WO2000003696A1 - Enteric coated pharmaceutical tablet and method of manufacturing - Google Patents
Enteric coated pharmaceutical tablet and method of manufacturing Download PDFInfo
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- WO2000003696A1 WO2000003696A1 PCT/US1998/016323 US9816323W WO0003696A1 WO 2000003696 A1 WO2000003696 A1 WO 2000003696A1 US 9816323 W US9816323 W US 9816323W WO 0003696 A1 WO0003696 A1 WO 0003696A1
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- pharmaceutical composition
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- tablets
- coating
- medicament
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
Definitions
- the present invention is directed to an enteric-coated pharmaceutical composition in the form of a tablet which comprises an acid labile high drug load medicament, such as ddl, which is sensitive to a low pH environment of less than 3, and which includes an enteric coating such as Eudragit L-30-D 55 and a plasticizer, but which does not require a subcoat.
- the tablets have excellent resistance to disintegration at pH less than 3 but have excellent drug release properties at pH greater than 4.5.
- a novel method of making said pharmaceutical composition is also disclosed.
- Enteric coatings have been used for many years to arrest the release of the drug from orally ingestible dosage forms. Depending upon the composition and/or thickness, the enteric coatings are resistant to stomach acid for required periods of time before they begin to disintegrate and permit slow release of the drug in the lower stomach or upper part of the small intestines. Examples of some enteric coatings are disclosed in U.S. Patent No. 5,225,202 which is incorporated by reference fully herein. As set forth in U.S. Patent No.
- some examples of coating previously employed are beeswax and glyceryl monostearate; beeswax, shellac and cellulose; and cetyl alcohol, mastic and shellac, as well as shellac and stearic acid (U.S. Pat. No. 2,809,918); polyvinyl acetate and ethyl cellulose (U.S. Pat. No. 3,835,221); and neutral copolymer of polymethacrylic acid esters (Eudragit L30D) (F.W. Goodhart et al., Pharm. Tech., pp.
- enteric coating polymers begin to become soluble at pH 5.5 and above, with maximum solubility rates at pHs greater than 6.5.
- Numerous enteric coated and/or extended release pharmaceutical compositions and the methods of making these compositions have been disclosed in the art.
- Prior art compositions often comprise numerous extra ingredients in addition to the medicaments, such as fillers, buffering agents, binders and wetting agents, all of which add to the bulk of the composition and reduce the amount of active medicament which can be contained in the composition.
- the processes for preparing these aforementioned pharmaceutical compositions require multiple time consuming steps, including subcoating and outer coating steps.
- many of these pharmaceutical compositions are intended for delivery in the lower Gl tract, i.e. in the colon, as opposed to the upper intestines, i.e.
- U.S. Pat. No. 5,225,202 discloses enteric coated pharmaceutical compositions utilizing neutralized hydroxypropyl methylcellulose phthalate polymer (HPMCP) coating.
- the pharmaceutical compositions disclosed comprise an acid labile medicament core, a disintegrant, one or more buffering agents to provide added gastric protection in addition to the enteric coating, as well as the enteric coating and a plasticizer.
- the pharmaceutical composition may also include one or more lactose, sugar or starch fillers.
- an additional subcoat layer which acts as a physical barrier between the core and outer enteric coating layer is employed to prevent interaction of the acid labile drug and the acidic enteric coat.
- the HPMCP enteric coating starts its dissolution process at pH 5.0. The process of preparing this pharmaceutical composition requires numerous coating steps to apply the subcoat and then the enteric coat.
- 5,026,560 discloses a pharmaceutical composition and method of making said pharmaceutical composition, wherein the pharmaceutical composition comprises a Nonpareil seed core produced by coating sucrose with corn starch, spraying the core with an aqueous binder in a solution of water or ethanol and with a spraying powder containing a drug and low substituted hydroxypropylcellulose, followed by the application of an enteric coating.
- the pharmaceutical composition comprises a Nonpareil seed core produced by coating sucrose with corn starch, spraying the core with an aqueous binder in a solution of water or ethanol and with a spraying powder containing a drug and low substituted hydroxypropylcellulose, followed by the application of an enteric coating.
- U.S. Pat. No. 4,524,060 recites a slow release pharmaceutical composition which provides a sustained release composition for treating hypertensive patients, and which comprises a mixture of micronized indoramin or a pharmaceutically acceptable salt thereof, a water-channeling agent, a wetting agent, a disintegrant, the mixture being in the form of a non- compressed pellet and having an enteric coat or sustained release coat permeable to gastrointestinal juices.
- U.S. Pat. No. 5,536,507 is directed to a pharmaceutical composition having a delayed release coating or enteric coatings wherein the active agent in the composition is intended for release of a predominant amount of the drug at a point near the inlet to or within the large intestine and at a pH of approximately 6.4-7.0.
