sample into its pores under applied pressure.
  • High pressure fluid (Dila AX, available from Shell Chemical Co.).
  • Fine Evacuation time 1 min.
  • the cell (filled with mercury) is then removed and weighed.
  • the cell is then emptied into the mercury reservoir, and two tablets from each sample are placed in the cell and the cell is reassembled.
  • the weight of the cell and sample are then recorded.
  • the cell is then installed in the low-pressure station, the low-pressure option is selected from the menu, and the following parameters are set:
  • the shell portion or portions of the present invention typically has a surface gloss of at least about 150 gloss units, e.g. at least about 175 gloss units, or at least about 190 gloss units, when measured according to the method set forth below.
  • typical sprayed coatings have gloss values of less than about 150 gloss units. Dosage forms with high surface gloss are preferred by consumers due to their aesthetic elegance and perceived swallowability.
  • the surface gloss of the shell depends upon a number of factors, including the shell composition, the method of forming the shell, and, if a mold is used, the surface finish on the mold.
  • Shell or shell portions may be tested for surface gloss using an instrument available from TriCor Systems Inc. (Elgin, Ill.) under the tradename TRI-COR MODEL 805A/806H SURFACE ANALYSIS SYSTEM and generally in accordance with the procedure described in “TriCor Systems WGLOSS 3.4 Model 805A/806H Surface Analysis System Reference Manual” (1996), which is incorporated by reference herein, except as modified below.
  • TriCor Systems Inc. Elgin, Ill.
  • TRI-COR MODEL 805A/806H SURFACE ANALYSIS SYSTEM and generally in accordance with the procedure described in “TriCor Systems WGLOSS 3.4 Model 805A/806H Surface Analysis System Reference Manual” (1996), which is incorporated by reference herein, except as modified below.
  • This instrument uses a CCD camera detector, a flat diffuse light source, compares tablet samples to a reference standard, and determines average gloss values at a 60 degree incident angle. During its operation, the instrument generates a gray-scale image, wherein the occurrence of brighter pixels indicates the presence of more gloss at that given location.
  • the instrument also incorporates software that uses a grouping method to quantify gloss: i.e., pixels with similar brightness which are grouped together for averaging purposes.
  • the “percent full scale” or “percent ideal” setting (also referred to as the “percent sample group” setting), is specified by the user to designate the portion of the brightest pixels above the threshold that will be considered as one group and averaged within that group.
  • “Threshold,” as used herein, is defined as the maximum gloss value that will not be included in the average gloss value calculation. Thus, the background, or the non-glossy areas of a sample are excluded from the average gloss value calculations.
  • the method disclosed in K. Fegley and C. Vesey, “The Effect of Tablet Shape on the Perception of High Gloss Film Coating Systems,” which is available at www.colorcon.com as of Mar. 18, 2002 and incorporated by reference herein, is used to minimize the effects resulting from different tablet shapes, and to report a metric that was comparable across the industry. (The 50% sample group setting is selected as the setting which best approximates analogous data from tablet surface roughness measurements.)
  • a standard surface gloss measurement is created.
  • a standard surface gloss was obtained using gel-coated caplets available from McNEIL-PPC, Inc. under the tradename, EXTRA STRENGTH TYLENOL GELCAPS. The average gloss value for a sample of 112 of such gel-coated caplets was then determined, while employing the 25 mm full view mask (190-280), and configuring the instrument to the following settings:
  • the total weight of the shell portion or portions is preferably about 20 percent to about 400 percent of the weight of the core.
  • the total weight of the shell portion or portions is typically from about 50 percent to about 400 percent, e.g. from about 75 percent to about 400 percent, or about 100 percent to about 200 percent of the weight of the core.
  • the total weight of the shell portion or portions is typically from about 20 percent to about 100 percent of the weight of the core.
  • Typical shell portion thicknesses which may be employed in this invention are about 50 to about 4000 microns. In certain preferred embodiments, the shell has a thickness of less than 800 microns. In embodiments wherein the shell portion is prepared by a solvent-free molding process, the shell portion typically has a thickness of about 500 to about 4000 microns, e.g. about 500 to about 2000 microns, say about 500 to about 800 microns, or about 800 to about 1200 microns. In embodiments wherein the shell portion is prepared by a solvent-based molding process, the shell portion typically has a thickness of less than about 800 microns, e.g. about 100 to about 600 microns, say about 150 to about 400 microns.
  • the dosage form comprises first and second core portions and first and second shell portions, and at least one of the shell portions has a thickness of less than about 800 microns, e.g. about 100 to about 600 microns, e.g. about 150 to about 400 microns
  • Suitable thermal-reversible carriers for making the core, or the shell, or a portion thereof, by molding are thermoplastic materials typically having a melting point below about 110° C., more preferably between about 20 and about 100° C.
  • suitable thermal-reversible carriers for solvent-free molding include thermplastic polyalkalene glycols, thermoplastic polyalkalene oxides, low melting hydrophobic materials, thermoplastic polymers, thermoplastic starches, and the like.
  • Preferred thermal-reversible carriers include polyethylene glycol and polyethylene oxide.
  • Suitable thermoplastic polyalkylene glycols for use as thermal-reversible carriers include polyethylene glycol having molecular weight from about 100 to about 20,000, e.g. from about 100 to about 8,000 Daltons.
  • Suitable thermoplastic polyalkalene oxides include polyethylene oxide having a molecular weight from about 100,000 to about 900,000 Daltons.
  • Suitable low-melting hydrophobic materials for use as thermal-reversible carriers include fats, fatty acid esters, phospholipids, and waxes which are solid at room temperature, fat-containing mixtures such as chocolate; and the like.
  • suitable fats include hydrogenated vegetable oils such as for example cocoa butter, hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenated sunflower oil, and hydrogenated soybean oil; and free fatty acids and their salts.
  • Suitable fatty acid esters include sucrose fatty acid esters, mono, di, and triglycerides, glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl tristearate, glyceryl trilaurylate, glyceryl myristate, Glyco Wax-932, lauroyl macrogol-32 glycerides, and stearoyl macrogol-32 glycerides.
  • suitable phospholipids include phosphotidyl choline, phosphotidyl serene, phosphotidyl enositol, and phosphotidic acid.
  • suitable waxes which are solid at room temperature include carnauba wax, spermaceti wax, beeswax, candelilla wax, shellac wax, microcrystalline wax, and paraffin wax.
  • suitable thermoplastic polymers for use as thermal-reversible carriers include thermoplastic water swellable cellulose derivatives, thermoplastic water insoluble polymers, thermoplastic vinyl polymers, thermoplastic starches, and thermoplastic resins, and combinations thereof.
  • Suitable thermoplastic water swellable cellulose derivatives include include hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), carboxymethylcellulose (CMC), cross-linked hydroxypropylcellulose, hydroxypropyl cellulose (HPC), hydroxybutylcellulose (HBC), hydroxyethylcellulose (HEC), hydroxypropylethylcellulose, hydroxypropylbutylcellulose, hydroxypropylethylcellulose, and salts, derivatives, copolymers, and combinations thereof.
  • HPMC hydroxypropylmethyl cellulose
  • MC methyl cellulose
  • CMC carboxymethylcellulose
  • HPC hydroxypropyl cellulose
  • HBC hydroxybutylcellulose
  • HEC hydroxyethylcellulose
  • thermoplastic water insoluble polymers include ethylcellulose, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose acetate and its derivatives, acrylates, methacrylates, acrylic acid copolymers, and the like and derivatives, copolymers, and combinations thereof.
  • Suitable thermoplastic vinyl polymers include polyvinylacetate, polyvinyl alcohol, and polyvinyl pyrrolidone (PVP). Examples of suitable thermoplastic starches for use as thermal-reversible carriers are disclosed for example in U.S. Pat. No. 5,427,614. ______.
  • thermoplastic resins for use as themal-reversible carriers include dammars, mastic, rosin, shellac, sandarac, and glcerol ester of rosin.
  • the thermal-reversible carrier for making the core, or a portion thereof, by molding is selected from polyalkylene glycols, polyalkaline oxides, and combinations thereof.
  • Suitable release-modifying excipients for making the core, or the shell, or a portion thereof, by solvent free or solvent based molding include but are not limited to swellable erodible hydrophilic materials, pH-dependent polymers, pore formers, and insoluble edible materials.
  • suitable release-modifying excipients for making the core, or the shell, or a portion thereof, by molding include hydroxypropylmethylcellulose, polyethylene oxide, ammonio methacrylate copolymer type B, and shellac, and combinations thereof.
  • Suitable swellable erodible hydrophilic materials for use as release-modifying excipients for making the core, or the shell, or a portion thereof by a solvent-free molding process include water swellable cellulose derivatives, polyalkalene glycols, thermoplastic polyalkalene oxides, acrylic polymers, hydrocolloids, clays, gelling starches, and swelling cross-linked polymers, and derivitives, copolymers, and combinations thereof.
  • suitable water swellable cellulose derivatives include sodium carboxymethylcellulose, cross-linked hydroxypropylcellulose, hydroxypropyl cellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyisopropylcellulose, hydroxybutylcellulose,hydroxyphenylcellulose, hydroxyethylcellulose (HEC), hydroxypentylcellulose, hydroxypropylethylcellulose, hydroxypropylbutylcellulose, hydroxypropylethylcellulose.
  • suitable polyalkalene glyclols include polyethylene glycol.
  • suitable thermoplastic polyalkalene oxides include poly (ethylene oxide).
  • acrylic polymers include potassium methacrylatedivinylbenzene copolymer, polymethylmethacrylate, CARBOPOL (high-molceular weight cross-linked acrylic acid homopolymers and copolymers), and the like.
  • suitable hydrocolloids include alginates, agar, guar gum, locust bean gum, kappa carrageenan, iota carrageenan, tara, gum arabic, tragacanth, pectin, xanthan gum, gellan gum, maltodextrin, galactomannan, pusstulan, laminarin, scleroglucan, gum arabic, inulin, pectin, gelatin, whelan, rhamsan, zooglan, methylan, chitin, cyclodextrin, chitosan.
  • Suitable clays include smectites such as bentonite, kaolin, and laponite; magnesium trisilicate, magnesium aluminum silicate, and the like, and derivatives and mixtures thereof.
  • suitable gelling starches include acid hydrolyzed starches, swelling starches such as sodium starch glycolate, and derivatives thereof.
  • suitable swelling cross-linked polymers include cross-linked polyvinyl pyrrolidone, cross-linked agar, and cross-linked carboxymethylcellose sodium.
  • Suitable pH-dependent polymers for use as release-modifying moldable excipients for making the molded matrix or molded core or molded shell or a portion thereof by molding include enteric cellulose derivatives, for example hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate; natural resins such as shellac and zein; enteric acetate derivatives such as for example polyvinylacetate phthalate, cellulose acetate phthalate, acetaldehyde dimethylcellulose acetate; and enteric acrylate derivatives such as for example polymethacrylate-based polymers such as poly(methacrylic acid, methyl methacrylate) 1:2, which is commercially available from Rohm Pharma GmbH under the tradename EUDRAGIT S, and poly(methacrylic acid, methyl methacrylate) 1:1, which is commercially available from Rohm Pharma GmbH under the tradename EUDRAGIT L, and the like, and derivatives, salts, copol
  • Suitable insoluble edible materials for use as release-modifying excipients making the core, or the shell, or a portion thereof by molding include water-insoluble polymers, and low-melting hydrophobic materials.
  • suitable water-insoluble polymers include ethylcellulose, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, cellulose acetate and its derivatives, acrylates, methacrylates, acrylic acid copolymers; and the like and derivatives, copolymers, and combinations thereof.
  • Suitable low-melting hydrophobic materials include fats, fatty acid esters, phospholipids, and waxes.
  • suitable fats include hydrogenated vegetable oils such as for example cocoa butter, hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenated sunflower oil, and hydrogenated soybean oil; and free fatty acids and their salts.
  • suitable fatty acid esters include sucrose fatty acid esters, mono, di, and triglycerides, glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl tristearate, glyceryl trilaurylate, glyceryl myristate, Glyco Wax-932, lauroyl macrogol-32 glycerides, and stearoyl macrogol-32 glycerides.
  • Suitable phospholipids include phosphotidyl choline, phosphotidyl serene, phosphotidyl enositol, and phosphotidic acid.
  • suitable waxes include carnauba wax, spermaceti wax, beeswax, candelilla wax, shellac wax, microcrystalline wax, and paraffin wax; fat-containing mixtures such as chocolate; and the like.
  • Suitable pore formers for use as release-modifying excipients for making the molded matrix, the core, the shell, or a portion thereof by molding include water-soluble organic and inorganic materials.
  • the pore former is hydroxypropylmethylcellulose.
  • suitable water-soluble organic materials include water soluble polymers including water soluble cellulose derivatives such as hydroxypropylmethylcellulose, and hydroxypropylcellulose; water soluble carbohydrates such as sugars, and starches; water soluble polymers such as polyvinylpyrrolidone and polyethylene glycol, and insoluble swelling polymers such as microcrystalline cellulose.
  • suitable water soluble inorganic materials include salts such as sodium chloride and potassium chloride and the like and/or mixtures thereof.
  • the shell portion is preferably prepared via the solvent-free molding method described above.
  • the thermal-reversible carrier is preferably selected from polyethylene glycol with weight average molecular weight from about 1450 to about 20000, polyethylene oxide with weight average molecular weight from about 100,000 to about 900,000, and the like.
  • the shell portion typically comprises at least one release modifying agent as described above.
  • the dosage form may function for example as a multi-compartment, e.g. a four-compartment pulsatile release delivery system.
  • each of the compartments may comprise a dose of the same active ingredient, to be release at a desired time or rate.
  • the corresponding first core portion and first shell portions may comprise a dose of the same first active ingredient to be released at a desired time or rate, while the second core portion and second shell portion may comprise a dose of the same second active ingredient to be released at a desired time or rate.
  • each compartment comprises inactive materials which enable the desired functionality of that particular core portion or shell portion.
  • the dosage form may further comprise a water-impermeable barrier layer between the first and second core portions.
  • the water-impermeable barrier layer may be made by any method, for example compression or molding, and preferably comprises at least one water-insoluble material selected from water-insoluble polymers, insoluble edible materials, pH-dependent polymers, and mixtures thereof.
  • At least one active ingredient contained within the dosage form exhibits a delayed burst release profile.
  • delayed burst release profile it is meant that the release of that particular active ingredient from the dosage form is delayed for a pre-determined time after ingestion by the patient, and the delay period (“lag time”) is followed by prompt (immediate) release of that active ingredient.
  • At least one shell portion of the present invention provides for the delay period and is preferraby substantially free of the active ingredient to be released in a delayed burst manner.
  • the delayed burst active ingredient is typically contained within the corresponding underlying core portion.
  • the core portion may be prepared by compression or molding, and is formulated for immediate release, as is known in the art, so that the core portion is readily soluble upon contact with the dissolution medium.
  • the core portion preferably comprises a disintegrant, and optionally comprises additional excipients such as fillers or thermoplastic materials selected from water-soluble or low-melting materials, and surfactants or wetting agents.
  • additional excipients such as fillers or thermoplastic materials selected from water-soluble or low-melting materials, and surfactants or wetting agents.
  • USP 24 specifies that in pH 5.8 phosphate buffer, using USP apparatus 2 (paddles) at 50 rpm, at least 80% of the acetaminophen contained in the dosage form is released therefrom within 30 minutes after dosing, and for ibuprofen tablets, USP 24 specifies that in pH 7.2 phosphate buffer, using USP apparatus 2 (paddles) at 50 rpm, at least 80% of the ibuprofen contained in the dosage form is released therefrom within 60 minutes after dosing. See USP 24, 2000 Version, 19-20 and 856 (1999).
  • At least one active ingredient contained within the dosage form exhibits a delayed and sustained release profile.
  • delayed then sustained release profile it is meant that the release of that particular active ingredient from the dosage form is delayed for a pre-determined time after ingestion by the patient, and the delay period (“lag time”) is followed by sustained (prolonged, extended, or retarded) release of that active ingredient.
  • At least one shell portion of the present invention provides for the delay period, and is preferraby substantially free of the active ingredient to be released in a delayed then sustained manner.
  • the delayed then sustained release active ingredient is preferrably contained within the corresponding underlying core portion.
  • the core portion may function for example as an eroding matrix or a diffusional matrix, or an osmotic pump.
  • the core portion preferably comprises a release-modifying excipient selected from combinations of insoluble edible materials and pore-formers.
  • the thermal-reversible carrier may function by dissolving and forming pores or channels through which the active ingredient may be liberated.
  • the core portion functions as an eroding matrix from which dispersed active ingredient is liberated in a sustained, extended, prolonged, or retarded manner
  • the core portion preferably comprises a release-modifying compressible or moldable excipient selected from swellable erodible hydrophilic materials, pH-dependent polymers, and combinations thereof.
  • the core portion preferably comprises a release-modifying excipient selected from combinations of insoluble edible materials and pore formers.
  • the thermal-reversible carrier may function by dissolving and forming pores or channels through which the active ingredient may be liberated.
  • the core portion preferably comprises a release-modifying compressible or moldable excipient selected from swellable erodible hydrophilic materials, pH-dependent polymers, insoluble edible materials, and combinations thereof.
  • the overlaying shell portion will typically be breached or dissolved prior to onset of erosion of the underlying core portion, and release of active ingredient therefrom.
  • the release-delaying shell portion preferably comprises a release modifying excipient selected from swellable erodible hydrophilic materials, insoluble edible materials, and combinations thereof.
  • the shell portion preferably comprises a release-modifying compressible or moldable excipient selected from swellable erodible hydrophilic materials, pH-dependent polymers, insoluble edible materials, and combinations thereof.
  • the release-delaying shell portion preferably provides a delay of greater than one hour, for example at least about 3 hours, or at least about 4 hours, or at least about 6 hours, or at least about 12 hours to the onset of dissolution of the active ingredient upon contacting of the dosage form with a liquid medium such as water, gastrointestinal fluid or the like.
  • the delay period is typically controlled by the shell portion thickness, composition, or a combination thereof.
  • the delay period is independent of the pH of the dissolution media or fluid environment. For example, the average lag-time for dissolution of active ingredient in 0.1 N HCl is not substantially different (i.e.
  • the release-delaying shell portion prefarably comprises a release modifying excipient selected from swellable erodible hydrophilic materials, insoluble edible materials, and combinations thereof.
  • the shell portion preferably comprises materials which exhibit rapid dissolution in gastro-intestinal fluids.
  • the immediate release shell portion or portions may comprise readily soluble materials selected from water soluble or water swellable thermoplastic film formers, water soluble or water swellable thickeners, crystallizable and non-crystallizable carbohydrates.
  • suitable water soluble or water swellable thermoplastic film formers may be selected from water swellable cellulose derivatives, thermoplastic starches, polyalkalene glycols, polyalkalene oxides, and amorphous sugar glass, and combinations thereof.
  • suitable film formers may be selected from film forming water soluble polymers such as for example water soluble vinyl polymers, water soluble polycarbohydrates, water swellable cellulose derivatives, and water soluble copolymers; film-forming proteins, and combinations thereof.
  • suitable thickeners may be selected from gelling polymers or hydrocolloids; gelling starches, and crystallizable carbohydrates.
  • suitable non-crystallizable carbohydrates may be selected from polydextrose, starch hydrolysates, and non-crystallizable sugar alcohols.
  • the immediate release shell portion will preferably be breached or dissolved within 30 minutes in 900 ml water or 0.1 N HCl, or phosphate buffer solution at 37° C. with stirring by a USP type 2 (Paddle method) at 50 or 100 rpm.
  • the shell portion or portions additionally comprise at least one active ingredient which may be the same or different than the active ingredient contained in the core.
  • the release-modifying agent in said shell portion preferably comprises a pore-former, and optionally a film-former.
  • the shell portion functions as a diffusional membrane.
  • the dissolution of the active ingredient may follow “diffusion-controlled” release kinetics, as described for example in Example 1 of U.S. Pat. No. 5,286,497.
  • Shell portions which confer sustained, extended, or retarded release and/or function as diffusional membranes can be prepared by a solvent-free method, or a solvent-based method, as described above.
  • the release-modifying agent in said shell portion preferably comprises a swellable erodible hydrophilic material, and may optionally comprise a secondary gelling agent such as for example cross-linked carboxymethylcellulose, cross-linked polyvinylpyrrolidone, or sodium starch glycolate.
  • the release-modifying agent is preferably selected from swellable erodible hydrophilic materials.
  • Shell portions which confer delayed release can be prepared by a solvent-free method, or a solvent-based method, as described above.
  • the shell portion is preferably prepared via a solvent-free molding method, as described above.
  • the thermal-reversible carrier is preferably selected from waxes, such as for example camuba wax, spermaceti wax, beeswax, candelilla wax, shellac wax, microcrystalline wax, and paraffin wax; hydrogenated vegetable oils such as for example cocoa butter, hydrogenated castor oil; other waxy materials such as for example glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl tristearate, glyceryl trilaurylate, glyceryl myristate; thermal-reversible polymers such as for example polycaprolactones and polyvinyl acetate.