- compositions which include a medicament which is unstable in an acidic environment such as the stomach and which is not adequately buffered, will require an enteric protective coating to prevent release of such medicament prior to reaching the intestines.
- ddl also known as didanosine or 2',3'-dideoxyinosine, and marketed by Bristol-Myers Squibb Co. under the brand name Videx®
- Videx® is an acid labile drug which has the formula
- Videx® tablets also contain aspartame, sorbitol, microcrystalline cellulose, Polyplasdone®, mandarin-orange flavor, and magnesium stearate.
- Videx® Buffered Powder for Oral Solution is supplied for oral administration in single-dose packets containing 100, 167 or 250 mg of didanosine. Packets of each product strength also contain a citrate- phosphate buffer (composed of dibasic sodium phosphate, sodium citrate, and citric acid) and sucrose.
- a Videx® Pediatric Powder for Oral Solution is also available and which is supplied for oral administration in 4- or 8-ounce glass bottles containing 2 or 4 grams of didanosine respectively, and is to be mixed with commercial antacid before oral ingestion.
- the current chewable/dispersible buffered tablets are not conducive from a patient ease of use standpoint.
- the other products which are a part of the AIDS therapeutic cocktail are capsules or tablets and easily swallowed, the Videx® (referred to herein as "ddl”) Chewable/Dispersible Buffered Tablets must be thoroughly chewed, manually crushed, or uniformly dispersed in water before administration. Because ddl degrades rapidly at acidic pH, ddl, in its chewable/dispersible form and its buffered powder for oral solution, contains buffering agents and is administered with antacids in the pediatric powder form.
- a tablet comprising a medicament core and having a coating which prevents release of the medicament in the stomach and allows for release of the drug in the small intestine thereby eliminating the need for an antacid which may cause Gl imbalance upon chronic use.
- pharmaceutical compositions which include a medicament which is unstable in an acid environment such as the stomach will require such a protective coating to prevent release of such medicament prior to reaching the intestines.
- an enteric coated, high drug load pharmaceutical composition and a method of making said pharmaceutical composition, is provided which includes a medicament which may degrade in a low pH environment but which is protected from doing so by the enteric coating.
- the pharmaceutical composition of the invention which is advantageously in the form of tablets, includes a core which comprises a medicament, such as ddl, which is sensitive to a low pH environment and optionally a binder or filler, a disintegrant or swelling agent, and a lubricant.
- the core further comprises an enteric coating surrounding the core which includes a methacrylic acid copolymer and a plasticizer.
- novel enteric coated pharmaceutical of the invention will provide for protection of the medicament or therapeutically active agent, such as ddl, at pH's less than 3 (such as found in the stomach) but will permit drug release at a pH of 4.5 or higher (such as found in the upper intestines).
- the medicament or therapeutically active agent such as ddl
- the pharmaceutical composition of the invention will usually include drugs which are chemically unstable in acidic environments.
- the pharmaceutical composition of the invention provides excellent protection in very acidic environments (pH ⁇ 3) while not delaying the rapid release in regions of pH greater than 4, whether this be the upper intestine or the duodenum.
- Most of the enteric coating materials known in the art are acidic in nature and hence may cause chemical instability when in contact with acid labile ingredients. This is especially true under high temperature and humid conditions experienced during an aqueous coating process.
- a protective coat or subcoat is usually applied between the particles, beadlets, pellets, tablets, etc., and the enteric coat.
- This protective coat physically separates the acid labile drug from the acidic enteric coat, and hence improves stability of the formulation.
- the process of applying such a subcoat often entails multiple burdensome and time-consuming steps. Furthermore, the subcoat can cause a delay in drug release.
- a process is thus described by which tablets, beadlets, pellets, and/or particles containing acid labile drugs can be successfully aqueous enteric coated without application of the protective coat or subcoat.
- This process involves raising the pH of the enteric coating suspension solution by using alkalizing agents. The pH of the coating suspension is raised below the point where enteric integrity of the polymer could be lost.
- the process may also involve the inclusion of binders, such as sodium carboxymethylcellulose, fillers, such as microcrystalline cellulose, disintegrants, such as sodium starch glycolate, and other excipients, such as magnesium oxide, which are relatively alkaline in nature, in the formulations of cores intended for enteric coating. Raising the pH of the coating suspension provides a more stable composition for the acid labile drug in the core.
- the process of the present invention illustrates the preparation of high (up to 99.5%) potency (uncoated) tablets, for acid labile drugs, such as ddl, using an aqueous process. No specialized equipment is required as conventional blending, compacting, tableting, and coating equipment was found to be adequate for tablet formation and coating.
- the coated tablets pass through the stomach first.
- the transit time for the stomach is approximately two hours and the pH of this region is approximately 1 to 3.
- the enteric coating component allows the medicament core to remain substantially intact and thus prevents the pharmacologically active substance from being released in this region or the acid from penetrating through to the tablet core.
- the tablets then pass through the small intestine wherein the majority of the enteric coating component will dissolve and release the pharmacologically active substance therein.
- the small intestine consists of the duodenum, jejunum and ileum. Transit time through the small intestine is approximately 2-4 hours and the pH of these regions is approximately 5 to approximately 7.2.
- enteric coating is a polymer material or materials which encase the medicament core.
- the polymeric enteric coating material in the present invention does not contain any active compound, i.e. any therapeutically active agent, of the present invention.
- a substantial amount or all of the enteric polymer coating material is dissolved before the medicament or therapeutically active agent is released from the dosage form, so as to achieve delayed dissolution of the medicament core.
- a suitable pH-sensitive polymer is one which will dissolve in intestinal juices at the higher pH levels (pH greater than 4.5), such as within the small intestine and therefore permit release of the pharmacologically active substance in the regions of the small intestine and not in the upper portion of the Gl tract, such as the stomach.
- the polymer coating material is selected such that the therapeutically active agent will be released when the dosage form reaches the small intestine or a region in which the pH is greater than pH 4.5.
- Preferred coating pH-sensitive materials which remain intact in the lower pH environs of the stomach, but which disintegrate or dissolve at the pH commonly found in the small intestine of the patient.
- the enteric polymer coating material begins to dissolve in an aqueous solution at pH between about 4.5 to about 5.5.
- the pH-solubility behavior of the enteric polymers of the present invention are such that significant dissolution of the enteric polymer coating will not occur until the dosage form has emptied from the stomach.
- the pH of the small intestine gradually increases from about 4.5 to about 6.5 in the duodenal bulb to about 7.2 in the distal portions of the small intestine (ileum).
- the coating In order to provide predictable dissolution corresponding to the small intestine transit time of about 3 hours and permit reproducible release therein, the coating should begin to dissolve within the pH range of the duodenum and continue to dissolve at the pH range within the small intestine. Therefore, the amount of enteric polymer coating should be such that it is substantially dissolved during the approximate three hour transit time within the small intestine.
- the pharmaceutical medicament present in the core will be an acid labile drug such as ddl, pravastatin, erythromycin, digoxin, pancreatin, ddA, ddC, and the like.
- the present invention is not limited to these drugs and other drugs may be used as well.
- the invention is particularly adapted to pharmaceutical compositions, such as tablets, which contain ddl as the medicament, ddl will be present in an amount of about up to about 95% of the composition in the coated tablets.
- binders or fillers may be present in the core.
- Microcrystalline cellulose (PH-101) is the preferred binder most suitable for use herein.
- examples of other binders which may be used include sodium carboxymethylcellulose AvicelTM PH101 , AvicelTM RC 591 , AvicelTM CL-611 , (FMC Corp), CeolusTM (FMC Corp.), ProSolvTM (Edward Mendell Co.) MethocelTM E-5 (Dow Corp.), Starch 1500 (Colorcon, Ltd.), Hydroxypropyl Methylcellulose (HPMC) (Shin-Etsu Chemical Co., Ltd.), Polyvinylpyrrolidone, Potassium Alginate and Sodium Alginate.
- the core of the composition of the invention may also include one or more disintegrants or swelling agents, such as sodium starch glycolate marketed under the trademark EXPLOTAB (Edward Mendell Co.), Ac-Di-Sol (cross-linked sodium carboxymethylcellulose) (FMC Corp), croscarmellose sodium, corn starch, or cross linked polyvinylpyrrolidone.
- a lubricant such as magnesium stearate, may also be used in the preparation of the uncoated tablet, specifically as a lubricant for the compaction and tableting process.
- the core employed in the pharmaceutical composition of the invention will be formed of a tablet, preferably a round, biconvex tablet, approximately 3/16 of an inch.
- the invention is not, however, limited in the size of the tablet and tablets of varying sizes may be made. Smaller sized tablets are advantageous, however, since they pass through the stomach with more ease than larger sized tablets.
- the tablet of the present invention having core comprising ddl as the medicament has the same bioavailability as the beadlet disclosed in co-pending U.S. Application No. 09/083,597, which was filed on May 22, 1998.
- the core can be prepared from a wet granulation process, using any of the wet granulation binders (if necessary) commonly used in the art, such as pregelatinized starch, polyvinylpyrrolidone, HPMC sodium carboxymethycellulose, potassium or sodium alginate.
- the wet granulation process comprises the steps of preparing granules suitable for tableting by blending a mixture comprising the medicament, a binder, and optionally, a disintegrant and filler; adding a predetermined amount of water or granulation solvent to form a wet mass blend; sizing the wet mass blend into granules to aid drying; drying the wet granules to remove excess moisture; sizing the dried granules into granules suitable for tableting, and adding lubricant, one or more fillers, one or more dry binders, optionally a disintegrant, and other excipients necessary for tableting the granules.