  • an impermeable barrier can be formed which consists essentially of the thermal reversible carrier.
  • an additional release-modifying agent is not necessary.
  • the release-modifying agent is preferably selected from water insoluble polymers such as cellulose acetate, acrylates, acrylic acid copolymers, cellulose acetate, cellulose acetate propionate, cellulose acetate propionate, cellulose propionate, cellulose acetate butyrate, cellulose acetate phthalate, acetaldehyde dimethylcellulose acetate, cellulose acetate ethyl carbamate, cellulose acetate methyl carbamate, cellulose acetate diethyl aminoacetate, ethylcellulose, methacrylates, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, and the like, and mixtures thereof.
  • the shell portion may optionally further comprise a liquid carrier such as for example mineral oil, propylene glycol
  • the core, the shell, a core portion, or a shell portion is made by the thermal setting molding method and apparatus described in copending U.S. patent application Ser. No. 09/966,450, pages 57-63, the disclosure of which is incorporated herein by reference.
  • the core, the shell, or a portion thereof is formed by injecting a starting material in flowable form into a molding chamber.
  • the starting material preferably comprises an active ingredient and a thermal setting material at a temperature above the melting point of the thermal setting material but below the decomposition temperature of the active ingredient.
  • the starting material is cooled and solidifies in the molding chamber into a shaped form (i.e., having the shape of the mold).
  • the starting material must be in flowable form.
  • it may comprise solid particles suspended in a molten matrix, for example a polymer matrix.
  • the starting material may be completely molten or in the form of a paste.
  • the starting material may comprise an active ingredient dissolved in a molten material.
  • the starting material may be made by dissolving a solid in a solvent, which solvent is then evaporated from the starting material after it has been molded.
  • the starting material may comprise any edible material which is desirable to incorporate into a shaped form, including active ingredients, nutritionals, vitamins, minerals, flavors, sweeteners, and the like.
  • the starting material comprises an active ingredient and a thermal setting material.
  • the thermal setting material may be any edible material that is flowable at a temperature between about 37 and about 120° C., and that is a solid at a temperature between about 0 and about 35° C.
  • Preferred thermal setting materials include water-soluble polymers such as polyalkylene glycols, polyethylene oxides and derivatives, and sucrose esters; fats such as cocoa butter, hydrogenated vegetable oil such as palm kernel oil, cottonseed oil, sunflower oil, and soybean oil; mono-, di-, and triglycerides, phospholipids, waxes such as camuba wax, spermaceti wax, beeswax, candelilla wax, shellac wax, microcrystalline wax, and paraffin wax; fat-containing mixtures such as chocolate; sugar in the form on an amorphous glass such as that used to make hard candy forms, sugar in a supersaturated solution such as that used to make fondant forms; low-moisture polymer solutions such as mixtures of gelatin and other hydrocolloids at water contents up to about 30% such as those used to make “gummi” confection forms.
  • the thermal setting material is a water-soluble polymer such as polyethylene glycol.
  • the core, the shell, a core portion, or a shell portion is make using the thermal cycle molding method and apparatus described in copending U.S. patent application Ser. No. 09/966,497, pages 27-51, the disclosure of which is also incorporated herein by reference.
  • a thermal cycle molding module having the general configuration shown in FIG. 3 therein is employed.
  • the thermal cycle molding module 200 comprises a rotor 202 around which a plurality of mold units 204 are disposed.
  • the thermal cycle molding module includes a reservoir 206 (see FIG.
  • the thermal cycle molding module is provided with a temperature control system for rapidly heating and cooling the mold units.
  • FIGS. 55 and 56 depict such a temperature control system 600.
  • Dosage forms according to the invention comprising a core within a shell comprising a first shell portion and a second shell portion were prepared as follows.
  • the cores were prepared as follows: a beaker was submersed in a 70° C. water bath (Ret digi-visc; Antal-Direct, Wayne, Pa.). The polyethylene glycol (PEG) was added to the beaker and mixed with a spatula until melted. The shellac powder was screened through a #40 mesh screen, and then added to the molten PEG. The combined ingredients were mixed until all the powder was dispersed. Croscarmellose sodium was added next and the beaker contents were mixed for an additional two minutes. The verapamil HCL pellets were then added, and the contents were mixed for five more minutes. Cores were made by dispensing 620 to 640 mg of the resulting molten mixture into an open stainless steel mold (round, 0.4455 inch diameter) and closing the mold. The finished cores were ejected from the mold.
  • PEG polyethylene glycol
  • the first shell portion was made using the following ingredients: Mg/Dosage Ingredient Trade Name Manufacturer Weight % Form Pseudoephedrine HCl Crystal BASF 30.0 53 PharmaChemikalien GmbH & Co. Ludwigshafen/Rhein. Polyethylene Glycol 3350 Carbowax ® Union Carbide 50.0 89 Corporation, Danbury, CT Polyethylene Oxide (MW Polyox ® WSR N-80 Union Carbide 15.0 27 200,000) Corporation, Danbury, CT Triethyl Citrate Morflex, Inc., 5.0 9 Greensboro, NC
  • the first shell portion material was prepared by first submersing a beaker in a 70° C. water bath (Ret digi-visc; Antal-Direct, Wayne, Pa.). The polyethylene glycol (PEG) was added to the beaker and mixed with a spatula until melted. The triethyl citrate was then added to the molten PEG and the mixture was mixed for one minute. The polyethylene oxide (PEO) was added thereto, and the ingredients were mixed for 10 additional minutes. The pseudoephedrine hydrochloride was added, and the ingredients were mixed for two more minutes. The first shell portion material was provided in flowable form.
  • PEG polyethylene glycol
  • PEO polyethylene oxide
  • the pseudoephedrine hydrochloride was added, and the ingredients were mixed for two more minutes.
  • the second shell portion was made using the following ingredients: Mg/Dosage Ingredient Trade Name Manufacturer Weight % Form Dextromethorphan HBr Roche Chemical 10.0 16 Co., Belvidere, NJ Polyethylene Glycol 3350 Carbowax ® Union Carbide 50.0 77 Corporation, Danbury, CT Polyethylene Oxide (MW Polyox ® WSR N-80 Union Carbide 15.0 23 200,000) Corporation, Danbury, CT Shellac Powder Mantrose-Haeuser 10.0 16 Company, Atteboro, MA Croscarmellose Sodium Ac-Di-Sol ® FMC Corporation, 5.0 8 Newark, DE Triethyl Citrate Morflex, Inc., 10.0 16 Greensboro, NC
  • the second shell portion material was prepared by first submersing a beaker in a 70° C. water bath (Ret digi-visc; Antal-Direct, Wayne, Pa.). PEG was added to the beaker and mixed with a spatula until melted. The shellac powder was screened through a #40 mesh screen, and then added to the molten PEG. The combined ingredients were mixed until all powder was dispersed. The triethyl citrate was added next and the beaker contents were mixed for one minute. PEO was added to the beaker and the mixture was mixed for 10 minutes. Croscarmellose sodium was then added and the contents of the beaker were mixed for two additional minutes. Finally, dextromethorphan HBr was added to the beaker and the ingredients were mixed for two more minutes. The second shell portion material was provided in flowable form.
  • a laboratory scale thermal cycle molding unit was used to apply the first and second shell portions to the cores, and comprised a single mold assembly made from an upper mold assembly portion comprising an upper mold cavity, and a lower mold assembly portion comprising a lower mold cavity.
  • the lower mold assembly portion was first cycled to a hot stage at 85° C. for 30 seconds.
  • the first shell portion material of Example 1 was introduced into the lower mold cavity.
  • a core prepared as described above was then inserted into the cavity.
  • a blank upper mold assembly portion was mated with the lower mold assembly portion.
  • the mold assembly was then cycled to a cold stage at 5° C. for 60 seconds to harden the first shell portion.
  • the blank mold assembly portion was removed from the lower mold assembly portion, and the half-coated core was ejected from the lower mold cavity.
  • the “weight gain” due to the first shell portion i.e. the difference in weight between the half-coated core and the uncoated core was recorded.
  • the upper mold assembly portion was cycled to a hot stage at 85° C. for 30 seconds.
  • the second shell portion material was added to the upper mold cavity.
  • the half-coated core was then inserted into the upper mold cavity such that the uncoated portion of the core rested within the upper mold cavity.
  • the lower mold assembly portion which had been maintained at 5° C., was then mated with the upper mold assembly portion.
  • the upper mold assembly portion was then cycled to a cold stage at 5° C. for 60 seconds to harden the second shell portion.
  • the lower mold assembly portion was then removed and the finished dosage form, a molded core coated with two different shell portions, was ejected from the upper mold cavity.
  • the weight gain due to the second shell portion i.e. the difference in weight between the finished dosage form, and the half-coated core
  • Curve (d) shows the dissolution profile of pseudoephedrine HCl contained in the first shell portion of the dosage form of this example.
  • Curve (e) depicts the dissolution profile of pseudoephedrine HCl from commercially available immediate release tablets (Sudafed®).
  • Curve (f) depicts the dissolution profile of dextromethorphan HBr from commercially available immediate release coated tablets (Tylenol® Cold caplets).
  • the mobile phase was prepared using 55% acetonitrile and 45% 18 mM Potassium phosphate buffer.
  • the injection volume was 50 ⁇ L with a run time of approximately 8 minutes an a pump flow of 2.0 mL/min.
  • a Zorbax® 300-SCX (4.6 m ⁇ 25 cm) column was used.
  • the curves depicted in FIG. 3 demonstrate that the verapamil HCl was released from the dosage form of the present example in a sustained manner.
  • the dextromethorphan HBr was released from the dosage form of the present example in a delayed manner.
  • the pseudoephedrine HCl was immediately released from the dosage form of the present example.
  • Dosage forms according to the invention comprising a core having a first core portion and a second core portion within a shell having a first shell portion and a second shell portion were prepared as follows.
  • the pseudoephedrine HCl crystal, hydroxypropyl methylcellulose, and PEO (MW 300,000), were first mixed in a plastic bag for 1-2 minutes. This powder mixture was added into the (5 qt) bowl of a planetary mixer (Hobart Corp., Dayton, Ohio). The alcohol was added to the powder mixture while mixing at low speed. The ingredients were mixed for 10 minutes. The resulting granulation was removed from the bowl and dried at room temperature for 12 to 16 hours to remove all residual solvent. The granulation was screened through a #20 mesh screen and were put into a plastic bag. Magnesium stearate was added to the dry granules, followed by mixing for 3 minutes to form the first core portion.
  • This powder mixture was added into the (5 qt) bowl of a planetary mixer (Hobart Corp., Dayton, Ohio). The alcohol was added to the powder mixture while mixing at low speed. The ingredients were mixed for 10 minutes. The resulting granulation was removed from the bowl and dried at room temperature for 12 to 16 hours to remove all residual solvent. The granulation was screened through a #20 mesh screen and were put into a plastic bag. Magnesium stearate was added to the dry granules, followed by mixing for 3 minutes to form the second core portion.
  • Cores were made from equal portions (by weight) of the first and second core portions as follows.
  • a model M hydraulic Carver Laboratory Press (Fred S. Carver, Inc., Hydraulic Equipment, Summit, N.J.) was employed.
  • a round, concave punch and die unit having 0.4455′′ diameter was used for compression.
  • the pseudoephedrine granulation for the first core portion was fed into the cavity mold of the press and was gently tapped. Then the dextromethorphan granulation for the second core portion was fed into the cavity overlying the pseudoephedrine granulation.
  • the granulations were pressed into a solid two-portion core using 1500 lb/sq. in. of compression force.
  • the first shell portion was made using the following ingredients: Mg/Dosage Ingredient Trade Name Manufacturer Weight % Form Cellulose Acetate 398-10 Eastman Chemical 60.0 12.9 Company, Kingsport, TN Polyethylene Oxide Polyox ® WSR N-80 Union Carbide 20.0 4.3 (MW 200,000) Corporation, Danbury, CT Hydroxypropyl Methocel E5 Dow Chemical Company, 20.0 4.3 Methylcellulose Midland, MI Acetone (dried as solvent)
  • the cellulose acetate was added to a beaker containing acetone and mixed using a mixer until all powder was dissolved. An agitating speed of 500 rpm was used. Hydroxypropyl methylcellulose and PEO, which were screened through a #40 mesh screen, were added to the cellulose acetate solution, which was again mixed until all powder was dispersed.
  • the first shell portion material was provided in flowable form.
  • the second shell portion was made using the following ingredients: Mg/Dosaage Ingredient Trade Name Manufacturer Weight % Form Cellulose Acetate 398-10 Eastman Chemical 56.0 12.0 Company, Kingsport, TN Ammonio Methacrylate Eudragit ® RS 100 Roehm America 24.0 5.2 Copolymer Type B Inc., Somerset, NJ Polyethylene Oxide Polyox ® WSR N-80 Union Carbide 20.0 4.3 (MW 200,000) Corporation, Danbury, CT Acetone (dried as solvent)
  • the cellulose acetate was added into a beaker containing acetone and was mixed using a mixer until all powder was dissolved. An agitating speed of 500 rpm was used. Ammonio methacrylate copolymer and PEO, which were screened through a #40 mesh screen, were added to the cellulose acetate solution, which was then mixed until all powder was dispersed. The second shell portion was provided in flowable form.
  • a thermal cycle molding module as described in Example 1 was used to apply the first and second shell portions onto the core.
  • the lower mold assembly portion was first cycled to a cold stage at 25° C. for 30 seconds.
  • the first shell portion material was added to the lower mold cavity.
  • a two-portion core as described above was inserted into the lower mold cavity such that the first core portion, containing pseudoephedrine HCl sustained release granules, was inserted into the lower mold cavity.
  • a blank upper mold assembly portion was mated the lower mold assembly portion.
  • the mold assembly was then cycled to a hot stage at 85° C. for 2 minutes. Next, the assembly was cycled to a cold stage at 5° C. for 1 minute to harden the first shell portion.
  • the blank upper mold assembly portion was then removed from the lower mold assembly portion.
  • the upper mold assembly portion was next cycled to a cold stage at 25° C. for 30 seconds.
  • the second shell portion material was added to the upper mold cavity.
  • the half-coated core, with the first shell portion was inserted into the upper mold cavity such that the uncoated core portion containing dextromethorphan HBr sustained release granules rested within the upper mold cavity.
  • the lower mold assembly portion which had been maintained at 5° C., was then mated with the upper mold assembly portion.
  • the upper mold assembly portion was then cycled to a hot stage at 85° C. for 2 minutes, followed by a cold stage at 5° C. for 1 minute to harden the second shell portion.
  • the lower mold assembly portion was removed and the finished dosage form, a two-portion core coated with two different shell portions, was ejected form the upper mold cavity.
  • the weight gain due to the first and second shell portions i.e. the difference in weights of the finished dosage form and the uncoated core, was recorded.
  • the finished dosage form was dried at room temperature for 24 hours to remove all residual solvent.
  • the mobile phase was prepared using 55% acetonitrile and 45% 18 mM Potassium phosphate buffer.
  • the injection volume was 50 ⁇ L with a run time of approximately 8 minutes an a pump flow of 2.0 mL/min.
  • a Zorbax® 300-SCX (4.6 m ⁇ 25 cm) column was used.
  • Dosage forms of the invention are made in a continuous process using an apparatus comprising two thermal cycle molding modules linked in series via a transfer device as described at pages 14-16 of copending U.S. application Ser. No. 09/966,939, the disclosure of which is incorporated herein by reference.
  • the dosage forms comprise a core coated with a shell comprising a first portion and a second portion.
  • the core is made of a core flowable material comprising the following ingredients: Mg/dosage Ingredient Trade Name Manufacturer Weight % Form Verapamil HCL Extended Verelan PM 300 mg Schwarz Pharma, Inc., 22.0 131 Release Pellets capsules Gainesville, GA Polyethylene Glycol 3350 Carbowax ® Union Carbide 47.0 279 Corporation, Danbury, CT Shellac Powder Mantrose-Haeuser 10.0 59 Company, Atteboro, MA Croscarmellose Sodium Ac-Di-Sol ® FMC Corporation, 21.0 125 Newark, DE
  • PEG is heated to 70° C. and mixed until melted.
  • the shellac powder is screened through a #40 mesh screen, and then added to the molten PEG.
  • the combined ingredients are mixed until all the powder is dispersed.
  • Croscarmellose sodium is added next and the ingredients are mixed for an additional two minutes.
  • the verapamil HCL pellets are then added, and the ingredients are mixed for five more minutes.
  • the first shell portion is made of a first shell portion flowable material comprising the following ingredients: Mg/Dosage Ingredient Trade Name Manufacturer Weight % Form Pseudoephedrine HCl Crystal BASF 30.0 53 PharmaChemikalien GmbH & Co. Ludwigshafen/Rhein. Polyethylene Glycol 3350 Carbowax ® Union Carbide 50.0 89 Corporation, Danbury, CT Polyethylene Oxide Polyox ® WSR N-80 Union Carbide 15.0 27 (MW 200,000) Corporation, Danbury, CT Triethyl Citrate Morflex, Inc., 5.0 9 Greensboro, NC
  • the PEG is heated to 70° C. and mixed until melted.
  • the triethyl citrate is then added to the molten PEG and the mixture is mixed for one minute.
  • the PEO is added thereto, and the ingredients are mixed for 10 additional minutes.
  • the pseudoephedrine hydrochloride is added, and the ingredients are mixed for two more minutes.
  • the second shell portion is made of a second shell portion flowable material comprising the following ingredients: Mg/Dosage Ingredient Trade Name Manufacturer Weight % Form Dextromethorphan HBr Roche Chemical 10.0 16 Co., Belvidere, NJ Polyethylene Glycol 3350 Carbowax ® Union Carbide 50.0 77 Corporation, Danbury, CT Polyethylene Oxide Polyox ® WSR N-80 Union Carbide 15.0 23 (MW 200,000) Corporation, Danbury, CT Shellac Powder Mantrose-Haeuser 10.0 16 Company, Atteboro, MA Croscarmellose Sodium Ac-Di-Sol ® FMC Corporation, 5.0 8 Newark, DE Triethyl Citrate Morflex, Inc., 10.0 16 Greensboro, NC
  • the PEG is heated to 70° C. and mixed until melted.
  • the shellac powder is screened through a #40 mesh screen, and then added to the molten PEG.
  • the combined ingredients are mixed until all powder is dispersed.
  • the triethyl citrate is added next and the ingredients are mixed for one minute.
  • PEO is added to the mixture and the ingredients are again mixed for 10 minutes.
  • Croscarmellose sodium is then added followed by mixing for two additional minutes.
  • dextromethorphan HBr is added and the ingredients are mixed for two more minutes.
  • the thermal cycle molding modules have the general configuration shown in FIG. 3 and pages 27-51 of copending U.S. application Ser. No. 09/966,497, which depicts a thermal cycle molding module 200 comprising a rotor 202 around which a plurality of mold units 204 are disposed.
  • the thermal cycle molding modules include reservoirs 206 (see FIG. 4) for holding the core flowable material, the first shell portion flowable material, and the second shell portion flowable material.
  • each thermal cycle molding module is provided with a temperature control system for rapidly heating and cooling the mold units.
  • FIGS. 55 and 56 of pending U.S. application Ser. No. 09/966,497 depict the temperature control system 600.
  • the cores are made in a first thermal cycle molding module, which is linked via a transfer device to a second thermal cycle molding module.
  • the first thermal cycle molding module has the specific configuration shown in FIG. 26A of copending U.S. application Ser. No. 09/966,497.
  • the first thermal cycle molding module comprises center mold assemblies 212 and upper mold assemblies 214 as shown in FIG. 26C of copending U.S. application Ser. No. 09/966,497, which mate to form mold cavities having a tablet shape.
  • Core flowable material which is heated to a flowable state in reservoir 206, is injected into the resulting mold cavities.
  • the temperature of the core flowable material is then decreased, hardening the core flowable material into tablet-shaped cores.
  • the mold assemblies open and eject the cores, which are received by the first transfer device.
  • the transfer device has the structure shown as 300 in FIG. 3 and described on pages 51-57 of copending U.S. application Ser. No. 09/966,414, the disclosure of which is incorporated by reference. It comprises a plurality of transfer units 304 attached in cantilever fashion to a belt 312 as shown in FIGS. 68 and 69. The transfer device rotates and operates in sync with the thermal cycle molding modules to which it is coupled. Transfer units 304 comprise retainers 330 for holding the cores as they travel around the transfer device.
  • the transfer device transfers the cores to the second thermal cycle molding module, which applies the shell to the cores.
  • the second thermal cycle molding module is of the type shown in FIG. 28A of copending U.S. application Ser. No. 09/966,497.
  • the mold units 204 of the second thermal cycle molding module comprise upper mold assemblies 214, rotatable center mold assemblies 212 and lower mold assemblies 210 as shown in FIG. 28C. Cores are continuously transferred to the mold assemblies, which then close over the cores.