- the enteric coating according to the present invention will include methacrylic acid copolymer, a plasticizer, and a sufficient quantity of NaOH to adjust the pH of the suspension.
- Other alkalizing agents such as potassium hydroxide, calcium carbonate, sodium carboxymethylcellulose, magnesium oxide, and magnesium hydroxide can also be used.
- Eudragit L-30-D 55 is an aqueous acrylic resin dispersion, an anionic copolymer derived from methacrylic acid and ethyl acrylate with a ratio of free carboxyl groups to the ester of approximately 1 :1 , and a mean molecular weight of approximately 250,000, is supplied as an aqueous dispersion containing 30% w/w of dry lacquer substance, and is marketed by Rohm-Pharma Co., Germany.
- As an aqueous-based coating no dangerous or environmentally harmful organic solvents are utilized.
- Eudragit L-30-D-55 is the preferred coating polymer
- the invention is not limited in this respect and other enteric coating polymers known in the art, such as hydroxypropyl methylcellulose phthalate HP50 (HPMCP-HP50) (USP/NF 220824), HP55 (HPMCP-HP55)(USP/NF type 200731) and HP55S available from Shin Etsu Chemical, CoatericTM (polyvinyl acetate phthalate) (Colorcon Ltd.), SuretericTM (polyvinyl acetate phthalate)(Colorcon, Ltd.), or AquatericTM (cellulose acetate phthalate)(FMC Corp.), and the like may be employed
- the enteric coating will also preferably contain a plasticizer which is preferably diethyl phthalate, although the invention is not limited in this respect and other plasticizers may be used such as triethyl citrate (Citroflex- 2), triacetin, tributyl sebecate, or polyethylene glycol.
- a plasticizer which is preferably diethyl phthalate, although the invention is not limited in this respect and other plasticizers may be used such as triethyl citrate (Citroflex- 2), triacetin, tributyl sebecate, or polyethylene glycol.
- the enteric coating employed in the present invention is substantially easier to process than previously reported coating systems, and is especially advantageous for coating small diameter, low mass particles (tablets) with minimal processing problems (sticking/picking) without the need for organic solvents.
- a subcoat layer which may be comprised of one or more film-formers or plasticizers, and which acts as a physical barrier between the core and the outer enteric coating layer will be employed.
- the novel pharmaceutical composition of the present invention does not require a subcoat since the need for such an insulating layer is eliminated by raising the pH of the aqueous coating suspension. Since the coating is designed to breakdown at pH 5.5, the enteric coating applied at pH 5 permits relatively rapid breakdown in the intestine as only a small amount of additional alkalinity is required to bring the pH to 5.5.
- a preferred formulation for the preparation of an enteric film coating suspension to coat the uncoated 50 mg tablets is set out below.
- the enteric coated pharmaceutical composition in the form of tablets may be prepared by a process which comprises the steps of mixing an acid labile medicament, a binder/filler, such as microcrystalline cellulose, a disintegrant, such as sodium starch glycolate, and a first portion of a lubricant, such as magnesium stearate, for compaction, in a tumbling type blender, to prepare a dry blend.
- a lubricant such as magnesium stearate
- the enteric coated pharmaceutical composition in the form of tablets may be prepared by a process which comprises the steps of mixing an acid labile medicament, a binder/filler, such as microcrystalline cellulose, a disintegrant, such as sodium starch glycolate, and a first portion of a lubricant, such as magnesium stearate, for compaction, in a tumbling type blender, to prepare a dry blend.
- the blend is then screened and placed back in the blender for a second blending.
- the resulting blend is slugged or compacte
- the pH could be adjusted up to 5.4 as may be necessary of a specific formulation.
- a top spray mode fluid bed apparatus is preferred, the invention is not limited in this respect, and any suitable spray coating means, including one with a bottom spray, or a pan type coater, may also be utilized.
- the tablets may be ingested individually or, in another embodiment of the invention, may be filled into dissolvable, hard shell capsules, such as gelatin capsules of varying sizes depending on the dosage of medicament desired. If the tablets are to be encapsulated, a hydrophobic anti-adherent, such as talc, is added (range 0.1 to 4% by weight) to the film coated tablets and blended.
- a hydrophobic anti-adherent such as talc
- EXAMPLE 1 A ddl formulation for 50mg tablets having the following composition was prepared as described below.
- ddl tablets The preparation of ddl tablets was commenced by adding ddl, microcrystalline cellulose, sodium starch glycolate and a first portion of magnesium stearate for compaction, into a tumbling type blender .
- the ingredients were blended for 10 ⁇ 2 minutes. Prior to blending, any of the initial ingredients which were lumpy, were passed through a #20 mesh screen.
- the blended mixture was then passed through a #40 size mesh screen and re-placed into the tumbling type blender and blended again for 10 ⁇ 2 minutes.