  • first shell portion flowable material heated to a flowable state in reservoir 206
  • second shell portion flowable material heated to a flowable state in reservoir 206
  • the temperature of the second shell portion flowable material is then decreased, hardening it over the other half of the core.
  • the mold assemblies separate, and the finished dosage forms are ejected from the apparatus.
US10/432,488 2001-09-28 2002-09-28 Modified release dosage forms Abandoned US20040062804A1 (en)

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US09966450 2001-09-28
US09/966,450 US6982094B2 (en) 2001-09-28 2001-09-28 Systems, methods and apparatuses for manufacturing dosage forms
US09966509 2001-09-28
US09967414 2001-09-28
US09966497 2001-09-28
US09/967,414 US6742646B2 (en) 2001-09-28 2001-09-28 Systems, methods and apparatuses for manufacturing dosage forms
US09/966,939 US6837696B2 (en) 2001-09-28 2001-09-28 Apparatus for manufacturing dosage forms
US09966939 2001-09-28
US09/966,509 US6767200B2 (en) 2001-09-28 2001-09-28 Systems, methods and apparatuses for manufacturing dosage forms
US09/966,497 US7122143B2 (en) 2001-09-28 2001-09-28 Methods for manufacturing dosage forms
US10/432,488 US20040062804A1 (en) 2001-09-28 2002-09-28 Modified release dosage forms
PCT/US2002/031024 WO2003026625A1 (fr) 2001-09-28 2002-09-28 Formes pharmaceutiques a liberation modifiee

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US20040062804A1 true US20040062804A1 (en) 2004-04-01

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US10/484,485 Abandoned US20040241208A1 (en) 2001-09-28 2002-09-28 Fondant-based pharmaceutical composition
US10/476,238 Abandoned US20040241236A1 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/476,514 Abandoned US20040170750A1 (en) 2001-09-28 2002-09-28 Edible composition and dosage form comprising an edible shell
US10/476,529 Abandoned US20050019407A1 (en) 2001-09-28 2002-09-28 Composite dosage forms
US10/477,334 Expired - Fee Related US7968120B2 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/476,530 Expired - Fee Related US8545887B2 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/432,488 Abandoned US20040062804A1 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/476,504 Abandoned US20040213848A1 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/393,871 Expired - Fee Related US7416738B2 (en) 2001-09-28 2003-03-21 Modified release dosage form
US10/393,610 Abandoned US20030219484A1 (en) 2001-09-28 2003-03-21 Immediate release dosage form comprising shell having openings therein
US10/393,765 Abandoned US20040018327A1 (en) 2001-09-28 2003-03-21 Delayed release dosage forms
US10/393,638 Abandoned US20030232082A1 (en) 2001-09-28 2003-03-21 Modified release dosage forms
US10/393,752 Expired - Fee Related US7635490B2 (en) 2001-09-28 2003-03-21 Modified release dosage form
US12/049,628 Abandoned US20080305150A1 (en) 2001-09-28 2008-03-17 Polymer Composition And Dosage Forms Comprising The Same
US12/391,475 Expired - Fee Related US7972624B2 (en) 2001-09-28 2009-02-24 Method of manufacturing modified release dosage forms

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US10/484,485 Abandoned US20040241208A1 (en) 2001-09-28 2002-09-28 Fondant-based pharmaceutical composition
US10/476,238 Abandoned US20040241236A1 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/476,514 Abandoned US20040170750A1 (en) 2001-09-28 2002-09-28 Edible composition and dosage form comprising an edible shell
US10/476,529 Abandoned US20050019407A1 (en) 2001-09-28 2002-09-28 Composite dosage forms
US10/477,334 Expired - Fee Related US7968120B2 (en) 2001-09-28 2002-09-28 Modified release dosage forms
US10/476,530 Expired - Fee Related US8545887B2 (en) 2001-09-28 2002-09-28 Modified release dosage forms

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US10/393,871 Expired - Fee Related US7416738B2 (en) 2001-09-28 2003-03-21 Modified release dosage form
US10/393,610 Abandoned US20030219484A1 (en) 2001-09-28 2003-03-21 Immediate release dosage form comprising shell having openings therein
US10/393,765 Abandoned US20040018327A1 (en) 2001-09-28 2003-03-21 Delayed release dosage forms
US10/393,638 Abandoned US20030232082A1 (en) 2001-09-28 2003-03-21 Modified release dosage forms
US10/393,752 Expired - Fee Related US7635490B2 (en) 2001-09-28 2003-03-21 Modified release dosage form
US12/049,628 Abandoned US20080305150A1 (en) 2001-09-28 2008-03-17 Polymer Composition And Dosage Forms Comprising The Same
US12/391,475 Expired - Fee Related US7972624B2 (en) 2001-09-28 2009-02-24 Method of manufacturing modified release dosage forms

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050152970A1 (en) * 2004-01-13 2005-07-14 Rinker Roger A. Rapidly disintegrating gelatinous coated tablets
US20060093560A1 (en) * 2004-10-29 2006-05-04 Jen-Chi Chen Immediate release film coating
WO2006049564A1 (fr) * 2004-11-04 2006-05-11 Astrazeneca Ab Nouvelles formulations de pastilles a liberation modifiee pour inhibiteur de la pompe a protons
WO2006049565A1 (fr) * 2004-11-04 2006-05-11 Astrazeneca Ab Nouvelles formulations de comprimes a liberation modifiee pour inhibiteur de la pompe a protons
WO2007109713A2 (fr) * 2006-03-22 2007-09-27 Mcneil- Ppc, Inc. Formes posologiques ayant un revetement aleatoire
US20070274927A1 (en) * 2006-05-23 2007-11-29 Jeffrey T. Haley Adherent polyol troche
US20070293587A1 (en) * 2006-05-23 2007-12-20 Haley Jeffrey T Combating sinus, throat, and blood infections with xylitol delivered in the mouth
US20080300322A1 (en) * 2007-06-01 2008-12-04 Atlantic Pharmaceuticals, Inc. Delivery vehicles containing rosin resins
US20090081278A1 (en) * 2007-09-21 2009-03-26 N.V. Organon Drug Delivery System
US20100158974A1 (en) * 2006-10-19 2010-06-24 Schoemig Albert Coated implant
US20110230831A1 (en) * 2010-03-18 2011-09-22 Alexander Borck Balloon catheter having coating
US8067029B2 (en) 2004-01-13 2011-11-29 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
WO2011107750A3 (fr) * 2010-03-05 2012-05-03 University Of Strathclyde Administration retardée prolongée de médicament
US9474719B2 (en) 2010-03-05 2016-10-25 University Of Strathclyde Pulsatile drug release
US10137091B2 (en) 2010-03-05 2018-11-27 University Of Strathclyde Immediate/delayed drug delivery
US10413504B2 (en) 2013-12-11 2019-09-17 Merck Sharp & Dohme Corp. Intravaginal ring drug delivery system
US10596103B2 (en) 2013-12-11 2020-03-24 Merek Sharp & Dohme B.V. Drug delivery system for delivery of anti-virals
US11229577B2 (en) * 2016-09-09 2022-01-25 Merck Patent Gmbh Process for the manufacture of a solid pharmaceutical administration form

Families Citing this family (296)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8071128B2 (en) 1996-06-14 2011-12-06 Kyowa Hakko Kirin Co., Ltd. Intrabuccally rapidly disintegrating tablet and a production method of the tablets
US6607751B1 (en) * 1997-10-10 2003-08-19 Intellipharamaceutics Corp. Controlled release delivery device for pharmaceutical agents incorporating microbial polysaccharide gum
AU3024399A (en) * 1998-04-03 1999-10-25 Bm Research A/S Controlled release composition
US20090149479A1 (en) * 1998-11-02 2009-06-11 Elan Pharma International Limited Dosing regimen
DE10026698A1 (de) 2000-05-30 2001-12-06 Basf Ag Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung
WO2003024429A1 (fr) 2001-09-21 2003-03-27 Egalet A/S Systeme de liberation a base de polymere
EP1429744A1 (fr) 2001-09-21 2004-06-23 Egalet A/S Systeme a liberation de polymere de morphine
JP2005529059A (ja) 2001-09-28 2005-09-29 マクニール−ピーピーシー・インコーポレイテッド 改質した放出用の投薬形態
US9358214B2 (en) 2001-10-04 2016-06-07 Adare Pharmaceuticals, Inc. Timed, sustained release systems for propranolol
GB0203296D0 (en) 2002-02-12 2002-03-27 Glaxo Group Ltd Novel composition
US8323692B2 (en) 2002-02-21 2012-12-04 Valeant International Bermuda Controlled release dosage forms
JP5069395B2 (ja) * 2002-02-21 2012-11-07 ヴァレアント インターナショナル （バルバドス） エスアールエル トラマドールの少なくとも１つの形の放出が改良された医薬組成物
US7169450B2 (en) 2002-05-15 2007-01-30 Mcneil-Ppc, Inc. Enrobed core
US20060083791A1 (en) 2002-05-24 2006-04-20 Moerck Rudi E Rare earth metal compounds methods of making, and methods of using the same
US20040161474A1 (en) * 2002-05-24 2004-08-19 Moerck Rudi E. Rare earth metal compounds methods of making, and methods of using the same
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
US8637512B2 (en) 2002-07-29 2014-01-28 Glaxo Group Limited Formulations and method of treatment
EP1581197A1 (fr) * 2002-12-11 2005-10-05 Ranbaxy Laboratories, Limited Composition pour enrobage de masquage de gout et procedes d'application de ladite composition
GB0229258D0 (en) * 2002-12-16 2003-01-22 Boots Healthcare Int Ltd Medicinal compositions
US8367111B2 (en) 2002-12-31 2013-02-05 Aptalis Pharmatech, Inc. Extended release dosage forms of propranolol hydrochloride
US20050220870A1 (en) * 2003-02-20 2005-10-06 Bonnie Hepburn Novel formulation, omeprazole antacid complex-immediate release for rapid and sustained suppression of gastric acid
ATE495732T1 (de) 2003-03-26 2011-02-15 Egalet As Morphin-system mit kontrollierter freisetzung
EP1974726B1 (fr) * 2003-03-26 2010-01-13 Egalet A/S Compositions matricielles pour administration contrôlée de substances médicamenteuses
WO2004093850A1 (fr) * 2003-04-24 2004-11-04 Jagotec Ag Comprime a noyau colore
EP1631251B1 (fr) 2003-04-24 2011-06-15 Jagotec AG Comprime a action retardee et a geometrie de noyau definie
EP1633328A4 (fr) * 2003-05-29 2008-07-09 Glykon Technologies Group Llc Procede et composition d'administration stable et controlee d'acide (-)-hydroxycitrique
EP2112920B1 (fr) 2003-06-26 2018-07-25 Intellipharmaceutics Corp. Capsules contenant un inhibiteur de la pompe a protons comprenant des unites secondaires differemment structurees permettant une liberation retardee de l'ingredient actif
US8993599B2 (en) 2003-07-18 2015-03-31 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
ES2654062T3 (es) * 2003-07-24 2018-02-12 Glaxosmithkline Llc Películas de disolución oral
DE102004032051A1 (de) 2004-07-01 2006-01-19 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen Darreichungsform
US8075872B2 (en) 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
DE10361596A1 (de) 2003-12-24 2005-09-29 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102005005446A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Bruchfeste Darreichungsformen mit retardierter Freisetzung
US20070048228A1 (en) 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE10336400A1 (de) 2003-08-06 2005-03-24 Grünenthal GmbH Gegen Missbrauch gesicherte Darreichungsform
CA2535398C (fr) 2003-08-12 2013-11-12 Advancis Pharmaceuticals Corporation Antibiotique, utilisation et formulation associees
US8377952B2 (en) 2003-08-28 2013-02-19 Abbott Laboratories Solid pharmaceutical dosage formulation
US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
JP2005075826A (ja) * 2003-08-29 2005-03-24 Boehringer Ingelheim Internatl Gmbh 多孔質シリカ担体を含有する徐放性製剤
GB0320854D0 (en) 2003-09-05 2003-10-08 Arrow No 7 Ltd Buccal drug delivery
US8627828B2 (en) 2003-11-07 2014-01-14 U.S. Smokeless Tobacco Company Llc Tobacco compositions
EP1691631A4 (fr) 2003-11-07 2012-09-05 Us Smokeless Tobacco Co Compositions a base de tabac
US20050196446A1 (en) * 2004-03-05 2005-09-08 Huang Hai Y. Polymeric compositions and dosage forms comprising the same
US20050196448A1 (en) * 2004-03-05 2005-09-08 Hai Yong Huang Polymeric compositions and dosage forms comprising the same
US20050196442A1 (en) * 2004-03-05 2005-09-08 Huang Hai Y. Polymeric compositions and dosage forms comprising the same
US20050196447A1 (en) * 2004-03-05 2005-09-08 Huang Hai Y. Polymeric compositions and dosage forms comprising the same
WO2005087230A1 (fr) * 2004-03-10 2005-09-22 Taisho Pharmaceutical Co., Ltd. Préparation pharmaceutique solide contenant un médicament hydrosoluble
US8545881B2 (en) 2004-04-19 2013-10-01 Eurand Pharmaceuticals, Ltd. Orally disintegrating tablets and methods of manufacture
EP1758557B1 (fr) 2004-05-11 2011-07-13 Egalet Ltd. Forme galenique gonflant comprenant de la gomme gellane
US7622137B2 (en) * 2004-05-21 2009-11-24 Accu-Break Technologies, Inc. Dosage forms contained within a capsule or sachet
US8906940B2 (en) 2004-05-25 2014-12-09 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US8815916B2 (en) 2004-05-25 2014-08-26 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US20060002986A1 (en) * 2004-06-09 2006-01-05 Smithkline Beecham Corporation Pharmaceutical product
TWI356036B (en) * 2004-06-09 2012-01-11 Smithkline Beecham Corp Apparatus and method for pharmaceutical production
US20050281876A1 (en) * 2004-06-18 2005-12-22 Shun-Por Li Solid dosage form for acid-labile active ingredient
DE102004032049A1 (de) 2004-07-01 2006-01-19 Grünenthal GmbH Gegen Missbrauch gesicherte, orale Darreichungsform
US8394409B2 (en) 2004-07-01 2013-03-12 Intellipharmaceutics Corp. Controlled extended drug release technology
US8609198B2 (en) * 2004-07-21 2013-12-17 Hewlett-Packard Development Company, L.P. Pharmaceutical dose form with a patterned coating and method of making the same
EA200700158A1 (ru) * 2004-07-26 2007-08-31 Тева Фармасьютикал Индастриес Лтд. Лекарственные формы с ядром таблетки, покрытым энтеросолюбильной оболочкой
US7621734B2 (en) * 2004-07-28 2009-11-24 Mars, Incorporated Apparatus and process for preparing confectionery having an inclusion therein using forming rolls and a forming pin
US20060024361A1 (en) * 2004-07-28 2006-02-02 Isa Odidi Disintegrant assisted controlled release technology
US20060024368A1 (en) * 2004-07-30 2006-02-02 Reza Fassihi Compressed composite delivery system for release-rate modulation of bioactives
EP1639899A1 (fr) * 2004-08-23 2006-03-29 Friesland Brands B.V. Composition moussante, soluble/dispersable dans l'eau froide sous forme de poudre
US10624858B2 (en) * 2004-08-23 2020-04-21 Intellipharmaceutics Corp Controlled release composition using transition coating, and method of preparing same
EP1944005A3 (fr) * 2004-09-24 2008-07-23 BioProgress Technology Limited Améliorations supplémentaires dans le compactage et l'enrobage de poudre
EP1807040A1 (fr) * 2004-09-24 2007-07-18 BioProgress Technology Limited Nouvelles améliorations dans le compactage et l'enrobage de poudres
EP2335921A1 (fr) * 2004-09-30 2011-06-22 MonoSolRX, LLC Films multicouches
US9884014B2 (en) 2004-10-12 2018-02-06 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions
EP1809305A4 (fr) * 2004-10-15 2009-12-30 Altairnano Inc Liant phosphate a prise de comprimes reduite
NZ589750A (en) 2004-10-21 2012-07-27 Aptalis Pharmatech Inc Taste-masked pharmaceutical compositions with gastrosoluble pore-formers
US20070281022A1 (en) * 2004-10-27 2007-12-06 Bunick Frank J Dosage forms having a microreliefed surface and methods and apparatus for their production
US8383159B2 (en) 2004-10-27 2013-02-26 Mcneil-Ppc, Inc. Dosage forms having a microreliefed surface and methods and apparatus for their production
US20060088586A1 (en) * 2004-10-27 2006-04-27 Bunick Frank J Dosage forms having a microreliefed surface and methods and apparatus for their production
US20060088587A1 (en) * 2004-10-27 2006-04-27 Bunick Frank J Dosage forms having a microreliefed surface and methods and apparatus for their production
US20060088593A1 (en) * 2004-10-27 2006-04-27 Bunick Frank J Dosage forms having a microreliefed surface and methods and apparatus for their production
US20060087051A1 (en) * 2004-10-27 2006-04-27 Bunick Frank J Dosage forms having a microreliefed surface and methods and apparatus for their production
US20070190133A1 (en) * 2004-10-27 2007-08-16 Bunick Frank J Dosage forms having a microreliefed surface and methods and apparatus for their production
GB0423964D0 (en) * 2004-10-28 2004-12-01 Jagotec Ag Dosage form
DK1836665T3 (da) 2004-11-19 2013-04-15 Glaxosmithkline Llc Fremgangsmåde til specialtilpasset afgivelse af medikamentkombinationsprodukter med variabel dosis til individualisering af terapier
US7404708B2 (en) * 2004-12-07 2008-07-29 Mcneil-Ppc, Inc. System and process for providing at least one opening in dosage forms
US7530804B2 (en) * 2004-12-07 2009-05-12 Mcneil-Ppc, Inc. System and process for providing at least one opening in dosage forms
US20070129402A1 (en) * 2004-12-27 2007-06-07 Eisai Research Institute Sustained release formulations
RU2401125C2 (ru) 2004-12-27 2010-10-10 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Способ стабилизации лекарственного средства против деменции
JP5227591B2 (ja) * 2005-01-07 2013-07-03 サンド・アクチエンゲゼルシヤフト アモキシシリンを含む粒剤の調製方法
DE102005005449A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
EP1858483A4 (fr) * 2005-03-16 2009-07-15 Reddys Lab Ltd Dr Systeme d'administration pour de multiples medicaments
MX2007012220A (es) * 2005-04-06 2007-12-06 Mallinckrodt Inc Formulacion farmaceutica de liberacion por pulsos a base de matriz.
AU2006235483B2 (en) * 2005-04-12 2010-11-25 Elan Pharma International Limited Controlled release compositions comprising a cephalosporin for the treatment of a bacterial infection
US20060233882A1 (en) * 2005-04-15 2006-10-19 Sowden Harry S Osmotic dosage form
US8673352B2 (en) 2005-04-15 2014-03-18 Mcneil-Ppc, Inc. Modified release dosage form
BRPI0608780A2 (pt) * 2005-04-28 2010-11-09 Eisai R&D Man Co Ltd composição contendo fármaco anti-demência
US8802183B2 (en) 2005-04-28 2014-08-12 Proteus Digital Health, Inc. Communication system with enhanced partial power source and method of manufacturing same
EP2392258B1 (fr) 2005-04-28 2014-10-08 Proteus Digital Health, Inc. Systeme pharma-informatique
US9161918B2 (en) 2005-05-02 2015-10-20 Adare Pharmaceuticals, Inc. Timed, pulsatile release systems
DE602006020133D1 (de) * 2005-05-18 2011-03-31 Goemar Lab Sa Laminarin-enthaltende lebensmittel
JP5161075B2 (ja) * 2005-06-03 2013-03-13 エガレット エイ／エス 分散媒体の第１フラクションとマトリックスの第２フラクションを有し、第２フラクションが胃腸の液体に少なくとも部分的に最初に曝される固形の医薬組成物
JP5095615B2 (ja) * 2005-06-27 2012-12-12 バリアント・インターナショナル・（バルバドス）・ソサイアティーズ・ウィズ・リストリクティッド・ライアビリティ ブプロピオン塩の放出調整製剤
US20070009573A1 (en) * 2005-07-07 2007-01-11 L N K International Method of forming immediate release dosage form
US20070015834A1 (en) * 2005-07-18 2007-01-18 Moshe Flashner-Barak Formulations of fenofibrate containing PEG/Poloxamer
DE102005034043B4 (de) * 2005-07-18 2019-12-12 Südzucker Aktiengesellschaft Mannheim/Ochsenfurt Gemisch, enthaltend L-Carnitin und Trehalulose, sowie Produkt enthaltend das Gemisch
US20080058250A1 (en) * 2005-08-17 2008-03-06 Allison Wren Treatment of chronic renal failure and other conditions in domestic animals: compositions and methods
TWI274889B (en) * 2005-10-06 2007-03-01 Elan Microelectronics Corp Resistive touch screen measurement system
KR20080075113A (ko) * 2005-10-14 2008-08-14 하. 룬트벡 아크티에 셀스카브 에스시탈로프람 및 부프로피온을 함유하는 안정한 약학적제형
US8778924B2 (en) 2006-12-04 2014-07-15 Shionogi Inc. Modified release amoxicillin products
US8357394B2 (en) 2005-12-08 2013-01-22 Shionogi Inc. Compositions and methods for improved efficacy of penicillin-type antibiotics
US10064828B1 (en) 2005-12-23 2018-09-04 Intellipharmaceutics Corp. Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems
WO2007086846A1 (fr) * 2006-01-24 2007-08-02 Santarus, Inc. Formules pharmaceutiques utiles pour inhiber la secretion d’acide et procedes de fabrication et d’utilisation correspondants
JP2007224012A (ja) * 2006-01-30 2007-09-06 Fujifilm Corp 酵素架橋したタンパク質ナノ粒子
US20070184111A1 (en) * 2006-02-03 2007-08-09 Pharmavite Llc Hybrid tablet
US20070190131A1 (en) * 2006-02-10 2007-08-16 Perry Ronald L Press-fit rapid release medicament and method and apparatus of manufacturing
AU2007230191A1 (en) * 2006-03-28 2007-10-04 Mcneil-Ppc, Inc. Non-homogenous dosage form coatings
CA2648280C (fr) 2006-04-03 2014-03-11 Isa Odidi Dispositif d'administration a liberation commandee comprenant un enrobage organosol
JP5349290B2 (ja) * 2006-04-03 2013-11-20 オディディ，イサ 薬物送達組成物およびそれを含む医薬品、ならびにその製造方法
US10960077B2 (en) * 2006-05-12 2021-03-30 Intellipharmaceutics Corp. Abuse and alcohol resistant drug composition
CA2657437A1 (fr) * 2006-06-19 2007-12-27 Accu-Break Technologies, Inc. Formes pharmaceutiques secables
UA96457C2 (ru) 2006-08-03 2011-11-10 Нитек Фарма Аг Лечение ревматоидного артрита глюкокортикоидами с отсроченным высвобождением
SA07280459B1 (ar) 2006-08-25 2011-07-20 بيورديو فارما إل. بي. أشكال جرعة صيدلانية للتناول عن طريق الفم مقاومة للعبث تشتمل على مسكن شبه أفيوني
US8399230B2 (en) * 2006-10-12 2013-03-19 Kemin Industries, Inc. Heat-stable enzyme compositions
CN101563074B (zh) 2006-10-20 2012-11-07 麦克内尔-Ppc股份有限公司 乙酰氨基酚/布洛芬组合
MX2009004439A (es) * 2006-10-25 2009-05-11 Mcneil Ppc Inc Composicion de ibuprofeno.
AU2008207200B2 (en) * 2007-01-16 2011-02-17 Egalet Ltd Use of i) a polyglycol and ii) an active drug substance for the preparation of a pharmaceutical composition for i) mitigating the risk of alcohol induced dose dumping and/or ii) reducing the risk of drug abuse
US7767248B2 (en) 2007-02-02 2010-08-03 Overly Iii Harry J Soft chew confectionary with high fiber and sugar content and method for making same
GB0702974D0 (en) * 2007-02-15 2007-03-28 Jagotec Ag Method and apparatus for producing a tablet
US8895061B2 (en) * 2007-03-02 2014-11-25 Meda Pharmaceuticals Inc. Compositions comprising carisoprodol and methods of use thereof
JP5224790B2 (ja) * 2007-03-02 2013-07-03 株式会社明治 固形食品およびその製造方法
DE102007011485A1 (de) 2007-03-07 2008-09-11 Grünenthal GmbH Darreichungsform mit erschwertem Missbrauch
US20080292692A1 (en) * 2007-05-21 2008-11-27 Shira Pilch Impermeable Capsules
WO2008148798A2 (fr) 2007-06-04 2008-12-11 Egalet A/S Compositions pharmaceutiques à libération contrôlée pour un effet prolongé
MX2009013494A (es) * 2007-06-11 2010-01-18 Procter & Gamble Agente benefico que contiene particulas de suministro.
US20080317678A1 (en) * 2007-06-22 2008-12-25 Szymczak Christopher E Laser Marked Dosage Forms
US20080317677A1 (en) * 2007-06-22 2008-12-25 Szymczak Christopher E Laser Marked Dosage Forms
US20090004248A1 (en) * 2007-06-29 2009-01-01 Frank Bunick Dual portion dosage lozenge form
ES2692437T3 (es) * 2007-08-13 2018-12-03 Abuse Deterrent Pharmaceutical Llc Fármacos resistentes al abuso, método de uso y método de preparación
US20090060983A1 (en) * 2007-08-30 2009-03-05 Bunick Frank J Method And Composition For Making An Orally Disintegrating Dosage Form
EP2197448A4 (fr) * 2007-09-12 2010-11-17 Elan Pharma Int Ltd Schéma posologique
FR2921835B1 (fr) * 2007-10-05 2012-05-04 Soc Dexploitation De Produits Pour Les Industries Chimiques Seppic Composition d'enrobage comprenant du polydextrose, procede pour sa preparation et utilisation pour enrober les formes solides ingerables
US20090105561A1 (en) * 2007-10-17 2009-04-23 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Medical or veterinary digestive tract utilization systems and methods
US8303573B2 (en) 2007-10-17 2012-11-06 The Invention Science Fund I, Llc Medical or veterinary digestive tract utilization systems and methods
US8789536B2 (en) 2007-10-17 2014-07-29 The Invention Science Fund I, Llc Medical or veterinary digestive tract utilization systems and methods
US8707964B2 (en) * 2007-10-31 2014-04-29 The Invention Science Fund I, Llc Medical or veterinary digestive tract utilization systems and methods
DK2180882T3 (da) 2007-10-19 2013-05-27 Otsuka Pharma Co Ltd Farmaceutisk faststofsammensætning af matrix-type
US8808276B2 (en) * 2007-10-23 2014-08-19 The Invention Science Fund I, Llc Adaptive dispensation in a digestive tract
US20090163894A1 (en) * 2007-10-31 2009-06-25 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Medical or veterinary digestive tract utilization systems and methods
US8109920B2 (en) * 2007-10-31 2012-02-07 The Invention Science Fund I, Llc Medical or veterinary digestive tract utilization systems and methods
KR101560176B1 (ko) * 2007-10-31 2015-10-14 맥네일-피피씨, 인코포레이티드 구강내 붕해성 투여 형태
US8333754B2 (en) * 2007-10-31 2012-12-18 The Invention Science Fund I, Llc Medical or veterinary digestive tract utilization systems and methods
US8808271B2 (en) * 2007-10-31 2014-08-19 The Invention Science Fund I, Llc Medical or veterinary digestive tract utilization systems and methods
US20090137866A1 (en) * 2007-11-28 2009-05-28 Searete Llc, A Limited Liability Corporation Of The State Delaware Medical or veterinary digestive tract utilization systems and methods
CA2739668C (fr) 2008-01-04 2016-10-11 Schabar Research Associates Llc Utilisation de composes de potentialisation analgesique pour potentialiser les proprietes analgesiques d'un compose analgesique
KR101616246B1 (ko) 2008-01-25 2016-05-02 그뤼넨탈 게엠베하 약제학적 투여형
WO2009154810A2 (fr) * 2008-02-25 2009-12-23 Dr. Reddy's Laboratories Ltd. Systèmes d'administration de multiples principes actifs
CN102105136B (zh) 2008-03-11 2014-11-26 蒂宝制药公司 包含非-阿片类止痛剂和阿片类止痛剂的组合的胃滞留型缓释剂型
US8372432B2 (en) 2008-03-11 2013-02-12 Depomed, Inc. Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic
MX2010012039A (es) 2008-05-09 2010-11-30 Gruenenthal Gmbh Proceso para la preparacion de una formulacion de polvo intermedia y una forma de dosificacion solida final bajo el uso de un paso de congelacion por rocio.
WO2009137648A1 (fr) * 2008-05-09 2009-11-12 Aptapharma, Inc. Pastilles multicouches inhibant la pompe à protons
US20110165290A1 (en) * 2008-05-14 2011-07-07 Cadbury Adams Usa Llc Confectionery with enzymatically manipulated texture
WO2009146537A1 (fr) * 2008-06-02 2009-12-10 Pharmascience Inc. Système multicouche d'apport de médicament à libération progressive
KR200452140Y1 (ko) * 2008-06-20 2011-02-08 주식회사 부성시스템 비닐하우스의 부직포개폐기용 제어장치
ES2630805T3 (es) 2008-07-14 2017-08-24 Polypid Ltd. Composición de vehículo de fármaco de liberación sostenida
KR200450450Y1 (ko) * 2008-07-16 2010-10-04 이봉석 포지션 리미트 스위치 케이스
JP2011530529A (ja) * 2008-08-07 2011-12-22 アバントール パフォーマンス マテリアルズ， インコーポレイテッド ゴムおよび糖アルコールを含む徐放性組成物
US8038424B2 (en) * 2008-09-22 2011-10-18 Xerox Corporation System and method for manufacturing sold ink sticks with an injection molding process
FR2936952A1 (fr) * 2008-10-09 2010-04-16 Monique Bellec Administration par voie orale de medicaments et complements nutritionnels
IT1394597B1 (it) * 2008-11-05 2012-07-05 Politi Granulazione a secco in flusso di gas.
WO2010067478A1 (fr) * 2008-12-12 2010-06-17 株式会社ミツヤコーポレーション Aliment et son procédé de traitement
EP2391369A1 (fr) * 2009-01-26 2011-12-07 Nitec Pharma AG Traitement de l'asthme par glucocorticoïde à libération retardée
NZ594207A (en) 2009-02-06 2013-03-28 Egalet Ltd Immediate release composition resistant to abuse by intake of alcohol
NZ594208A (en) 2009-02-06 2012-10-26 Egalet Ltd Pharmaceutical compositions resistant to abuse
ES2797493T3 (es) * 2009-02-13 2020-12-02 Romark Laboratories Lc Formulaciones farmacéuticas de liberación controlada de nitazoxanida
MX2011011506A (es) 2009-04-28 2012-05-08 Proteus Biomedical Inc Marcadores de eventos ingeribles altamente confiables y metodos para utilizar los mismos.
CA2760037A1 (fr) * 2009-05-12 2010-11-18 Bpsi Holdings, Llc Enrobages par film contenant des antiadhesifs a fines particules et substrats enrobes associes
US9498440B2 (en) 2009-05-22 2016-11-22 Inventia Healthcare Private Limited Extended release pharmaceutical compositions
NZ597283A (en) 2009-06-24 2013-07-26 Egalet Ltd Controlled release formulations
US8992979B2 (en) 2009-07-14 2015-03-31 Polypid Ltd. Sustained-release drug carrier composition
RU2015138422A (ru) 2009-07-22 2018-12-25 Грюненталь Гмбх Стабильная при окислении, прочная на излом лекарственная форма
MX2012000317A (es) 2009-07-22 2012-02-08 Gruenenthal Gmbh Forma de dosificacion de liberacion controlada extruida por fusion en caliente.
US20120164280A1 (en) * 2009-07-24 2012-06-28 Nihon Kraft Foods Limited Multiple-Region Candy and Manufacturing Method Therefor
WO2011017389A1 (fr) 2009-08-05 2011-02-10 Idenix Pharmaceuticals, Inc. Inhibiteurs macrocycliques de la sérine protéase macrocyclique utiles contre les infections virales, en particulier le virus de l’hépatite c
US20120141584A1 (en) * 2009-08-26 2012-06-07 Aptapharma, Inc. Multilayer Minitablets
RU2012112552A (ru) * 2009-08-31 2013-10-10 Дипомед, Инк. Удерживаемые в желудке фармацевтические композиции для немедленного и продленного высвобождения ацетаминофена
CA2772215C (fr) * 2009-09-01 2017-05-23 Rhodia Operations Compositions de polymere
US20110070286A1 (en) * 2009-09-24 2011-03-24 Andreas Hugerth Process for the manufacture of nicotine-comprising chewing gum and nicotine-comprising chewing gum manufactured according to said process
US8313768B2 (en) * 2009-09-24 2012-11-20 Mcneil-Ppc, Inc. Manufacture of tablet having immediate release region and sustained release region
US20110318411A1 (en) 2010-06-24 2011-12-29 Luber Joseph R Multi-layered orally disintegrating tablet and the manufacture thereof
US8871263B2 (en) * 2009-09-24 2014-10-28 Mcneil-Ppc, Inc. Manufacture of tablet in a die utilizing radiofrequency energy and meltable binder
EP2316432A1 (fr) * 2009-10-30 2011-05-04 ratiopharm GmbH Composition contenant de la fésotérodine et des fibres alimentaires
WO2011056764A1 (fr) 2009-11-05 2011-05-12 Ambit Biosciences Corp. Imidazo[2,1-b][1,3]benzothiazoles enrichis en isotopes ou fluores
CA2782285A1 (fr) 2009-12-02 2011-06-09 Luigi Mapelli Microcapsules de fexofenadine et compositions les contenant
UA109424C2 (uk) * 2009-12-02 2015-08-25 Фармацевтичний продукт, фармацевтична таблетка з електронним маркером і спосіб виготовлення фармацевтичної таблетки
EP2509587A2 (fr) * 2009-12-07 2012-10-17 McNeil-PPC, Inc. Revêtement par immersion partielle de formes pharmaceutiques pour libération modifiée
AR079528A1 (es) 2009-12-18 2012-02-01 Idenix Pharmaceuticals Inc Inhibidores de arileno o heteroarileno 5,5-fusionado del virus de la hepatitis c
WO2011078993A1 (fr) * 2009-12-21 2011-06-30 Aptapharma, Inc. Comprimés multicouches à enrobage fonctionnel
CN102892406B (zh) 2010-01-19 2015-04-08 波利皮得有限公司 缓释核酸基质组合物
WO2011094890A1 (fr) 2010-02-02 2011-08-11 Argusina Inc. Dérivés phénylalanines et leur utilisation comme modulateurs non peptidiques du récepteur de glp-1
WO2011095314A2 (fr) 2010-02-03 2011-08-11 Grünenthal GmbH Préparation d'une composition pharmaceutique pulvérulente au moyen d'une extrudeuse
US9138309B2 (en) 2010-02-05 2015-09-22 Allergan, Inc. Porous materials, methods of making and uses
US9205577B2 (en) * 2010-02-05 2015-12-08 Allergan, Inc. Porogen compositions, methods of making and uses
WO2011110989A1 (fr) * 2010-03-11 2011-09-15 Wockhardt Limited Dispositif pour produire une forme posologique à trou et son procédé de production
WO2011112689A2 (fr) 2010-03-11 2011-09-15 Ambit Biosciences Corp. Sels d'indazolylpyrrolotriazine
US9743688B2 (en) * 2010-03-26 2017-08-29 Philip Morris Usa Inc. Emulsion/colloid mediated flavor encapsulation and delivery with tobacco-derived lipids
KR20170121299A (ko) 2010-04-07 2017-11-01 프로테우스 디지털 헬스, 인코포레이티드 소형의 섭취가능한 장치
US11202853B2 (en) * 2010-05-11 2021-12-21 Allergan, Inc. Porogen compositions, methods of making and uses
EP2568989B1 (fr) 2010-05-12 2021-03-24 Spectrum Pharmaceuticals, Inc. Hydroxyde de carbonate de lanthane, oxycarbonate de lanthane, et procédés pour leur fabrication et méthodes pour leur utilisation
US20110280936A1 (en) * 2010-05-17 2011-11-17 Aptapharma, Inc. Self Breaking Tablets
WO2011161666A2 (fr) * 2010-06-21 2011-12-29 White Innovation Ltd. Inclusion de liquides dans des capsules
WO2012030913A1 (fr) 2010-09-01 2012-03-08 Ambit Biosciences Corporation Pyrazolylaminoquinazoline optiquement active, et ses compositions pharmaceutiques et méthodes d'utilisation
EP2611792B1 (fr) 2010-09-01 2017-02-01 Ambit Biosciences Corporation Sels hydrobromiques d'une pyrazolylaminoquinazoline
CA2808219C (fr) 2010-09-02 2019-05-14 Gruenenthal Gmbh Forme pharmaceutique inviolable comportant un sel inorganique
ES2487244T3 (es) 2010-09-02 2014-08-20 Grünenthal GmbH Forma de dosificación resistente a la manipulación que comprende un polímero aniónico
JP2014504902A (ja) 2010-11-22 2014-02-27 プロテウス デジタル ヘルス， インコーポレイテッド 医薬品を有する摂取可能なデバイス
AU2011338530B2 (en) 2010-12-06 2017-06-15 Follica, Inc. Methods for treating baldness and promoting hair growth
US10821085B2 (en) * 2010-12-07 2020-11-03 Kimberly-Clark Worldwide, Inc. Wipe coated with a botanical composition having antimicrobial properties
US9233076B2 (en) 2010-12-13 2016-01-12 Purdue Pharma L.P. Controlled release dosage forms
WO2012080050A1 (fr) 2010-12-14 2012-06-21 F. Hoffmann-La Roche Ag Formes solides d'un composé de phénoxybenzènesulfonyle
JP2014503597A (ja) 2011-01-31 2014-02-13 セルジーン コーポレイション シチジンアナログの医薬組成物及びその使用方法
US9353100B2 (en) 2011-02-10 2016-05-31 Idenix Pharmaceuticals Llc Macrocyclic serine protease inhibitors, pharmaceutical compositions thereof, and their use for treating HCV infections
US20120252721A1 (en) 2011-03-31 2012-10-04 Idenix Pharmaceuticals, Inc. Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor
KR102059698B1 (ko) * 2011-06-06 2019-12-26 오크 크레스트 인스티튜트 오브 사이언스 심지 방출창을 도입한 약물 전달 장치
USD723766S1 (en) 2011-06-30 2015-03-10 Intercontinental Great Brands Llc Confectionary article
WO2015112603A1 (fr) 2014-01-21 2015-07-30 Proteus Digital Health, Inc. Produit ingérable pouvant être mâché et système de communication associé
US9756874B2 (en) 2011-07-11 2017-09-12 Proteus Digital Health, Inc. Masticable ingestible product and communication system therefor
AU2012292418B2 (en) 2011-07-29 2017-02-16 Grunenthal Gmbh Tamper-resistant tablet providing immediate drug release
CA2839123A1 (fr) 2011-07-29 2013-02-07 Grunenthal Gmbh Comprime anti-manipulation permettant une liberation immediate de medicament
US20130078307A1 (en) 2011-09-22 2013-03-28 Niconovum Usa, Inc. Nicotine-containing pharmaceutical composition
US9474303B2 (en) 2011-09-22 2016-10-25 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US9629392B2 (en) 2011-09-22 2017-04-25 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US9084439B2 (en) 2011-09-22 2015-07-21 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
AU2011378770B2 (en) 2011-10-14 2015-01-29 Hill's Pet Nutrition, Inc. Process for preparing a food composition
KR101384055B1 (ko) * 2012-02-02 2014-04-14 한국원자력연구원 버스트형 지연 방출 제어 조성물 및 이의 제조방법
MX356421B (es) 2012-02-28 2018-05-29 Gruenenthal Gmbh Forma de dosificacion resistente a la manipulacion indebida que comprende un compuesto farmacologicamente activo y un polimero anionico.