- the resulting blend was then slugged using a 3/4" flat face punches. The slugs were then passed through #10 and #20 size mesh screens for sizing.
- a second portion of magnesium stearate needed for tableting was then calculated and placed into the tumbling type blender with the granulation prepared for the sizing of the slugs and blended for 10 ⁇ 2 minutes.
- the resulting blend was then tableted to obtain the desired tablet weight and hardness.
- Eudragit L-30-D 55 was filtered through a #60 mesh screen to remove any lumps present therein.
- the filtered Eudragit was weighed and then added with stirring to a tarred vessel containing one-half the amount of water required. The mixture was continuously stirred for 5 minutes or until a uniform mixture was visually evident. With continuous stirring, diethyl phthalate was added to the vessel and stirring continued for 20 minutes or until a uniform mixture was visually evident. A pH meter was then standardized using pH 4 and pH 7 buffers. With continued stirring, a NaOH solution was added to the vessel until a pH of 5.0 ⁇ 0.1 was obtained. The formula weight of the coating suspension was adjusted using water and stirring was continued for an additional 10 minutes.
- the tablet coating procedure utilized a fluid bed apparatus with a top spray mode and appropriate distribution plate to allow fluidization of the product (tablet) in the center.
- the tablets were pre-warmed in the coating unit to a temperature between 45 -50 °C. An inlet temperature of 50 ⁇ 2 °C was determined to be adequate. The spray rate was adjusted to allow uniform coating and adequate drying of the coat. An 8 ⁇ 0.5% weight gain due to the film coat was determined to be sufficient. After coating, the tablets were dried for approximately 10 minutes at an inlet temperature of approximately 50 °C.
- the so formed enteric coated ddl product was found to give excellent protection against gastric acid (at pH of 3) but had excellent release of ddl at pH's above 5.
- EXAMPLE 2 A preferred 50 mg ddl formulation in the form of enteric coated tablets was prepared as described below, ddl (50.00 mg), microcrystalline cellulose (17.00 mg) sodium starch glycolate (2.10 mg) and a first portion of magnesium stearate for compaction (0.60 mg) were placed into a suitable tumbling type blender and blended for 10 ⁇ 2 min. Prior to blending, if any of the ingredients required delumping, they were passed through a #20 mesh screen.
- the blended mixture was then passed through a #40 size mesh screen and re-placed into the tumbling type blender and blended again for 10 ⁇ 2 minutes.
- the resulting blend was then slugged using a 3/4" flat face punches to obtain slugs with a weight and hardness of 1 ⁇ 0.2 g and 15 - 20 SCU, respectively.
- the slugs were then passed through #10 and #20 size mesh screens.
- a second portion of magnesium stearate (0.3 g) for tableting was then placed into the tumbling type blender with the slugs and blended for 10 ⁇ 2 minutes.
- the resulting blend was then tableted using 3/16" round, plain, deep concave punches to the desired weight at a tablet hardness of 3-6 SCU.
- a quantity of film coating suspension in an amount (g) per 100 g for coating the 50 mg ddl tablets was commenced by adding approximately 50 g of water into a suitable container having a stirring mechanism. While the water was being stirred moderately, 33.33 g Eudragit L 30 D-55 was slowly added thereto. Before adding to the water, the Eudragit L 30 D-55 was screened through a #60 size mesh screen. With continued stirring, 1.50 g diethyl phthalate was added to the water/Eudragit mixture until the diethyl phthalate was in complete solution. While stirring, a sufficient quantity of sodium hydroxide solution (0.1 to 1 N) was slowly added in order to adjust the pH of the suspension to 5.0. With continued stirring, water was added to make the formula weight, and the suspension was stirred for an additional 10 minutes.
- the tablet coating procedure utilized an Aeromatic Table-top (STREA-1) fluid bed apparatus, with top spray mode and appropriate distribution plate to allow fluidization of the product (tablet) in the center.
- the coating conditions utilized in the process were:
- the tablets were pre-warmed in the coating unit to a temperature between 45 - 50 °C. An inlet temperature of 50 ⁇ 2 °C was determined to be adequate. The spray rate was adjusted to allow uniform coating and adequate drying of the coat. An 8 ⁇ 0.5% weight gain due to the film coat was determined to be sufficient. After coating, the tablets were dried for approximately 10 minutes at an inlet temperature of approximately 50 °C.
- the so formed enteric coated ddl product was found to provide excellent protection against gastric acid (at pH of 3) but had excellent release of ddl at pH's above 5.