US8916555B2 (en) 2012-03-16 2014-12-23 Axikin Pharmaceuticals, Inc. 3,5-diaminopyrazole kinase inhibitors
US20130261372A1 (en) * 2012-03-30 2013-10-03 Elwha LLC, a limited liability company of the State of Delaware Device, System, and Method for Delivery of Sugar Glass Stabilized Compositions
CN104394851B (zh) 2012-04-18 2017-12-01 格吕伦塔尔有限公司 抗篡改和抗剂量‑倾泻药物剂型
US9985320B2 (en) * 2012-04-30 2018-05-29 Carnegie Mellon University Water-activated, ingestible battery
US9445971B2 (en) * 2012-05-01 2016-09-20 Johnson & Johnson Consumer Inc. Method of manufacturing solid dosage form
US9233491B2 (en) 2012-05-01 2016-01-12 Johnson & Johnson Consumer Inc. Machine for production of solid dosage forms
US9511028B2 (en) 2012-05-01 2016-12-06 Johnson & Johnson Consumer Inc. Orally disintegrating tablet
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US9693962B2 (en) 2012-06-05 2017-07-04 Takeda Pharmaceutical Limited Dry-coated tablet
KR20150059167A (ko) 2012-07-06 2015-05-29 에갈렛 리미티드 제어된 방출을 위한 남용 제지 약학적 조성물
CN102824640A (zh) * 2012-08-06 2012-12-19 济南圣泉唐和唐生物科技有限公司 一种胶囊壳及其制备方法
US20140193546A1 (en) * 2013-01-09 2014-07-10 Alexander Vigneri Coated chocolate confection with improved dye acceptance
WO2014120669A1 (fr) 2013-01-29 2014-08-07 Proteus Digital Health, Inc. Films polymères hautement dilatables et compositions les contenant
DE102013004263A1 (de) 2013-03-13 2014-09-18 Martin Lipsdorf Schnell lösliche orale Darreichungsform und Methode zur Herstellung derselben
US10175376B2 (en) 2013-03-15 2019-01-08 Proteus Digital Health, Inc. Metal detector apparatus, system, and method
JP6395800B2 (ja) 2013-03-15 2018-09-26 インキューブ ラブズ， エルエルシー 多段階生分解性薬物送達プラットフォーム
US20140275038A1 (en) 2013-03-15 2014-09-18 Inspirion Delivery Technologies, Llc Abuse deterrent compositions and methods of use
US9470489B2 (en) * 2013-05-14 2016-10-18 Kerry Thaddeus Bowden Airsoft marking round
AR096438A1 (es) 2013-05-29 2015-12-30 Gruenenthal Gmbh Forma de dosificación resistente al uso indebido con perfil de liberación bimodal, proceso
CA2907950A1 (fr) 2013-05-29 2014-12-04 Grunenthal Gmbh Forme pharmaceutique inviolable contenant une ou plusieurs particules
BR112016000194A8 (pt) 2013-07-12 2019-12-31 Gruenenthal Gmbh forma de dosagem resistente à violação contendo o polímero de acetato de etileno-vinila
US9796576B2 (en) 2013-08-30 2017-10-24 Proteus Digital Health, Inc. Container with electronically controlled interlock
NZ631142A (en) 2013-09-18 2016-03-31 Axikin Pharmaceuticals Inc Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors
EP3046924A1 (fr) 2013-09-20 2016-07-27 IDENIX Pharmaceuticals, Inc. Inhibiteurs du virus de l'hépatite c
US10084880B2 (en) 2013-11-04 2018-09-25 Proteus Digital Health, Inc. Social media networking based on physiologic information
CN105934241B (zh) 2013-11-26 2020-06-05 格吕伦塔尔有限公司 通过低温研磨制备粉末状药物组合物
US10300136B2 (en) * 2013-12-16 2019-05-28 Massachusetts Institute Of Technology Micromolded or 3-D printed pulsatile release vaccine formulations
US10137092B2 (en) * 2013-12-23 2018-11-27 Xiaoguang WEN Double-layer tablet and preparation method thereof
WO2015105992A1 (fr) 2014-01-10 2015-07-16 Mcneil-Ppc, Inc. Procédé pour fabriquer un comprimé par radiofréquence et particules revêtues à perte
US9375033B2 (en) 2014-02-14 2016-06-28 R.J. Reynolds Tobacco Company Tobacco-containing gel composition
US20170066779A1 (en) 2014-03-05 2017-03-09 Idenix Pharmaceuticals Llc Solid forms of a flaviviridae virus inhibitor compound and salts thereof
US10005765B2 (en) 2014-03-20 2018-06-26 Capella Therapeutics, Inc. Benzimidazole derivatives as ERBB tyrosine kinase inhibitors for the treatment of cancer
CA2943231C (fr) 2014-03-20 2023-10-24 Capella Therapeutics, Inc. Derives de benzimidazole en tant qu'inhibiteurs de la tyrosine kinase erbb pour le traitement du cancer
WO2015173195A1 (fr) 2014-05-12 2015-11-19 Grünenthal GmbH Formulation pour capsule à libération immédiate résistant aux manipulations illicites comprenant du tapentadol
JP2017516789A (ja) 2014-05-26 2017-06-22 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング エタノール過量放出に対して防護されている多粒子
US10729685B2 (en) 2014-09-15 2020-08-04 Ohemo Life Sciences Inc. Orally administrable compositions and methods of deterring abuse by intranasal administration
HUE049801T2 (hu) 2014-12-23 2020-10-28 Sma Therapeutics Inc 3,5-diaminopirazol kináz inhibitorok
DE202016008309U1 (de) * 2015-01-22 2017-07-14 Pfeifer & Langen GmbH & Co. KG Cellobiosehaltige Zuckermasse
US10174275B2 (en) * 2015-01-30 2019-01-08 Follmann Gmbh & Co. Kg Thermally opening stable core/shell microcapsules
USD765828S1 (en) 2015-02-19 2016-09-06 Crossford International, Llc Chemical tablet
US9839212B2 (en) 2015-04-16 2017-12-12 Bio-Lab, Inc. Multicomponent and multilayer compacted tablets
EP3285745A1 (fr) 2015-04-24 2018-02-28 Grünenthal GmbH Forme galénique inviolable avec libération immédiate et résistance à l'extraction par solvant.
US11051543B2 (en) 2015-07-21 2021-07-06 Otsuka Pharmaceutical Co. Ltd. Alginate on adhesive bilayer laminate film
CA2998259A1 (fr) 2015-09-10 2017-03-16 Grunenthal Gmbh Protection contre un surdosage par voie orale a l'aide de formulations a liberation immediate dissuasives d'abus
CN108712900A (zh) 2015-12-19 2018-10-26 第时间美国泛型药物有限公司 软咀嚼片剂药物制剂
US20190022013A1 (en) 2015-12-19 2019-01-24 First Time Us Generics Llc Soft-chew tablet pharmaceutical formulations
JP2017158534A (ja) * 2016-03-07 2017-09-14 焼津水産化学工業株式会社 チップ状食品の製造方法及びチップ状食品
WO2017159653A1 (fr) * 2016-03-15 2017-09-21 アステラス製薬株式会社 Comprimé
CN109843149B (zh) 2016-07-22 2020-07-07 普罗秋斯数字健康公司 可摄入事件标记的电磁感测和检测
CA3038263C (fr) 2016-09-26 2022-04-05 The Procter & Gamble Company Forme galenique a liberation prolongee
CN109963499B (zh) 2016-10-26 2022-02-25 大冢制药株式会社 用于制造具有可吸收事件标记器的胶囊的方法
CN106945323B (zh) * 2017-03-14 2018-11-02 常熟市双月机械有限公司 一种高效率的金属粉末液压机
US10493026B2 (en) 2017-03-20 2019-12-03 Johnson & Johnson Consumer Inc. Process for making tablet using radiofrequency and lossy coated particles
US10604631B2 (en) * 2017-04-07 2020-03-31 The Procter & Gamble Company Water-soluble films
DE102017107845A1 (de) 2017-04-11 2018-10-11 Gelita Ag Gelatineprodukt mit einer Kernkomponente und Verfahren zu dessen Herstellung
WO2018237212A1 (fr) 2017-06-22 2018-12-27 The Procter & Gamble Company Films comprenant une couche hydrosoluble et un revêtement organique déposé en phase vapeur
WO2018237213A1 (fr) 2017-06-22 2018-12-27 The Procter & Gamble Company Films comprenant une couche hydrosoluble et un revêtement inorganique déposé en phase vapeur
US10537585B2 (en) 2017-12-18 2020-01-21 Dexcel Pharma Technologies Ltd. Compositions comprising dexamethasone
CA3090183C (fr) * 2018-03-05 2021-06-01 Kashiv Biosciences, Llc Compositions pharmaceutiques programmables pour la liberation chrono de medicament
EP3587467A1 (fr) * 2018-06-25 2020-01-01 Rudolf GmbH Particule c ur-écorce fonctionnelle à parois multiples
CN112351687A (zh) * 2018-06-28 2021-02-09 马斯公司 含碳酸钙的改进可食用油墨配制剂
KR102151342B1 (ko) * 2019-03-18 2020-09-02 박문수 구강용 캡슐 및 이의 제조방법
CN110006918B (zh) * 2019-04-17 2021-04-30 湖北三环锻造有限公司 一种用于渗透探伤工艺的渗透探伤剂
US20210275461A1 (en) * 2019-09-12 2021-09-09 Nulixir Inc. Particles for administration of active ingredients and methods of making the same
AU2021310264A1 (en) 2020-07-15 2023-02-09 Schabar Research Associates Llc Unit oral dose compositions composed of ibuprofen and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
CA3124579A1 (fr) 2020-07-15 2022-01-15 Schabar Research Associates Llc Compositions de doses orales unitaires composees de naproxene sodique et de famotidine pour le traitement des douleurs aigues et la reduction de la gravite des aigreurs et/ou du risque d'aigreurs

Citations (96)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US599865A (en) * 1898-03-01 Emanuel l
US2307371A (en) * 1941-08-13 1943-01-05 Ray O Vac Co Molding process
US2996431A (en) * 1953-12-16 1961-08-15 Barry Richard Henry Friable tablet and process for manufacturing same
US3085942A (en) * 1960-12-28 1963-04-16 Hoffmann La Roche Antitussive compositions and preparation
US3146169A (en) * 1960-01-21 1964-08-25 Burroughs Wellcome Co Pharmaceutical formulations and their manufacture
US3760804A (en) * 1971-01-13 1973-09-25 Alza Corp Improved osmotic dispenser employing magnesium sulphate and magnesium chloride
US3832252A (en) * 1970-09-29 1974-08-27 T Higuchi Method of making a drug-delivery device
US4097606A (en) * 1975-10-08 1978-06-27 Bristol-Myers Company APAP Tablet containing an alkali metal carboxymethylated starch and processes for manufacturing same
US4139589A (en) * 1975-02-26 1979-02-13 Monique Beringer Process for the manufacture of a multi-zone tablet and tablet manufactured by this process
US4173626A (en) * 1978-12-11 1979-11-06 Merck & Co., Inc. Sustained release indomethacin
US4230693A (en) * 1975-04-21 1980-10-28 Armour-Dial, Inc. Antacid tablets and processes for their preparation
US4271206A (en) * 1979-10-26 1981-06-02 General Foods Corporation Gasified candy having a predetermined shape
US4371516A (en) * 1976-10-06 1983-02-01 John Wyeth & Brother Limited Articles for carrying chemicals
US4372942A (en) * 1981-08-13 1983-02-08 Beecham Inc. Candy base and liquid center hard candy made therefrom
US4425332A (en) * 1978-09-21 1984-01-10 Beecham Group Limited Antacid composition
US4473526A (en) * 1980-01-23 1984-09-25 Eugen Buhler Method of manufacturing dry-pressed molded articles
US4518335A (en) * 1984-03-14 1985-05-21 Allied Corporation Dilatant mold and dilatant molding apparatus
US4576604A (en) * 1983-03-04 1986-03-18 Alza Corporation Osmotic system with instant drug availability
US4661521A (en) * 1984-04-30 1987-04-28 Mallinckrodt, Inc. Direct tableting acetaminophen compositions
US4666212A (en) * 1984-06-15 1987-05-19 Crucible S.A. Metal value recovery
US4686212A (en) * 1985-08-13 1987-08-11 Pharmacontrol Corp. Stable sodium aspirin tablet compositions
US4749575A (en) * 1983-10-03 1988-06-07 Bio-Dar Ltd. Microencapsulated medicament in sweet matrix
US4757090A (en) * 1986-07-14 1988-07-12 Mallinckrodt, Inc. Direct tableting acetaminophen compositions
US4762719A (en) * 1986-08-07 1988-08-09 Mark Forester Powder filled cough product
US4781714A (en) * 1983-11-02 1988-11-01 Alza Corporation Dispenser for delivering thermo-responsive composition
US4816262A (en) * 1986-08-28 1989-03-28 Universite De Montreal Controlled release tablet
US4820524A (en) * 1987-02-20 1989-04-11 Mcneilab, Inc. Gelatin coated caplets and process for making same
US4851226A (en) * 1987-11-16 1989-07-25 Mcneil Consumer Products Company Chewable medicament tablet containing means for taste masking
US4863742A (en) * 1986-06-20 1989-09-05 Elan Corporation Plc Controlled absorption pharmaceutical composition
US4882167A (en) * 1983-05-31 1989-11-21 Jang Choong Gook Dry direct compression compositions for controlled release dosage forms
US4894236A (en) * 1988-01-12 1990-01-16 Choong-Gook Jang Direct compression tablet binders for acetaminophen
US4906478A (en) * 1988-12-12 1990-03-06 Valentine Enterprises, Inc. Simethicone/calcium silicate composition
US4929446A (en) * 1988-04-19 1990-05-29 American Cyanamid Company Unit dosage form
US4960169A (en) * 1989-06-20 1990-10-02 Modien Manufacturing Co. Baffle for tubular heat exchanger header
US4984240A (en) * 1988-12-22 1991-01-08 Codex Corporation Distributed switching architecture for communication module redundancy
US5002970A (en) * 1981-07-31 1991-03-26 Eby Iii George A Flavor masked ionizable zinc compositions for oral absorption
US5089270A (en) * 1990-05-15 1992-02-18 L. Perrigo Company Capsule-shaped tablet
US5146730A (en) * 1989-09-20 1992-09-15 Banner Gelatin Products Corp. Film-enrobed unitary-core medicament and the like
US5188840A (en) * 1985-09-26 1993-02-23 Chugai Seiyaku Kabushiki Kaisha Slow-release pharmaceutical agent
US5200191A (en) * 1991-09-11 1993-04-06 Banner Gelatin Products Corp. Softgel manufacturing process
US5213738A (en) * 1990-05-15 1993-05-25 L. Perrigo Company Method for making a capsule-shaped tablet
US5213808A (en) * 1989-09-22 1993-05-25 Buhk Meditec A/A Controlled release article with pulsatile release
US5228916A (en) * 1990-11-05 1993-07-20 Mcneil-Ppc, Inc. Apparatus for creating a gelatin coating
US5229164A (en) * 1985-12-19 1993-07-20 Capsoid Pharma Gmbh Process for producing individually dosed administration forms
US5275822A (en) * 1989-10-19 1994-01-04 Valentine Enterprises, Inc. Defoaming composition
US5286497A (en) * 1991-05-20 1994-02-15 Carderm Capital L.P. Diltiazem formulation
US5368863A (en) * 1990-01-24 1994-11-29 Alza Corporation Long-term delivery device with early startup
US5391378A (en) * 1993-02-22 1995-02-21 Elizabeth-Hata International, Inc. Two-part medicinal tablet and method of manufacture
US5393533A (en) * 1988-09-09 1995-02-28 The Ronald T. Dodge Company Pharmaceuticals microencapsulated by vapor deposited polymers and method
US5405642A (en) * 1991-02-27 1995-04-11 Janssen Pharmaceutica N.V. Method of highlighting intagliations in tablets
US5415868A (en) * 1993-06-09 1995-05-16 L. Perrigo Company Caplets with gelatin cover and process for making same
US5427814A (en) * 1988-02-03 1995-06-27 Nestec S.A. Process for protecting a fat against oxidation
US5436026A (en) * 1990-11-05 1995-07-25 Mcneil-Ppc, Inc. Discharge and transfer system for apparatus for gelatin coating tablets
US5456920A (en) * 1993-02-10 1995-10-10 Takeda Chemical Industries, Ltd. Uncoated tablets and method of producing the same
US5464633A (en) * 1994-05-24 1995-11-07 Jagotec Ag Pharmaceutical tablets releasing the active substance after a definite period of time
US5464631A (en) * 1990-06-27 1995-11-07 Warner-Lambert Company Encapsulated dosage forms
US5469983A (en) * 1993-06-19 1995-11-28 Sado Yawata Heat insulating container and container holding member
US5489436A (en) * 1991-06-14 1996-02-06 Mcneil-Ppc, Inc. Taste mask coatings for preparation of chewable pharmaceutical tablets
US5511361A (en) * 1992-08-07 1996-04-30 Warner-Lambert Company Encapsulation method
US5538125A (en) * 1990-11-05 1996-07-23 Mcneil-Ppc, Inc. Indexing and feeding systems for apparatus for gelatin coating tablets
US5558829A (en) * 1994-03-04 1996-09-24 Mentor Corporation Method for providing a prosthesis with an injection port
US5578336A (en) * 1995-06-07 1996-11-26 Monte; Woodrow C. Confection carrier for vitamins, enzymes, phytochemicals and ailmentary vegetable compositions and method of making
US5614207A (en) * 1995-06-30 1997-03-25 Mcneil-Ppc, Inc. Dry mouth lozenge
US5641536A (en) * 1993-08-30 1997-06-24 Warner-Lambert Company Tablet coating method
US5679406A (en) * 1990-11-05 1997-10-21 Mcneil-Ppc, Inc. Tablet dipping systems for apparatus for gelatin coating tablets
US5681584A (en) * 1993-04-23 1997-10-28 Ciba-Geigy Corporation Controlled release drug delivery device
US5711961A (en) * 1994-07-26 1998-01-27 Apr Applied Pharma Research S.A. Pharmaceutical compositions based on chewing gum and a method for the preparation thereof
US5738874A (en) * 1992-09-24 1998-04-14 Jagotec Ag Pharmaceutical tablet capable of liberating one or more drugs at different release rates
US5807579A (en) * 1995-11-16 1998-09-15 F.H. Faulding & Co. Limited Pseudoephedrine combination pharmaceutical compositions
US5824338A (en) * 1996-08-19 1998-10-20 L. Perrigo Company Caplet and gelatin covering therefor
US5830801A (en) * 1997-01-02 1998-11-03 Motorola, Inc. Resistless methods of gate formation in MOS devices
US5830502A (en) * 1994-10-28 1998-11-03 Alza Corporation Injection-molded dosage form
US5830501A (en) * 1991-12-06 1998-11-03 Alza Corporation Dosage form comprising hydrophilic polymer
US5871781A (en) * 1993-09-10 1999-02-16 Fuisz Technologies Ltd. Apparatus for making rapidly-dissolving dosage units
US5912013A (en) * 1991-07-23 1999-06-15 Shire Laboratories, Inc. Advanced drug delivery system and method of treating psychiatric, neurological and other disorders with carbamazepine
US5942034A (en) * 1997-07-24 1999-08-24 Bayer Corporation Apparatus for the gelatin coating of medicaments
US6103260A (en) * 1997-07-17 2000-08-15 Mcneil-Ppc, Inc. Simethicone/anhydrous calcium phosphate compositions
US6103257A (en) * 1998-07-17 2000-08-15 Num-Pop, Inc. System for delivering pharmaceuticals to the buccal mucosa
US6110499A (en) * 1997-07-24 2000-08-29 Alza Corporation Phenytoin therapy
US6117479A (en) * 1995-05-09 2000-09-12 Phoqus Limited Electrostatic coating
US6200590B1 (en) * 1998-08-10 2001-03-13 Naphcare, Inc. Controlled, phased-release suppository and its method of production
US20010001280A1 (en) * 1998-09-09 2001-05-17 Liang-Chang Dong Dosage form comprising liquid formulation
US6248760B1 (en) * 1999-04-14 2001-06-19 Paul C Wilhelmsen Tablet giving rapid release of nicotine for transmucosal administration
US6270805B1 (en) * 1998-11-06 2001-08-07 Andrx Pharmaceuticals, Inc. Two pellet controlled release formulation for water soluble drugs which contains an alkaline metal stearate
US6294200B1 (en) * 1996-02-06 2001-09-25 Jagotec Ag Pharmaceutical tablet suitable to deliver the active substance in subsequent and predeterminable times
US6350398B1 (en) * 1998-09-03 2002-02-26 Basf Aktiengesellschaft Process for producing coated solid dosage forms
US20020028240A1 (en) * 2000-04-17 2002-03-07 Toyohiro Sawada Timed-release compression-coated solid composition for oral administration
US6365185B1 (en) * 1998-03-26 2002-04-02 University Of Cincinnati Self-destructing, controlled release peroral drug delivery system
US20020051807A1 (en) * 2000-01-13 2002-05-02 Joaquina Faour Osmotic device containing alprazolam and an antipsychotic agent
US20030068367A1 (en) * 2001-09-28 2003-04-10 Sowden Harry S. Systems, methods and apparatuses for manufacturing dosage forms
US20030072799A1 (en) * 2001-09-28 2003-04-17 Sowden Harry S. Systems, methods and apparatuses for manufacturing dosage forms
US6555139B2 (en) * 1999-06-28 2003-04-29 Wockhardt Europe Limited Preparation of micron-size pharmaceutical particles by microfluidization
US20030086973A1 (en) * 2001-09-28 2003-05-08 Sowden Harry S Systems, methods and apparatuses for manufacturing dosage forms
US20030124183A1 (en) * 2001-09-28 2003-07-03 Sowden Harry S. Systems, methods and apparatuses for manufacturing dosage forms
US6730646B1 (en) * 1998-07-29 2004-05-04 Reckitt Benckiser N.V. Composition for use in a dishwasher
US6742646B2 (en) * 2001-09-28 2004-06-01 Mcneil-Ppc, Inc. Systems, methods and apparatuses for manufacturing dosage forms

Family Cites Families (343)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US231117A (en) * 1880-08-10 Folding boat
US3371136A (en) * 1968-02-27 United States Borax Chem Detergent tablet forming machine
US542614A (en) * 1895-07-09 Office
US582438A (en) * 1897-05-11 John scheidler
US231129A (en) * 1880-08-10 wiesebrook
US231024A (en) * 1880-08-10 Machine for lining sheets of straw-board
US231163A (en) * 1880-08-17 hamlin
US231062A (en) * 1880-08-10 Felt hat
US966450A (en) * 1909-06-18 1910-08-09 John W S Jones Couch or bed.
US966509A (en) * 1909-06-25 1910-08-09 Charles A Wulf Flushing-valve.
US967414A (en) * 1910-02-11 1910-08-16 William W Hallam Railway-rail.
US966939A (en) * 1910-05-02 1910-08-09 James V Mitchell Sash-lock.
US996497A (en) * 1911-03-30 1911-06-27 Kokomo Sanitary Mfg Co Tank-cover fastener.
US1036647A (en) 1911-06-19 1912-08-27 St Louis Briquette Machine Company Briquet-machine.
US1437816A (en) 1922-07-26 1922-12-05 Howard S Paine Process for preparing fondant or chocolate soft cream centers
US1505827A (en) * 1923-04-25 1924-08-19 Villasenor Eduardo Tablet-making machine
US1900012A (en) * 1925-09-04 1933-03-07 Western Cartridge Co Process of and apparatus for making wads
US2415997A (en) * 1946-01-12 1947-02-18 John W Eldred Article handling apparatus
US2823789A (en) * 1952-05-06 1958-02-18 Gilman Engineering & Mfg Corp Parts feeder ribbon
US2849965A (en) 1954-04-15 1958-09-02 John Holroyd & Company Ltd Machines for use in the production of coated tablets and the like
GB759081A (en) 1954-04-15 1956-10-10 John Holroyd And Company Ltd Improvements relating to machines for the production of coated tablets and the like
US2966431A (en) 1956-03-24 1960-12-27 Basf Ag Separation of filter material from carbon black
US2946298A (en) 1957-11-13 1960-07-26 Arthur Colton Company Compression coating tablet press
US2931276A (en) * 1958-02-10 1960-04-05 Jagenberg Werke Ag Methods of and means for producing, processing, and for treating articles
GB866681A (en) 1958-05-22 1961-04-26 May & Baker Ltd N-substituted piperidines
GB888038A (en) 1959-12-16 1962-01-24 William Warren Triggs C B E Medicinal tablet
GB936386A (en) 1959-01-16 1963-09-11 Wellcome Found Pellets for supplying biologically active substances to ruminants
US2963993A (en) 1959-01-20 1960-12-13 John Holroyd & Company Ltd Machines for making coated tablets by compression
US3096248A (en) 1959-04-06 1963-07-02 Rexall Drug & Chemical Company Method of making an encapsulated tablet
US3029752A (en) * 1959-07-20 1962-04-17 Stokes F J Corp Tablet making machine
GB990784A (en) * 1960-05-23 1965-05-05 Dunlop Rubber Co Improvements in or relating to balls
US3173876A (en) * 1960-05-27 1965-03-16 John C Zobrist Cleaning methods and compositions
GB994742A (en) * 1960-09-09 1965-06-10 Wellcome Found Pharmaceutical tablets containing anthelmintics, and the manufacture thereof
US3108046A (en) 1960-11-25 1963-10-22 Smith Kline French Lab Method of preparing high dosage sustained release tablet and product of this method
NL271831A (fr) * 1960-11-29
US3430535A (en) * 1961-08-25 1969-03-04 Independent Lock Co Key cutter
BE636865A (fr) * 1962-08-31
US3185626A (en) * 1963-03-06 1965-05-25 Sterling Drug Inc Tablet coating method
US3279995A (en) 1963-05-31 1966-10-18 Allen F Reid Shaped pellets
US3276586A (en) * 1963-08-30 1966-10-04 Rosaen Filter Co Indicating means for fluid filters
US3300063A (en) * 1965-01-25 1967-01-24 Mayer & Co Inc O Vacuum gripping apparatus
FR1603314A (en) * 1965-02-23 1971-04-05 Pharmaceutical tablets - having a core and a matrix material
US3328842A (en) * 1965-04-23 1967-07-04 Pentronix Inc Powder compacting press
US3279360A (en) 1965-09-13 1966-10-18 Miehle Goss Dexter Inc Machine for printing on cylindrical articles
US3330400A (en) 1966-03-08 1967-07-11 Miehle Goss Dexter Inc Mechanism for transferring cylindrical articles
GB1212535A (en) * 1966-10-12 1970-11-18 Shionogi & Co Method and apparatus for producing molded article
US3458968A (en) 1966-11-16 1969-08-05 Lester Gregory Jr Dispensing and feed mechanism
GB1144915A (en) * 1966-11-24 1969-03-12 Armour Pharma Improvements in or relating to pastille formulations
US3546142A (en) * 1967-01-19 1970-12-08 Amicon Corp Polyelectrolyte structures
US3656518A (en) * 1967-03-27 1972-04-18 Perry Ind Inc Method and apparatus for measuring and dispensing predetermined equal amounts of powdered material
US3563170A (en) * 1968-04-16 1971-02-16 Reynolds Metals Co Machine for marking the exterior cylindrical surfaces of cans in a continous nonidexing manner
US3605479A (en) 1968-05-08 1971-09-20 Textron Inc Forming press
US3584114A (en) 1968-05-22 1971-06-08 Hoffmann La Roche Free-flowing powders
NL6808619A (fr) 1968-06-19 1969-12-23
US3541006A (en) * 1968-07-03 1970-11-17 Amicon Corp Ultrafiltration process
FR1581088A (fr) 1968-07-17 1969-09-12
US3567043A (en) * 1968-08-05 1971-03-02 Sun Chemical Corp Transfer assembly for use with container printing machines
US3627583A (en) * 1969-04-29 1971-12-14 Sucrest Corp Direct compression vehicles
US3604417A (en) * 1970-03-31 1971-09-14 Wayne Henry Linkenheimer Osmotic fluid reservoir for osmotically activated long-term continuous injector device
US3640654A (en) * 1970-06-25 1972-02-08 Wolverine Pentronix Die and punch assembly for compacting powder and method of assembly
CH569482A5 (fr) 1970-12-23 1975-11-28 Boehringer Sohn Ingelheim
US3811552A (en) * 1971-01-11 1974-05-21 Lilly Co Eli Capsule inspection apparatus and method
US3995631A (en) * 1971-01-13 1976-12-07 Alza Corporation Osmotic dispenser with means for dispensing active agent responsive to osmotic gradient
US3726622A (en) * 1971-08-20 1973-04-10 Wolverine Pentronix Compacting apparatus
DE2157465C3 (de) * 1971-11-19 1975-04-24 Werner & Pfleiderer, 7000 Stuttgart Füllvorrichtung für eine hydraulische Blockpresse
GB1371244A (en) * 1971-12-09 1974-10-23 Howorth Air Conditioning Ltd Machines acting on continuously running textile yarns
BE794951A (fr) * 1972-02-03 1973-05-29 Parke Davis & Co Conditionnement soluble dans l'eau
US3851751A (en) 1972-04-26 1974-12-03 Jones & Co Inc R A Method and apparatus for forming, filling and sealing packages
US3975888A (en) 1972-04-26 1976-08-24 R. A. Jones & Company, Inc. Method and apparatus for forming, filling and sealing packages
US3845770A (en) * 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3912441A (en) 1972-12-13 1975-10-14 Yasuo Shimada Compressing roll in rotary power compression molding machine
US3851638A (en) 1973-02-02 1974-12-03 Kam Act Enterprises Inc Force multiplying type archery bow
DE2309202A1 (de) 1973-02-21 1974-08-29 Schering Ag Arzneiformen mit mikroverkapseltem arzneimittelwirkstoff
US3832525A (en) * 1973-03-26 1974-08-27 Raymond Lee Organization Inc Automatic heating device to prevent freezing of water supply lines
US3916899A (en) * 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US3884143A (en) * 1973-09-04 1975-05-20 Hartnett Co R W Conveyor link for tablet printing apparatus
DE2401419A1 (de) 1974-01-12 1975-07-17 Bosch Gmbh Robert Fahrzeug mit einem hydrostatischen und mechanischen antrieb
US3891375A (en) 1974-01-21 1975-06-24 Vector Corp Tablet press
GB1497044A (en) * 1974-03-07 1978-01-05 Prodotti Antibiotici Spa Salts of phenyl-alkanoic acids
US3988403A (en) * 1974-07-09 1976-10-26 Union Carbide Corporation Process for producing molded structural foam article having a surface that reproducibly and faithfully replicates the surface of the mold
FR2312247A1 (fr) * 1975-05-30 1976-12-24 Parcor Derives de la thieno-pyridine, leur procede de preparation et leurs applications
US4077407A (en) * 1975-11-24 1978-03-07 Alza Corporation Osmotic devices having composite walls
SE414386B (sv) * 1976-03-10 1980-07-28 Aco Laekemedel Ab Sett att framstella och samtidigt forpacka farmaceutiska dosenheter
US4111202A (en) 1976-11-22 1978-09-05 Alza Corporation Osmotic system for the controlled and delivery of agent over time
US4218433A (en) * 1977-03-03 1980-08-19 Nippon Kayaku Kabushiki Kaisha Constant-rate eluting tablet and method of producing same
US4139627A (en) * 1977-10-06 1979-02-13 Beecham Inc. Anesthetic lozenges
DE2752971C2 (de) * 1977-11-28 1982-08-19 Lev Nikolaevič Moskva Koškin Spritzgießmaschine zum Herstellen von Spritzgußteilen aus thermoplastischen Werkstoffen
DE2849494A1 (de) 1978-11-15 1980-05-29 Voss Gunter M Verfahren zur herstellung von arzneimittel-formlingen
US4198390A (en) * 1979-01-31 1980-04-15 Rider Joseph A Simethicone antacid tablet
US4304232A (en) * 1979-03-14 1981-12-08 Alza Corporation Unit system having multiplicity of means for dispensing useful agent
US4271142A (en) * 1979-06-18 1981-06-02 Life Savers, Inc. Portable liquid antacids
US4286497A (en) * 1979-06-18 1981-09-01 Shamah Alfred A Ratchet-securable toggle retainer
JPS5827162B2 (ja) 1979-08-24 1983-06-08 株式会社ヤクルト本社 定速搬送機構
NL7906689A (nl) * 1979-09-06 1981-03-10 Dawsonville Corp Nv Tatoueerinrichting.
DE2936040C2 (de) * 1979-09-06 1982-05-19 Meggle Milchindustrie Gmbh & Co Kg, 8094 Reitmehring Dragierverfahren und Mittel zur Durchführung des Verfahrens, bestehend im wesentlichen aus Saccharose, wenigstens einem weiteren Zucker und Wasser
US4273793A (en) * 1979-10-26 1981-06-16 General Foods Corporation Apparatus and process for the preparation of gasified confectionaries by pressurized injection molding
US4543370A (en) 1979-11-29 1985-09-24 Colorcon, Inc. Dry edible film coating composition, method and coating form
US4318746A (en) * 1980-01-08 1982-03-09 Ipco Corporation Highly stable gel, its use and manufacture
US4292017A (en) 1980-07-09 1981-09-29 Doepel Wallace A Apparatus for compressing tablets
US4362757A (en) 1980-10-22 1982-12-07 Amstar Corporation Crystallized, readily water dispersible sugar product containing heat sensitive, acidic or high invert sugar substances
FR2492661A1 (fr) * 1980-10-28 1982-04-30 Laruelle Claude Nouvelle forme galenique d'administration du metoclopramide, son procede de preparation et medicament comprenant cette nouvelle forme
US4683256A (en) * 1980-11-06 1987-07-28 Colorcon, Inc. Dry edible film coating composition, method and coating form
US4327076A (en) * 1980-11-17 1982-04-27 Life Savers, Inc. Compressed chewable antacid tablet and method for forming same
US4327725A (en) * 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
US4340054A (en) * 1980-12-29 1982-07-20 Alza Corporation Dispenser for delivering fluids and solids
IE53102B1 (en) * 1981-05-12 1988-06-22 Ici Plc Pharmaceutical spiro-succinimide derivatives
DE3144678A1 (de) 1981-11-10 1983-05-19 Eugen Dipl.-Ing. 8871 Burtenbach Bühler Verfahren und einrichtung zur herstellung von formlingen aus einer rieselfaehigen masse
JPS58152813A (ja) * 1982-03-08 1983-09-10 Sumitomo Chem Co Ltd 鮮明な刻印を有する錠剤およびその製法
US4449983A (en) * 1982-03-22 1984-05-22 Alza Corporation Simultaneous delivery of two drugs from unit delivery device
DK151608C (da) * 1982-08-13 1988-06-20 Benzon As Alfred Fremgangsmaade til fremstilling af et farmaceutisk peroralt polydepotpraeparat med kontrolleret afgivelse
US4517205A (en) * 1983-01-03 1985-05-14 Nabisco Brands, Inc. Co-deposited two-component hard candy
US4533345A (en) * 1983-06-14 1985-08-06 Fertility & Genetics Associates Uterine catheter
FR2548675B1 (fr) * 1983-07-06 1987-01-09 Seppic Sa Compositions filmogenes pour enrobage des formes solides de produits pharmaceutiques ou alimentaires et produits obtenus revetus desdites compositions
AU591171B2 (en) 1983-11-02 1989-11-30 Alza Corporation Dispenser for delivering thermo-responsive composition
NL194820C (nl) 1983-11-02 2003-04-03 Alza Corp Preparaat voor de afgifte van een op warmte reagerende samenstelling.
DE3404108A1 (de) * 1984-02-07 1985-08-14 Kilian & Co GmbH, 5000 Köln Tablettenpresse
US4564525A (en) * 1984-03-30 1986-01-14 Mitchell Cheryl R Confection products
JPS60217106A (ja) * 1984-04-12 1985-10-30 高橋　信之 無機粉末凍結成形法
US4528335A (en) * 1984-05-18 1985-07-09 Phillips Petroleum Company Polymer blends
US4610884A (en) * 1984-06-29 1986-09-09 The Procter & Gamble Company Confectionery cremes
US4828841A (en) * 1984-07-24 1989-05-09 Colorcon, Inc. Maltodextrin coating
US4643894A (en) * 1984-07-24 1987-02-17 Colorcon, Inc. Maltodextrin coating
US4894234A (en) * 1984-10-05 1990-01-16 Sharma Shri C Novel drug delivery system for antiarrhythmics
JPS61100519A (ja) * 1984-10-23 1986-05-19 Shin Etsu Chem Co Ltd 医薬用硬質カプセル
US4684534A (en) * 1985-02-19 1987-08-04 Dynagram Corporation Of America Quick-liquifying, chewable tablet
US4874614A (en) * 1985-03-25 1989-10-17 Abbott Laboratories Pharmaceutical tableting method
US4627971A (en) * 1985-04-22 1986-12-09 Alza Corporation Osmotic device with self-sealing passageway
CA1234717A (fr) * 1985-06-28 1988-04-05 Leslie F. Knebl Gomme a macher humide
GB8517073D0 (en) 1985-07-05 1985-08-14 Hepworth Iron Co Ltd Pipe pipe couplings &c
GB8518301D0 (en) * 1985-07-19 1985-08-29 Fujisawa Pharmaceutical Co Hydrodynamically explosive systems
US4665116A (en) 1985-08-28 1987-05-12 Turtle Wax, Inc. Clear cleaner/polish composition
US4663147A (en) * 1985-09-03 1987-05-05 International Minerals & Chemical Corp. Disc-like sustained release formulation
US4898733A (en) * 1985-11-04 1990-02-06 International Minerals & Chemical Corp. Layered, compression molded device for the sustained release of a beneficial agent
US4853249A (en) 1985-11-15 1989-08-01 Taisho Pharmaceutical Co., Ltd. Method of preparing sustained-release pharmaceutical/preparation
DE3601516A1 (de) * 1986-01-20 1987-07-23 Agie Ag Ind Elektronik Lichtschranke
JPS62230600A (ja) 1986-03-31 1987-10-09 東洋ゴム工業株式会社 伸縮可能なフオ−クを備えたフオ−クリフト
DE3610878A1 (de) 1986-04-01 1987-10-08 Boehringer Ingelheim Kg Formlinge aus pellets
US4873231A (en) 1986-04-08 1989-10-10 Smith Walton J Decreasing the toxicity of an ibuprofen salt
SE8601624D0 (sv) * 1986-04-11 1986-04-11 Haessle Ab New pharmaceutical preparations
US4857330A (en) * 1986-04-17 1989-08-15 Alza Corporation Chlorpheniramine therapy
GB2189698A (en) 1986-04-30 1987-11-04 Haessle Ab Coated omeprazole tablets
US4960416A (en) * 1986-04-30 1990-10-02 Alza Corporation Dosage form with improved delivery capability
GB2189699A (en) * 1986-04-30 1987-11-04 Haessle Ab Coated acid-labile medicaments
US5200196A (en) * 1986-05-09 1993-04-06 Alza Corporation Improvement in pulsed drug therapy
US4802924A (en) * 1986-06-19 1989-02-07 Colorcon, Inc. Coatings based on polydextrose for aqueous film coating of pharmaceutical food and confectionary products
DE3629994A1 (de) 1986-09-03 1988-03-17 Weissenbacher Ernst Rainer Pro Vorrichtung zur medikamentenapplikation in koerperhoehlen bzw. auf koerperoberflaechen
US4803076A (en) * 1986-09-04 1989-02-07 Pfizer Inc. Controlled release device for an active substance
CA1290526C (fr) 1986-11-07 1991-10-15 Marianne Wieser Fonctionnement de matrice et poincon
DE3640574A1 (de) 1986-11-27 1988-06-09 Katjes Fassin Gmbh & Co Kg Verfahren zur herstellung eines essbaren pralinenfoermigen produktes und vorrichtung fuer die durchfuehrung des verfahrens
US4828845A (en) * 1986-12-16 1989-05-09 Warner-Lambert Company Xylitol coated comestible and method of preparation
IT1201136B (it) 1987-01-13 1989-01-27 Resa Farma Compressa per uso farmaceutico atta al rilascio in tempi successivi di sostanze attive
US4801461A (en) * 1987-01-28 1989-01-31 Alza Corporation Pseudoephedrine dosage form
US5200193A (en) 1987-04-22 1993-04-06 Mcneilab, Inc. Pharmaceutical sustained release matrix and process
US4808413A (en) * 1987-04-28 1989-02-28 E. R. Squibb & Sons, Inc. Pharmaceutical compositions in the form of beadlets and method
US4792448A (en) 1987-06-11 1988-12-20 Pfizer Inc. Generic zero order controlled drug delivery system
US4813818A (en) * 1987-08-25 1989-03-21 Michael Sanzone Apparatus and method for feeding powdered materials
US4978483A (en) 1987-09-28 1990-12-18 Redding Bruce K Apparatus and method for making microcapsules
US4996061A (en) * 1987-10-07 1991-02-26 Merrell Dow Pharmaceuticals Inc. Pharmaceutical composition for piperidinoalkanol-decongestant combination
CA1330886C (fr) 1988-01-22 1994-07-26 Bend Research Inc. Systeme controle par la pression osmotique servant a la distribution de solutions diluees
US5279660A (en) * 1988-05-24 1994-01-18 Berol Nobel Stenungsund Ab Use of viscosity-adjusting agent to counteract viscosity decrease upon temperature increase of a water-based system
US4999226A (en) * 1988-06-01 1991-03-12 Merrell Dow Pharmaceuticals Inc. Pharmaceutical compositions for piperidinoalkanol-ibuprofen combination
DE3822095A1 (de) * 1988-06-30 1990-01-04 Klinge Co Chem Pharm Fab Neue arzneimittelformulierung sowie verfahren zu deren herstellung
GB8820353D0 (en) * 1988-08-26 1988-09-28 Staniforth J N Controlled release tablet
US5194464A (en) * 1988-09-27 1993-03-16 Takeda Chemical Industries, Ltd. Enteric film and preparatoin thereof
JPH0816051B2 (ja) 1988-12-07 1996-02-21 エスエス製薬株式会社 徐放性坐剤
US5610214A (en) * 1988-12-29 1997-03-11 Deknatel Technology Corporation, Inc. Method for increasing the rate of absorption of polycaprolactone
IL92966A (en) * 1989-01-12 1995-07-31 Pfizer Hydrogel-operated release devices
US5030452A (en) * 1989-01-12 1991-07-09 Pfizer Inc. Dispensing devices powered by lyotropic liquid crystals
US5032406A (en) * 1989-02-21 1991-07-16 Norwich Eaton Pharmaceuticals, Inc. Dual-action tablet
US5006297A (en) * 1989-02-22 1991-04-09 Acushnet Company Method of molding polyurethane covered golf balls
US4956182A (en) 1989-03-16 1990-09-11 Bristol-Myers Company Direct compression cholestyramine tablet and solvent-free coating therefor
US4931286A (en) * 1989-04-19 1990-06-05 Aqualon Company High gloss cellulose tablet coating
NZ233403A (en) * 1989-04-28 1992-09-25 Mcneil Ppc Inc Simulated capsule-like medicament
US4990535A (en) * 1989-05-03 1991-02-05 Schering Corporation Pharmaceutical composition comprising loratadine, ibuprofen and pseudoephedrine
US4992277A (en) * 1989-08-25 1991-02-12 Schering Corporation Immediate release diltiazem formulation
EP0419410A3 (en) * 1989-09-19 1991-08-14 Ciba-Geigy Ag Alkanophenones
US5178878A (en) * 1989-10-02 1993-01-12 Cima Labs, Inc. Effervescent dosage form with microparticles
US5223264A (en) * 1989-10-02 1993-06-29 Cima Labs, Inc. Pediatric effervescent dosage form
JPH03139496A (ja) * 1989-10-25 1991-06-13 Sanshin Ind Co Ltd 船舶推進機
US5169645A (en) 1989-10-31 1992-12-08 Duquesne University Of The Holy Ghost Directly compressible granules having improved flow properties
FR2655266B1 (fr) * 1989-12-05 1992-04-03 Smith Kline French Lab Compositions pharmaceutiques a base de cimetidine.