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Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
UA2001021131A UA73092C2 (en) | 1998-07-17 | 1998-06-08 | Tablets with enteric coating and method for their manufacture |
NZ508298A NZ508298A (en) | 1998-07-17 | 1998-08-06 | Enteric coated acid labile medicament |
IL13970198A IL139701A0 (en) | 1998-07-17 | 1998-08-06 | Enteric coated pharmaceutical tablet and method of manufacturing |
SK1883-2000A SK285152B6 (en) | 1998-07-17 | 1998-08-06 | Enteric coated pharmaceutical composition a method for its preparation |
EEP200100033A EE05021B1 (en) | 1998-07-17 | 1998-08-06 | Enteric-coated pharmaceutical composition and method for its preparation |
EP98940790A EP1098635B1 (en) | 1998-07-17 | 1998-08-06 | Enteric coated pharmaceutical tablet containing didanosine |
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DE69824319T DE69824319T2 (en) | 1998-07-17 | 1998-08-06 | DIDANOSINE TABLETS WITH A MAGENTAL-FIRESISTIC COAT |
AT98940790T ATE268165T1 (en) | 1998-07-17 | 1998-08-06 | DIDANOSIN TABLETS WITH ENTERIC JUICE RESISTANT COATING |
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Families Citing this family (112)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US8088060B2 (en) | 2000-03-15 | 2012-01-03 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
US6555581B1 (en) | 2001-02-15 | 2003-04-29 | Jones Pharma, Inc. | Levothyroxine compositions and methods |
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US20030165564A1 (en) * | 2001-10-29 | 2003-09-04 | Franz G. Andrew | Levothyroxine compositions having unique triiodothyronine Tmax properties |
WO2003049693A2 (en) * | 2001-12-06 | 2003-06-19 | Wyeth | Method and composition for inducing weight loss |
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US8323692B2 (en) | 2002-02-21 | 2012-12-04 | Valeant International Bermuda | Controlled release dosage forms |
ES2377729T3 (en) * | 2002-02-21 | 2012-03-30 | Valeant International (Barbados) Srl | Modified release formulations of at least one form of tramadol |
US6982080B2 (en) * | 2002-03-15 | 2006-01-03 | Wyeth | Hydroxyethyl starch—containing polypeptide compositions |
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CA2500663C (en) | 2002-10-01 | 2013-05-28 | Banner Pharmacaps, Inc. | Enteric composition for the manufacture of soft capsule wall |
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US8168228B2 (en) * | 2003-10-17 | 2012-05-01 | Sandoz Ag | Antibiotic clarithromycin micropellet compositions |
US20050084540A1 (en) * | 2003-10-17 | 2005-04-21 | Indranil Nandi | Taste masking antibiotic composition |
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WO2005074598A2 (en) | 2004-01-30 | 2005-08-18 | Johns Hopkins University | Nitroxyl progenitor compounds and methods of use |
RU2375047C2 (en) * | 2004-03-26 | 2009-12-10 | Лек Фармасьютиклз Д.Д. | Pharmaceutical medicinal form, resistant to gastric juice activity, which includes n-(2-(2-phthalimidoetoxy)acetyl)-l-alanyl-d-glutamic acid (lk 423) |
US20050281876A1 (en) * | 2004-06-18 | 2005-12-22 | Shun-Por Li | Solid dosage form for acid-labile active ingredient |
US8980930B2 (en) | 2004-06-25 | 2015-03-17 | The Johns Hopkins University | Angiogenesis inhibitors |
WO2006012536A2 (en) | 2004-07-22 | 2006-02-02 | Ritter Andrew J | Methods and compositions for treating lactose intolerance |
EP1958625A1 (en) * | 2004-11-18 | 2008-08-20 | Brystol-Myers Squibb Company | Enteric coate bead comprising ixabepilone and preparation thereof |
WO2006054175A2 (en) * | 2004-11-18 | 2006-05-26 | Aurobindo Pharma Limited | Stable dosage forms of acid labile drug |
WO2006055742A1 (en) * | 2004-11-18 | 2006-05-26 | Bristol-Myers Squibb Company | Enteric coated bead comprising epothilone or epothilone analog, and preparation and administration thereof |
US20060280789A1 (en) * | 2004-12-27 | 2006-12-14 | Eisai Research Institute | Sustained release formulations |
US20060246003A1 (en) * | 2004-12-27 | 2006-11-02 | Eisai Co. Ltd. | Composition containing anti-dementia drug |
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US20110223248A1 (en) * | 2007-12-12 | 2011-09-15 | Ritter Pharmaceuticals, Inc. | Methods and compositions for treating lactose intolerance |