US5100676A (en) * 1990-02-02 1992-03-31 Biosurface Technology, Inc. Cool storage of cultured epithelial sheets
US5158777A (en) * 1990-02-16 1992-10-27 E. R. Squibb & Sons, Inc. Captopril formulation providing increased duration of activity
US4980169A (en) * 1990-05-03 1990-12-25 Warner-Lambert Company Flavor enhancing and increasing efficacy of cough drops
US4983394A (en) 1990-05-03 1991-01-08 Warner-Lambert Company Flavor enhancing and medicinal taste masking agent
US5075114A (en) * 1990-05-23 1991-12-24 Mcneil-Ppc, Inc. Taste masking and sustained release coatings for pharmaceuticals
US5133892A (en) 1990-10-17 1992-07-28 Lever Brothers Company, Division Of Conopco, Inc. Machine dishwashing detergent tablets
US5683719A (en) * 1990-11-22 1997-11-04 British Technology Group Limited Controlled release compositions
US5098715A (en) * 1990-12-20 1992-03-24 Burroughs Wellcome Co. Flavored film-coated tablet
US5232706A (en) * 1990-12-31 1993-08-03 Esteve Quimica, S.A. Oral pharmaceutical preparation containing omeprazol
DE4101873C2 (de) * 1991-01-23 1993-12-09 Isis Pharma Gmbh Peroral applizierbare Arzneiform zur Behandlung zentraler Dopaminmangelzustände
US5378475A (en) 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
CA2061520C (fr) * 1991-03-27 2003-04-22 Lawrence J. Daher Systeme de delivrance accelerant l'effet et accroissant la puissance
YU48263B (sh) 1991-06-17 1997-09-30 Byk Gulden Lomberg Chemische Fabrik Gmbh. Postupak za dobijanje farmaceutskog preparata na bazi pantoprazola
US5314696A (en) * 1991-06-27 1994-05-24 Paulos Manley A Methods for making and administering a blinded oral dosage form and blinded oral dosage form therefor
US5252338A (en) * 1991-06-27 1993-10-12 Alza Corporation Therapy delayed
US5190927A (en) * 1991-07-09 1993-03-02 Merck & Co., Inc. High-glyceryl, low-acetyl gellan gum for non-brittle gels
US5405617A (en) * 1991-11-07 1995-04-11 Mcneil-Ppc, Inc. Aliphatic or fatty acid esters as a solventless carrier for pharmaceuticals
US5407686A (en) * 1991-11-27 1995-04-18 Sidmak Laboratories, Inc. Sustained release composition for oral administration of active ingredient
DK171536B1 (da) 1991-12-06 1996-12-23 Rasmussen Kann Ind As Vindue med ramme af ekstruderede profilemner
US5200194A (en) * 1991-12-18 1993-04-06 Alza Corporation Oral osmotic device
GB2284760B (en) 1993-11-23 1998-06-24 Euro Celtique Sa A method of preparing pharmaceutical compositions by melt pelletisation
KR940703886A (ko) * 1992-01-17 1994-12-12 토머스 디. 뵈닝 셀룰로오스 중합체 및 락토오스 기재 필름 코팅 조성물 및 필름 코팅(Film Coatings and Film Coating Compositions Based on Cellulosic Polymers and Lactose)
US5427614A (en) * 1992-02-14 1995-06-27 Warner-Lambert Company Starch based formulations
US5209746A (en) * 1992-02-18 1993-05-11 Alza Corporation Osmotically driven delivery devices with pulsatile effect
US5221278A (en) * 1992-03-12 1993-06-22 Alza Corporation Osmotically driven delivery device with expandable orifice for pulsatile delivery effect
US5656296A (en) * 1992-04-29 1997-08-12 Warner-Lambert Company Dual control sustained release drug delivery systems and methods for preparing same
US5260068A (en) * 1992-05-04 1993-11-09 Anda Sr Pharmaceuticals Inc. Multiparticulate pulsatile drug delivery system
GR1002332B (el) 1992-05-21 1996-05-16 Mcneil-Ppc Inc. Νεες φαρμακευτικες συνθεσεις που περιεχουν σιμεθεικονη.
EP0572731A1 (fr) 1992-06-01 1993-12-08 The Procter & Gamble Company Composition à mâcher contenant un agent de décongestion
WO1994007470A1 (fr) * 1992-09-30 1994-04-14 Pfizer Inc. Article contenant un noyau et un revetement d'epaisseur non constante
ES2194863T3 (es) * 1992-11-30 2003-12-01 Kv Pharm Co Materiales farmaceuticos con enmascarado de sabor.
US5375963A (en) 1993-01-19 1994-12-27 Wohlwend; Clayton E. Multipurpose lifting apparatus
JP2524955B2 (ja) 1993-04-22 1996-08-14 トーワ株式会社 電子部品の樹脂封止成形方法及び装置
NZ260408A (en) 1993-05-10 1996-05-28 Euro Celtique Sa Controlled release preparation comprising tramadol
IT1264855B1 (it) * 1993-06-21 1996-10-17 Zambon Spa Composizioni farmaceutiche contenenti sali dell'acido s(+)-2-(4-isobutilfenil) propionico con amminoacidi basici
ZA944949B (en) 1993-07-12 1995-04-05 Smithkline Beecham Corp Matrix-entrapped beadlet preparation
US5518551A (en) * 1993-09-10 1996-05-21 Fuisz Technologies Ltd. Spheroidal crystal sugar and method of making
US5397574A (en) * 1993-10-04 1995-03-14 Andrx Pharmaceuticals, Inc. Controlled release potassium dosage form
US5433951A (en) * 1993-10-13 1995-07-18 Bristol-Myers Squibb Company Sustained release formulation containing captopril and method
US5500227A (en) * 1993-11-23 1996-03-19 Euro-Celtique, S.A. Immediate release tablet cores of insoluble drugs having sustained-release coating
DE4341442C2 (de) 1993-12-04 1998-11-05 Lohmann Therapie Syst Lts Vorrichtung zur kontrollierten Freisetzung von Wirkstoffen sowie ihre Verwendung
US5458887A (en) * 1994-03-02 1995-10-17 Andrx Pharmaceuticals, Inc. Controlled release tablet formulation
US5453920A (en) * 1994-03-08 1995-09-26 Eubanks; William W. Trouble light having a shroud with see-through opening
US5559110A (en) 1994-03-09 1996-09-24 The Dupont Merck Pharmaceutical Company Pharmaceutical formulations of cyclic urea type compounds
JPH07281423A (ja) * 1994-04-07 1995-10-27 Konica Corp 印刷版の製版方法
US6020002A (en) * 1994-06-14 2000-02-01 Fuisz Technologies Ltd. Delivery of controlled-release system(s)
SE9402431D0 (sv) * 1994-07-08 1994-07-08 Astra Ab New tablet formulation
ES2100142T3 (es) 1994-07-08 2002-03-01 Astrazeneca Ab Forma de dosificacion en tabletas i constituida por unidades multiples.
US5788979A (en) * 1994-07-22 1998-08-04 Inflow Dynamics Inc. Biodegradable coating with inhibitory properties for application to biocompatible materials
US5849327A (en) 1994-07-29 1998-12-15 Advanced Polymer Systems, Inc. Delivery of drugs to the lower gastrointestinal tract
WO1996004128A1 (fr) * 1994-08-03 1996-02-15 Voss Gunter M Procede de fabrication de comprimes enrobes
DE9414065U1 (de) * 1994-08-31 1994-11-03 Roehm Gmbh Thermoplastischer Kunststoff für darmsaftlösliche Arznei-Umhüllungen
DE4431653C2 (de) * 1994-09-06 2000-01-20 Lohmann Therapie Syst Lts Manteltablette zur kontrollierten Freisetzung von Wirkstoffen, ein Verfahren zu ihrer Herstellung und ihre Verwendung
US5733575A (en) * 1994-10-07 1998-03-31 Bpsi Holdings, Inc. Enteric film coating compositions, method of coating therewith, and coated forms
CA2134611C (fr) * 1994-10-28 2002-12-24 Richard John Yarwood Procede de preparation de formes posologiques solides
US5593696A (en) * 1994-11-21 1997-01-14 Mcneil-Ppc, Inc. Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders
US5756123A (en) * 1994-12-01 1998-05-26 Japan Elanco Co., Ltd. Capsule shell
US5626896A (en) * 1994-12-09 1997-05-06 A.E. Staley Manufacturing Co. Method for making liquid-centered jelly candies
US5582838A (en) * 1994-12-22 1996-12-10 Merck & Co., Inc. Controlled release drug suspension delivery device
DE4446468A1 (de) * 1994-12-23 1996-06-27 Basf Ag Verfahren zur Herstellung von umhüllten Tabletten
US6471994B1 (en) * 1995-01-09 2002-10-29 Edward Mendell Co., Inc. Pharmaceutical excipient having improved compressibility
ES2094694B1 (es) * 1995-02-01 1997-12-16 Esteve Quimica Sa Nueva formulacion farmaceuticamente estable de un compuesto de bencimidazol y su proceso de obtencion.
EP0726216B1 (fr) * 1995-02-07 1998-09-09 Hermann Kronseder Roue de transport en forme d'étoile pour récipients
SE9500478D0 (sv) * 1995-02-09 1995-02-09 Astra Ab New pharmaceutical formulation and process
US5736159A (en) * 1995-04-28 1998-04-07 Andrx Pharmaceuticals, Inc. Controlled release formulation for water insoluble drugs in which a passageway is formed in situ
US5558879A (en) 1995-04-28 1996-09-24 Andrx Pharmaceuticals, Inc. Controlled release formulation for water soluble drugs in which a passageway is formed in situ
US5827874A (en) 1995-05-05 1998-10-27 Meyer; Hans Methods of treating pain and inflammation with proline
ES2129902T3 (es) * 1995-05-13 1999-06-16 Hermann Kronseder Rueda transportadora en estrella para recipientes.
US5627971A (en) * 1995-06-01 1997-05-06 Northern Telecom Limited Machine method for determining the eligibility of links in a network
US5654005A (en) * 1995-06-07 1997-08-05 Andrx Pharmaceuticals, Inc. Controlled release formulation having a preformed passageway
DE69618956T2 (de) * 1995-06-09 2002-08-22 Scherer Technologies Inc R P Weichgelatinekapsel mit teilchenmaterial
GB9517031D0 (en) * 1995-08-19 1995-10-25 Procter & Gamble Confection compositions
PT859612E (pt) * 1995-09-21 2003-10-31 Pharma Pass Ii Llc Composicao farmaceutica contendo um omeprazol acid-labil e um processo para a sua preparacao
AUPN605795A0 (en) * 1995-10-19 1995-11-09 F.H. Faulding & Co. Limited Analgesic pharmaceutical composition
DE19539361A1 (de) 1995-10-23 1997-04-24 Basf Ag Verfahren zur Herstellung von mehrschichtigen, festen Arzneiformen zur oralen oder rektalen Verabreichung
IT1279673B1 (it) * 1995-11-07 1997-12-16 Acma Spa Apparecchiatura e metodo per la formazione di gruppi ordinati di prodotti da alimentare a passo.
US5733578A (en) * 1995-11-15 1998-03-31 Edward Mendell Co., Inc. Directly compressible high load acetaminophen formulations
JP3220373B2 (ja) * 1995-11-28 2001-10-22 バイエル薬品株式会社 持続性ニフエジピン製剤
US6489346B1 (en) 1996-01-04 2002-12-03 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
SE9600070D0 (sv) 1996-01-08 1996-01-08 Astra Ab New oral pharmaceutical dosage forms
SE9600071D0 (sv) 1996-01-08 1996-01-08 Astra Ab New oral formulation of two active ingredients I
US5879728A (en) * 1996-01-29 1999-03-09 Warner-Lambert Company Chewable confectionary composition and method of preparing same
US6245351B1 (en) * 1996-03-07 2001-06-12 Takeda Chemical Industries, Ltd. Controlled-release composition
US5711691A (en) * 1996-05-13 1998-01-27 Air Packaging Technologies, Inc. Self-closing and self-sealing valve device for use with inflatable structures
US5827535A (en) 1996-06-21 1998-10-27 Banner Pharmacaps, Inc. Graphically impressed softgel and method for making same
US5797898A (en) 1996-07-02 1998-08-25 Massachusetts Institute Of Technology Microchip drug delivery devices
US5916881A (en) * 1996-10-07 1999-06-29 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo High trehalose content syrup
US5807580A (en) 1996-10-30 1998-09-15 Mcneil-Ppc, Inc. Film coated tablet compositions having enhanced disintegration characteristics
US6077539A (en) * 1996-11-12 2000-06-20 Pozen, Inc. Treatment of migraine headache
GB9624110D0 (en) * 1996-11-20 1997-01-08 Molins Plc Transferring rod like articles
DE19710213A1 (de) * 1997-03-12 1998-09-17 Basf Ag Verfahren zur Herstellung von festen Kombinationsarzneiformen
US6210710B1 (en) * 1997-04-28 2001-04-03 Hercules Incorporated Sustained release polymer blend for pharmaceutical applications
US5837301A (en) 1997-04-28 1998-11-17 Husky Injection Molding Systems Ltd. Injection molding machine having a high speed turret
US6149939A (en) * 1997-05-09 2000-11-21 Strumor; Mathew A. Healthful dissolvable oral tablets, and mini-bars
AU7375598A (en) * 1997-05-09 1998-11-27 Sage Pharmaceuticals, Inc. Stable oral pharmaceutical dosage forms
AU7755398A (en) * 1997-06-25 1999-01-19 Ipr-Institute For Pharmaceutical Research Ag Method for reducing body weight
US6517866B1 (en) * 1997-07-01 2003-02-11 Pfizer Inc. Sertraline salts and sustained-release dosage forms of sertraline
DE59812488D1 (de) 1997-07-09 2005-02-17 Swiss Caps Rechte & Lizenzen Verfahren und vorrichtung zum herstellen einer mehrschichtigen, physiologisch verträglichen darreichungsform
DE19733505A1 (de) * 1997-08-01 1999-02-04 Knoll Ag Schnell wirksames Analgeticum
US6174548B1 (en) * 1998-08-28 2001-01-16 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6096340A (en) 1997-11-14 2000-08-01 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6602522B1 (en) 1997-11-14 2003-08-05 Andrx Pharmaceuticals L.L.C. Pharmaceutical formulation for acid-labile compounds
PT1035834E (pt) * 1997-12-05 2002-09-30 Alza Corp Forma de dosagem osmotica que compreende primeiro e segundo revestimentos
US6485748B1 (en) * 1997-12-12 2002-11-26 Andrx Pharmaceuticals, Inc. Once daily pharmaceutical tablet having a unitary core
US6022554A (en) * 1997-12-15 2000-02-08 American Home Products Corporation Polymeric microporous film coated subcutaneous implant
US6475510B1 (en) 1997-12-19 2002-11-05 Smithkline Beecham Corporation Process for manufacturing bite-dispersion tablets
US6432442B1 (en) * 1998-02-23 2002-08-13 Mcneil-Ppc, Inc. Chewable product
US6110500A (en) * 1998-03-25 2000-08-29 Temple University Coated tablet with long term parabolic and zero-order release kinetics
US6372254B1 (en) * 1998-04-02 2002-04-16 Impax Pharmaceuticals Inc. Press coated, pulsatile drug delivery system suitable for oral administration
ATE313422T1 (de) * 1998-05-01 2006-01-15 Duramed Pharmaceuticals Inc Verfahren zur spritzgussherstellung von vorrichtungen mit kontrollierter wirkstofffreisetzung und damit hergestellte vorrichtung
US6365183B1 (en) * 1998-05-07 2002-04-02 Alza Corporation Method of fabricating a banded prolonged release active agent dosage form
TW592730B (en) 1998-05-15 2004-06-21 Chugai Pharmaceutical Co Ltd Controlled release formulations
UA69413C2 (uk) * 1998-05-22 2004-09-15 Брістол-Майерс Сквібб Компані Фармацевтична композиція, яка містить серцевину та ентеросолюбільну оболонку, фармацевтична композиція у вигляді сфероїдальних гранул, спосіб одержання сфероїдальних гранул та спосіб одержання фармацевтичної композиції
KR20080083074A (ko) 1998-06-03 2008-09-12 알자 코포레이션 연장된 약물 치료를 제공하기 위한 방법 및 장치
US6106267A (en) * 1998-06-05 2000-08-22 Aylward; John T. Apparatus for forming a compression-molded product
US6099865A (en) * 1998-07-08 2000-08-08 Fmc Corporation Croscarmellose taste masking
UA73092C2 (uk) * 1998-07-17 2005-06-15 Брістол-Майерс Сквібб Компані Таблетка з ентеросолюбільним покриттям і спосіб її приготування
FR2781152B1 (fr) * 1998-07-20 2001-07-06 Permatec Tech Ag Utilisation d'un polymere de type acrylique en tant qu'agent de desagregation
US5997905A (en) * 1998-09-04 1999-12-07 Mcneil-Ppc Preparation of pharmaceutically active particles
US6602521B1 (en) * 1998-09-29 2003-08-05 Impax Pharmaceuticals, Inc. Multiplex drug delivery system suitable for oral administration
US6322819B1 (en) * 1998-10-21 2001-11-27 Shire Laboratories, Inc. Oral pulsed dose drug delivery system
JP3449253B2 (ja) * 1998-10-29 2003-09-22 シオノギクオリカプス株式会社 硬質カプセルの製造方法
US6165512A (en) 1998-10-30 2000-12-26 Fuisz Technologies Ltd. Dosage forms containing taste masked active agents
SE9803772D0 (sv) 1998-11-05 1998-11-05 Astra Ab Pharmaceutical formulation
US6183681B1 (en) * 1998-12-07 2001-02-06 Centurion International, Inc. Multi-stage insert molding method
DE59901613D1 (de) * 1999-02-10 2002-07-11 Suwelack Skin & Health Care Ag Beta-1,3-Glucan aus Euglena enthaltendes gefriergetrocknetes Erzeugnis, seine Herstellung und Verwendung
US6274162B1 (en) 2000-01-14 2001-08-14 Bpsi Holdings, Inc. Elegant film coating system
US6248361B1 (en) * 1999-02-26 2001-06-19 Integ, Ltd. Water-soluble folic acid compositions
DE19913692A1 (de) * 1999-03-25 2000-09-28 Basf Ag Mechanisch stabile pharmazeutische Darreichungsformen, enthaltend flüssige oder halbfeste oberflächenaktive Substanzen
US6090401A (en) * 1999-03-31 2000-07-18 Mcneil-Ppc, Inc. Stable foam composition
JP3716901B2 (ja) * 1999-04-14 2005-11-16 シオノギクオリカプス株式会社 セルロースエーテルフィルム
DE19925710C2 (de) 1999-06-07 2002-10-10 Byk Gulden Lomberg Chem Fab Neue Zubereitung und Darreichungsform enthaltend einen säurelabilen Protonenpumpenhemmer
US6375963B1 (en) 1999-06-16 2002-04-23 Michael A. Repka Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof
US20020102309A1 (en) * 1999-09-14 2002-08-01 Jane C. I. Hirsh Controlled release formulation for administration of an anti-inflammatory naphthalene derivative
DE19954420A1 (de) * 1999-11-12 2001-05-31 Lohmann Therapie Syst Lts Zubereitung, bestehend aus einer film-, folien- oder oblatenförmigen Darreichungsform mit zweischichtigem Aufbau und integrierter Kennzeichnung
DE19960494A1 (de) * 1999-12-15 2001-06-21 Knoll Ag Vorrichtung und Verfahren zum Herstellen von festen wirkstoffhaltigen Formen
WO2001047498A2 (fr) * 1999-12-23 2001-07-05 Pfizer Products Inc. Forme de dosage d'un medicament stratifie entraine par un hydrogel
DE19963569B4 (de) * 1999-12-29 2006-11-16 Reckitt Benckiser N.V. Zusammensetzung zur Verwendung in einer Geschirrspülmaschine
US6627223B2 (en) 2000-02-11 2003-09-30 Eurand Pharmaceuticals Ltd. Timed pulsatile drug delivery systems
FR2807034B1 (fr) 2000-03-29 2002-06-14 Roquette Freres Mannitol pulverulent et son procede de fabrication
US6372252B1 (en) * 2000-04-28 2002-04-16 Adams Laboratories, Inc. Guaifenesin sustained release formulation and tablets
GB2362350A (en) 2000-05-11 2001-11-21 Reckitt Benekiser N V Process and press for the production of tablets
US20030086972A1 (en) 2000-08-09 2003-05-08 Appel Leah E. Hydrogel-driven drug dosage form
US6727200B2 (en) * 2000-08-31 2004-04-27 Mra Laboratories, Inc. High dielectric constant very low fired X7R ceramic capacitor, and powder for making