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US8632805B2 (en) * | 2008-06-20 | 2014-01-21 | Mutual Pharmaceutical Company, Inc. | Controlled-release formulations, method of manufacture, and use thereof |
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US8729097B2 (en) | 2008-10-06 | 2014-05-20 | The Johns Hopkins University | Quinoline compounds as inhibitors of angiogenesis, human methionine aminopeptidase, and SIRT1, and methods of treating disorders |
CA2752800C (en) | 2009-02-24 | 2017-12-05 | Ritter Pharmaceuticals, Inc. | Prebiotic formulations and methods of use |
EP2405898A2 (en) | 2009-03-09 | 2012-01-18 | Council Of Scientific & Industrial Research | Sustained release composition of therapeutic agent |
SI2407166T1 (en) * | 2009-03-13 | 2013-12-31 | Toyama Chemical Co., Ltd. | Tablet and granulated powder containing 6-fluoro-3-hydroxy-2-pyrazinecarboxamide |
US20110160200A1 (en) * | 2009-11-23 | 2011-06-30 | Cardioxyl Pharmaceuticals, Inc. | Nitroxyl Progenitors for the Treatment of Pulmonary Hypertension |
CA2782110A1 (en) * | 2009-12-07 | 2011-06-16 | Johns Hopkins University | N-acyloxysulfonamide and n-hydroxy-n-acylsulfonamide derivatives |
EP2509942A2 (en) | 2009-12-07 | 2012-10-17 | Johns Hopkins University | Bis-acylated hydroxylamine derivatives |
EP3202406A1 (en) | 2010-04-28 | 2017-08-09 | Ritter Pharmaceuticals, Inc. | Prebiotic formulations and methods of use |
ES2610226T3 (en) | 2010-10-08 | 2017-04-26 | Xcovery Holding Company Llc | 6-Amino-pyridazin-3-yl-carboxamide compounds substituted as protein kinase modulators |
WO2013049731A1 (en) * | 2011-09-30 | 2013-04-04 | Stomavite Llc | A supplement for ostomy patients |
JP6177246B2 (en) | 2011-10-17 | 2017-08-09 | ザ・ジョンズ・ホプキンス・ユニバーシティ | Meldrum acid, barbituric acid, and pyrazolone derivatives as HNO donors substituted with hydroxylamine |
CN102357088A (en) * | 2011-10-26 | 2012-02-22 | 河北山姆士药业有限公司 | Metformin hydrochloride enteric-coated tablet |
CN102526746B (en) * | 2012-02-04 | 2013-09-18 | 安徽山河药用辅料股份有限公司 | Preparation method of enteric type aqueous dispersion coating material |
WO2014070919A1 (en) | 2012-11-01 | 2014-05-08 | The Johns Hopkins University | Controlled hno release through intramolecular cyclization-elimination |
US20140141075A1 (en) | 2012-11-21 | 2014-05-22 | Warner Chilcott Company, Llc | 5-aminosalicylic acid capsule formulation |
HUE041861T2 (en) | 2013-01-18 | 2019-06-28 | Cardioxyl Pharmaceuticals Inc | Pharmaceutical compositions comprising nitroxyl donors |
AU2014251207B2 (en) | 2013-04-07 | 2019-06-13 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for personalized neoplasia vaccines |
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WO2015077717A1 (en) | 2013-11-25 | 2015-05-28 | The Broad Institute Inc. | Compositions and methods for diagnosing, evaluating and treating cancer by means of the dna methylation status |
US11725237B2 (en) | 2013-12-05 | 2023-08-15 | The Broad Institute Inc. | Polymorphic gene typing and somatic change detection using sequencing data |
JP7060324B2 (en) | 2013-12-20 | 2022-04-26 | ザ・ブロード・インスティテュート・インコーポレイテッド | Combination therapy with neoantigen vaccine |
WO2015109210A1 (en) | 2014-01-17 | 2015-07-23 | Cardioxyl Pharmaceuticals, Inc. | N-hydroxymethanesulfonamide nitroxyl donors |
WO2015153841A1 (en) | 2014-04-04 | 2015-10-08 | Ritter Pharmaceuticals, Inc. | Methods and compositions for microbiome alteration |
ES2749682T3 (en) | 2014-05-27 | 2020-03-23 | Cardioxyl Pharmaceuticals Inc | Pyrazolone derivatives as nitroxyl donors |
WO2015183838A1 (en) | 2014-05-27 | 2015-12-03 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives as nitroxyl donors |
US9464061B2 (en) | 2014-05-27 | 2016-10-11 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives |
CA2950203C (en) | 2014-06-20 | 2019-09-03 | Banner Life Sciences Llc | Enteric soft capsule compositions |
US10975442B2 (en) | 2014-12-19 | 2021-04-13 | Massachusetts Institute Of Technology | Molecular biomarkers for cancer immunotherapy |
US10993997B2 (en) | 2014-12-19 | 2021-05-04 | The Broad Institute, Inc. | Methods for profiling the t cell repertoire |
CA2970958A1 (en) | 2014-12-23 | 2016-06-30 | Cerecor, Inc. | Compounds, compositions and methods |