AU2001288938A1 (en) * 2000-09-07 2002-03-22 Akpharma Inc. Edible candy compositions and methods of using the same
GB0027471D0 (en) * 2000-11-08 2000-12-27 Smithkline Beecham Plc Processes
WO2002066015A1 (fr) 2001-02-16 2002-08-29 Bristol-Myers Squibb Pharma Company Utilisation de polymeres de polyalkylamine dans des dispositifs a liberation regulee
US20030070584A1 (en) * 2001-05-15 2003-04-17 Cynthia Gulian Dip coating compositions containing cellulose ethers
WO2003007917A1 (fr) 2001-07-16 2003-01-30 Astrazeneca Ab Formulation pharmaceutique a base d'un inhibiteur de la pompe a proton et d'antiacides
US6558722B2 (en) * 2001-07-18 2003-05-06 Wm. Wrigley Jr. Company Use of powdered gum in making a coating for a confection
GB0120835D0 (en) 2001-08-28 2001-10-17 Smithkline Beecham Plc Process
US20030059466A1 (en) * 2001-09-14 2003-03-27 Pawan Seth Delayed release tablet of venlafaxin
US7323192B2 (en) * 2001-09-28 2008-01-29 Mcneil-Ppc, Inc. Immediate release tablet
JP2005529059A (ja) 2001-09-28 2005-09-29 マクニール−ピーピーシー・インコーポレイテッド 改質した放出用の投薬形態
US20030066068A1 (en) * 2001-09-28 2003-04-03 Koninklijke Philips Electronics N.V. Individual recommender database using profiles of others
US20040006111A1 (en) 2002-01-25 2004-01-08 Kenneth Widder Transmucosal delivery of proton pump inhibitors
US7790215B2 (en) 2002-03-26 2010-09-07 Purdue Pharma Lp Sustained-release gel coated compositions
EP1372040B1 (fr) 2002-06-11 2008-03-05 ASML Netherlands B.V. Appareil lithographique et méthode pour la fabrication d'un dispositif
TW578439B (en) * 2002-10-25 2004-03-01 Ritdisplay Corp Organic light emitting diode and material applied in the organic light emitting diode
US20050008695A1 (en) * 2003-05-21 2005-01-13 Control Delivery Systems, Inc. Compositions and methods for delivering a biologically active agent
US20050074514A1 (en) * 2003-10-02 2005-04-07 Anderson Oliver B. Zero cycle molding systems, methods and apparatuses for manufacturing dosage forms
NZ589750A (en) 2004-10-21 2012-07-27 Aptalis Pharmatech Inc Taste-masked pharmaceutical compositions with gastrosoluble pore-formers

Patent Citations (99)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US599865A (en) * 1898-03-01 Emanuel l
US2307371A (en) * 1941-08-13 1943-01-05 Ray O Vac Co Molding process
US2996431A (en) * 1953-12-16 1961-08-15 Barry Richard Henry Friable tablet and process for manufacturing same
US3146169A (en) * 1960-01-21 1964-08-25 Burroughs Wellcome Co Pharmaceutical formulations and their manufacture
US3085942A (en) * 1960-12-28 1963-04-16 Hoffmann La Roche Antitussive compositions and preparation
US3832252A (en) * 1970-09-29 1974-08-27 T Higuchi Method of making a drug-delivery device
US3760804A (en) * 1971-01-13 1973-09-25 Alza Corp Improved osmotic dispenser employing magnesium sulphate and magnesium chloride
US4139589A (en) * 1975-02-26 1979-02-13 Monique Beringer Process for the manufacture of a multi-zone tablet and tablet manufactured by this process
US4230693A (en) * 1975-04-21 1980-10-28 Armour-Dial, Inc. Antacid tablets and processes for their preparation
US4097606A (en) * 1975-10-08 1978-06-27 Bristol-Myers Company APAP Tablet containing an alkali metal carboxymethylated starch and processes for manufacturing same
US4371516A (en) * 1976-10-06 1983-02-01 John Wyeth & Brother Limited Articles for carrying chemicals
US4425332A (en) * 1978-09-21 1984-01-10 Beecham Group Limited Antacid composition
US4173626A (en) * 1978-12-11 1979-11-06 Merck & Co., Inc. Sustained release indomethacin
US4271206A (en) * 1979-10-26 1981-06-02 General Foods Corporation Gasified candy having a predetermined shape
US4473526A (en) * 1980-01-23 1984-09-25 Eugen Buhler Method of manufacturing dry-pressed molded articles
US5002970A (en) * 1981-07-31 1991-03-26 Eby Iii George A Flavor masked ionizable zinc compositions for oral absorption
US4372942A (en) * 1981-08-13 1983-02-08 Beecham Inc. Candy base and liquid center hard candy made therefrom
US4576604A (en) * 1983-03-04 1986-03-18 Alza Corporation Osmotic system with instant drug availability
US4882167A (en) * 1983-05-31 1989-11-21 Jang Choong Gook Dry direct compression compositions for controlled release dosage forms
US4749575A (en) * 1983-10-03 1988-06-07 Bio-Dar Ltd. Microencapsulated medicament in sweet matrix
US4781714A (en) * 1983-11-02 1988-11-01 Alza Corporation Dispenser for delivering thermo-responsive composition
US4518335A (en) * 1984-03-14 1985-05-21 Allied Corporation Dilatant mold and dilatant molding apparatus
US4661521A (en) * 1984-04-30 1987-04-28 Mallinckrodt, Inc. Direct tableting acetaminophen compositions
US4666212A (en) * 1984-06-15 1987-05-19 Crucible S.A. Metal value recovery
US4686212A (en) * 1985-08-13 1987-08-11 Pharmacontrol Corp. Stable sodium aspirin tablet compositions
US5188840A (en) * 1985-09-26 1993-02-23 Chugai Seiyaku Kabushiki Kaisha Slow-release pharmaceutical agent
US5229164A (en) * 1985-12-19 1993-07-20 Capsoid Pharma Gmbh Process for producing individually dosed administration forms
US4863742A (en) * 1986-06-20 1989-09-05 Elan Corporation Plc Controlled absorption pharmaceutical composition
US4757090A (en) * 1986-07-14 1988-07-12 Mallinckrodt, Inc. Direct tableting acetaminophen compositions
US4762719A (en) * 1986-08-07 1988-08-09 Mark Forester Powder filled cough product
US4816262A (en) * 1986-08-28 1989-03-28 Universite De Montreal Controlled release tablet
US4820524A (en) * 1987-02-20 1989-04-11 Mcneilab, Inc. Gelatin coated caplets and process for making same
US4851226A (en) * 1987-11-16 1989-07-25 Mcneil Consumer Products Company Chewable medicament tablet containing means for taste masking
US4894236A (en) * 1988-01-12 1990-01-16 Choong-Gook Jang Direct compression tablet binders for acetaminophen
US5427814A (en) * 1988-02-03 1995-06-27 Nestec S.A. Process for protecting a fat against oxidation
US4929446A (en) * 1988-04-19 1990-05-29 American Cyanamid Company Unit dosage form
US5393533A (en) * 1988-09-09 1995-02-28 The Ronald T. Dodge Company Pharmaceuticals microencapsulated by vapor deposited polymers and method
US4906478A (en) * 1988-12-12 1990-03-06 Valentine Enterprises, Inc. Simethicone/calcium silicate composition
US4984240A (en) * 1988-12-22 1991-01-08 Codex Corporation Distributed switching architecture for communication module redundancy
US4960169A (en) * 1989-06-20 1990-10-02 Modien Manufacturing Co. Baffle for tubular heat exchanger header
US5146730A (en) * 1989-09-20 1992-09-15 Banner Gelatin Products Corp. Film-enrobed unitary-core medicament and the like
US5459983A (en) * 1989-09-20 1995-10-24 Banner Gelatin Products Corp. Tablet enrobing apparatus
US5213808A (en) * 1989-09-22 1993-05-25 Buhk Meditec A/A Controlled release article with pulsatile release
US5275822A (en) * 1989-10-19 1994-01-04 Valentine Enterprises, Inc. Defoaming composition
US5368863A (en) * 1990-01-24 1994-11-29 Alza Corporation Long-term delivery device with early startup
US5089270A (en) * 1990-05-15 1992-02-18 L. Perrigo Company Capsule-shaped tablet
US5213738A (en) * 1990-05-15 1993-05-25 L. Perrigo Company Method for making a capsule-shaped tablet
US5464631A (en) * 1990-06-27 1995-11-07 Warner-Lambert Company Encapsulated dosage forms
US5538125A (en) * 1990-11-05 1996-07-23 Mcneil-Ppc, Inc. Indexing and feeding systems for apparatus for gelatin coating tablets
US5436026A (en) * 1990-11-05 1995-07-25 Mcneil-Ppc, Inc. Discharge and transfer system for apparatus for gelatin coating tablets
US5228916A (en) * 1990-11-05 1993-07-20 Mcneil-Ppc, Inc. Apparatus for creating a gelatin coating
US5679406A (en) * 1990-11-05 1997-10-21 Mcneil-Ppc, Inc. Tablet dipping systems for apparatus for gelatin coating tablets
US5405642A (en) * 1991-02-27 1995-04-11 Janssen Pharmaceutica N.V. Method of highlighting intagliations in tablets
US5286497A (en) * 1991-05-20 1994-02-15 Carderm Capital L.P. Diltiazem formulation
US5489436A (en) * 1991-06-14 1996-02-06 Mcneil-Ppc, Inc. Taste mask coatings for preparation of chewable pharmaceutical tablets
US5912013A (en) * 1991-07-23 1999-06-15 Shire Laboratories, Inc. Advanced drug delivery system and method of treating psychiatric, neurological and other disorders with carbamazepine
US5200191A (en) * 1991-09-11 1993-04-06 Banner Gelatin Products Corp. Softgel manufacturing process
US5830501A (en) * 1991-12-06 1998-11-03 Alza Corporation Dosage form comprising hydrophilic polymer
US5609010A (en) * 1992-08-07 1997-03-11 Warner-Lambert Company Encapsulation method
US5795588A (en) * 1992-08-07 1998-08-18 Warner-Lambert Company Encapsulated product
US5511361A (en) * 1992-08-07 1996-04-30 Warner-Lambert Company Encapsulation method
US5738874A (en) * 1992-09-24 1998-04-14 Jagotec Ag Pharmaceutical tablet capable of liberating one or more drugs at different release rates
US5456920A (en) * 1993-02-10 1995-10-10 Takeda Chemical Industries, Ltd. Uncoated tablets and method of producing the same
US5391378A (en) * 1993-02-22 1995-02-21 Elizabeth-Hata International, Inc. Two-part medicinal tablet and method of manufacture
US5681584A (en) * 1993-04-23 1997-10-28 Ciba-Geigy Corporation Controlled release drug delivery device
US5415868A (en) * 1993-06-09 1995-05-16 L. Perrigo Company Caplets with gelatin cover and process for making same
US5469983A (en) * 1993-06-19 1995-11-28 Sado Yawata Heat insulating container and container holding member
US5641536A (en) * 1993-08-30 1997-06-24 Warner-Lambert Company Tablet coating method
US5871781A (en) * 1993-09-10 1999-02-16 Fuisz Technologies Ltd. Apparatus for making rapidly-dissolving dosage units
US5558829A (en) * 1994-03-04 1996-09-24 Mentor Corporation Method for providing a prosthesis with an injection port
US5464633A (en) * 1994-05-24 1995-11-07 Jagotec Ag Pharmaceutical tablets releasing the active substance after a definite period of time
US5711961A (en) * 1994-07-26 1998-01-27 Apr Applied Pharma Research S.A. Pharmaceutical compositions based on chewing gum and a method for the preparation thereof
US5830502A (en) * 1994-10-28 1998-11-03 Alza Corporation Injection-molded dosage form
US6117479A (en) * 1995-05-09 2000-09-12 Phoqus Limited Electrostatic coating
US5578336A (en) * 1995-06-07 1996-11-26 Monte; Woodrow C. Confection carrier for vitamins, enzymes, phytochemicals and ailmentary vegetable compositions and method of making
US5614207A (en) * 1995-06-30 1997-03-25 Mcneil-Ppc, Inc. Dry mouth lozenge
US5807579A (en) * 1995-11-16 1998-09-15 F.H. Faulding & Co. Limited Pseudoephedrine combination pharmaceutical compositions
US6294200B1 (en) * 1996-02-06 2001-09-25 Jagotec Ag Pharmaceutical tablet suitable to deliver the active substance in subsequent and predeterminable times
US5824338A (en) * 1996-08-19 1998-10-20 L. Perrigo Company Caplet and gelatin covering therefor
US5830801A (en) * 1997-01-02 1998-11-03 Motorola, Inc. Resistless methods of gate formation in MOS devices
US6103260A (en) * 1997-07-17 2000-08-15 Mcneil-Ppc, Inc. Simethicone/anhydrous calcium phosphate compositions
US6110499A (en) * 1997-07-24 2000-08-29 Alza Corporation Phenytoin therapy
US5942034A (en) * 1997-07-24 1999-08-24 Bayer Corporation Apparatus for the gelatin coating of medicaments
US6365185B1 (en) * 1998-03-26 2002-04-02 University Of Cincinnati Self-destructing, controlled release peroral drug delivery system
US6103257A (en) * 1998-07-17 2000-08-15 Num-Pop, Inc. System for delivering pharmaceuticals to the buccal mucosa
US6730646B1 (en) * 1998-07-29 2004-05-04 Reckitt Benckiser N.V. Composition for use in a dishwasher
US6200590B1 (en) * 1998-08-10 2001-03-13 Naphcare, Inc. Controlled, phased-release suppository and its method of production
US6350398B1 (en) * 1998-09-03 2002-02-26 Basf Aktiengesellschaft Process for producing coated solid dosage forms
US20010001280A1 (en) * 1998-09-09 2001-05-17 Liang-Chang Dong Dosage form comprising liquid formulation
US6270805B1 (en) * 1998-11-06 2001-08-07 Andrx Pharmaceuticals, Inc. Two pellet controlled release formulation for water soluble drugs which contains an alkaline metal stearate
US6248760B1 (en) * 1999-04-14 2001-06-19 Paul C Wilhelmsen Tablet giving rapid release of nicotine for transmucosal administration
US6555139B2 (en) * 1999-06-28 2003-04-29 Wockhardt Europe Limited Preparation of micron-size pharmaceutical particles by microfluidization
US20020051807A1 (en) * 2000-01-13 2002-05-02 Joaquina Faour Osmotic device containing alprazolam and an antipsychotic agent
US20020028240A1 (en) * 2000-04-17 2002-03-07 Toyohiro Sawada Timed-release compression-coated solid composition for oral administration
US20030068367A1 (en) * 2001-09-28 2003-04-10 Sowden Harry S. Systems, methods and apparatuses for manufacturing dosage forms
US20030072799A1 (en) * 2001-09-28 2003-04-17 Sowden Harry S. Systems, methods and apparatuses for manufacturing dosage forms
US20030086973A1 (en) * 2001-09-28 2003-05-08 Sowden Harry S Systems, methods and apparatuses for manufacturing dosage forms
US20030124183A1 (en) * 2001-09-28 2003-07-03 Sowden Harry S. Systems, methods and apparatuses for manufacturing dosage forms
US6742646B2 (en) * 2001-09-28 2004-06-01 Mcneil-Ppc, Inc. Systems, methods and apparatuses for manufacturing dosage forms

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10092521B2 (en) 2004-01-13 2018-10-09 Johnson & Johnson Consumer Inc. Rapidly disintegrating gelatinous coated tablets
US7879354B2 (en) 2004-01-13 2011-02-01 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
US8815290B2 (en) 2004-01-13 2014-08-26 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
US20110086098A1 (en) * 2004-01-13 2011-04-14 Rinker Roger A Rapidly disintegrating gelatinous coated tablets
US9149438B2 (en) 2004-01-13 2015-10-06 Johnson & Johnson Consumer Inc. Rapidly disintegrating gelatinous coated tablets
US11298324B2 (en) 2004-01-13 2022-04-12 Johnson & Johnson Consumer Inc. Rapidly disintegrating gelatinous coated tablets
US20050152970A1 (en) * 2004-01-13 2005-07-14 Rinker Roger A. Rapidly disintegrating gelatinous coated tablets
US10632078B2 (en) 2004-01-13 2020-04-28 Johnson & Johnson Consumer Inc. Rapidly disintegrating gelatinous coated tablets
US8067029B2 (en) 2004-01-13 2011-11-29 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
US20060093560A1 (en) * 2004-10-29 2006-05-04 Jen-Chi Chen Immediate release film coating
WO2006049564A1 (fr) * 2004-11-04 2006-05-11 Astrazeneca Ab Nouvelles formulations de pastilles a liberation modifiee pour inhibiteur de la pompe a protons
WO2006049565A1 (fr) * 2004-11-04 2006-05-11 Astrazeneca Ab Nouvelles formulations de comprimes a liberation modifiee pour inhibiteur de la pompe a protons
US20080003281A1 (en) * 2004-11-04 2008-01-03 Astrazeneca Ab Modified Release Tablet Formulations for Proton Pump Inhibitors
WO2007109713A2 (fr) * 2006-03-22 2007-09-27 Mcneil- Ppc, Inc. Formes posologiques ayant un revetement aleatoire
WO2007109713A3 (fr) * 2006-03-22 2008-01-17 Mcneil Ppc Inc Formes posologiques ayant un revetement aleatoire
US20070293587A1 (en) * 2006-05-23 2007-12-20 Haley Jeffrey T Combating sinus, throat, and blood infections with xylitol delivered in the mouth
AU2007268240B2 (en) * 2006-05-23 2012-12-06 Orahealth Corporation Xylitol troches and methods of use
US8865133B2 (en) * 2006-05-23 2014-10-21 Orahealth Corporation Bi-Layer Pressed Powders Oral Adhering Tablet with Acacia gum adhesive
US20070274927A1 (en) * 2006-05-23 2007-11-29 Jeffrey T. Haley Adherent polyol troche
US20100158974A1 (en) * 2006-10-19 2010-06-24 Schoemig Albert Coated implant
US20080300322A1 (en) * 2007-06-01 2008-12-04 Atlantic Pharmaceuticals, Inc. Delivery vehicles containing rosin resins
WO2009036999A1 (fr) * 2007-09-21 2009-03-26 N.V. Organon Système d'administration de médicament
US20090081278A1 (en) * 2007-09-21 2009-03-26 N.V. Organon Drug Delivery System
US8741329B2 (en) 2007-09-21 2014-06-03 Merck Sharp & Dohme B.V. Drug delivery system
GB2491327A (en) * 2010-03-05 2012-11-28 Univ Strathclyde Delayed prolonged drug delivery
US9283192B2 (en) * 2010-03-05 2016-03-15 University Of Strathclyde Delayed prolonged drug delivery
US9474719B2 (en) 2010-03-05 2016-10-25 University Of Strathclyde Pulsatile drug release
GB2491327B (en) * 2010-03-05 2017-05-10 Univ Strathclyde Delayed prolonged drug delivery
US20130022677A1 (en) * 2010-03-05 2013-01-24 University Of Strathclyde Delayed prolonged drug delivery
US10137091B2 (en) 2010-03-05 2018-11-27 University Of Strathclyde Immediate/delayed drug delivery
WO2011107750A3 (fr) * 2010-03-05 2012-05-03 University Of Strathclyde Administration retardée prolongée de médicament
US11065205B2 (en) 2010-03-05 2021-07-20 Drug Delivery International Limited Immediate/delayed drug delivery
US8486013B2 (en) * 2010-03-18 2013-07-16 Biotronik Ag Balloon catheter having coating
US20110230831A1 (en) * 2010-03-18 2011-09-22 Alexander Borck Balloon catheter having coating
US10413504B2 (en) 2013-12-11 2019-09-17 Merck Sharp & Dohme Corp. Intravaginal ring drug delivery system
US10596103B2 (en) 2013-12-11 2020-03-24 Merek Sharp & Dohme B.V. Drug delivery system for delivery of anti-virals
US11229577B2 (en) * 2016-09-09 2022-01-25 Merck Patent Gmbh Process for the manufacture of a solid pharmaceutical administration form

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