RU2668499C2 (en) * | 2015-03-12 | 2018-10-01 | Закрытое Акционерное Общество "Фармфирма "Сотекс" | Pharmaceutical composition in form of tablets with enteric coating and method of preparation thereof |
TW202346325A (en) | 2015-05-20 | 2023-12-01 | 美商博德研究所有限公司 | Shared gata3-related tumor-specific neoantigens |
EP3307251B8 (en) | 2015-06-09 | 2021-12-01 | Ocuphire Pharma, Inc. | Fluorocyclopentenylcytosine uses and processes of preparation |
CN108025009A (en) | 2015-09-04 | 2018-05-11 | 瑞恩药品公司 | The application method of quinoxalinyl-piperazine amide |
IL298281A (en) | 2015-11-03 | 2023-01-01 | Brigham & Womens Hospital Inc | Therapeutic microbiota for the treatment and/or prevention of food allergy |
US10537528B2 (en) | 2015-11-16 | 2020-01-21 | The Regents Of The University Of California | Methods of treating non-alcoholic steatohepatitis (NASH) using cysteamine compounds |
US10143665B2 (en) | 2015-11-17 | 2018-12-04 | Horizon Orphan Llc | Methods for storing cysteamine formulations and related methods of treatment |
AU2017254477A1 (en) | 2016-04-18 | 2018-11-01 | Jennifer G. ABELIN | Improved HLA epitope prediction |
CN108366994B (en) | 2016-10-03 | 2021-10-01 | 杭州高光制药有限公司 | Novel selective inhibitors of Jak1 and uses thereof |
EP3574116A1 (en) | 2017-01-24 | 2019-12-04 | The Broad Institute, Inc. | Compositions and methods for detecting a mutant variant of a polynucleotide |
CA3088630A1 (en) | 2017-12-15 | 2019-06-20 | Solarea Bio, Inc. | Microbial compositions and methods for treating type 2 diabetes, obesity, and metabolic syndrome |
JP2021522308A (en) | 2018-05-04 | 2021-08-30 | トゥリーズ | TLR3 ligand that activates both epithelial and bone marrow cells |
FR3083545A1 (en) | 2018-07-04 | 2020-01-10 | Institut National De La Recherche Agronomique | USE OF A ROSEBURIA INTESTINALIS STRAIN FOR THE PREVENTION AND TREATMENT OF INTESTINAL INFLAMMATION |
EP3846830A4 (en) | 2018-09-05 | 2022-07-06 | Solarea Bio, Inc. | Methods and compositions for treating musculoskeletal diseases |
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WO2020072700A1 (en) | 2018-10-02 | 2020-04-09 | Dana-Farber Cancer Institute, Inc. | Hla single allele lines |
CN117562174A (en) | 2018-11-05 | 2024-02-20 | 奇迹生物公司 | Microbial compositions comprising ellagitannins and methods of use |
US20220062394A1 (en) | 2018-12-17 | 2022-03-03 | The Broad Institute, Inc. | Methods for identifying neoantigens |
US20220202818A1 (en) | 2019-04-18 | 2022-06-30 | The Regents Of The University Of Michigan | Combination with checkpoint inhibitors to treat cancer |
EP3986163A2 (en) | 2019-06-19 | 2022-04-27 | Solarea Bio, Inc. | Microbial compositions and methods for producing upgraded probiotic assemblages |
KR20210043779A (en) * | 2019-10-11 | 2021-04-22 | 넨시스(주) | Manufacturing method of pancreatin enteric coated pellet |
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CN116249774A (en) | 2020-05-26 | 2023-06-09 | 迪奥尼斯治疗公司 | Nucleic acid artificial mini proteome library |
WO2021248093A1 (en) | 2020-06-05 | 2021-12-09 | Henry Ford Health System | Daclatasvir for use in treating lung and prostate cancer |
EP4267554A1 (en) | 2020-12-22 | 2023-11-01 | Mekanistic Therapeutics LLC | Substituted aminobenzyl heteroaryl compounds as egfr and/or pi3k inhibitors |
WO2022189861A1 (en) | 2021-03-08 | 2022-09-15 | Tollys | Carbohydrate conjugates of tlr3 ligands and uses thereof |
EP4385510A1 (en) | 2021-08-10 | 2024-06-19 | Betta Pharmaceuticals Co., Ltd | Use of ensartinib or salt thereof in treatment of disease carrying met 14 exon skipping mutation |
WO2023076733A1 (en) | 2021-11-01 | 2023-05-04 | Dana-Farber Cancer Institute, Inc. | Biologically selected nucleic acid artificial mini-proteome libraries |
WO2023092150A1 (en) | 2021-11-22 | 2023-05-25 | Solarea Bio, Inc. | Methods and compositions for treating musculoskeletal diseases, treating inflammation, and managing symptoms of menopause |
US20230190834A1 (en) | 2021-12-21 | 2023-06-22 | Solarea Bio, Inc. | Immunomodulatory compositions comprising microbial entities |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5326570A (en) * | 1991-07-23 | 1994-07-05 | Pharmavene, Inc. | Advanced drug delivery system and method of treating psychiatric, neurological and other disorders with carbamazepine |
US5422121A (en) * | 1990-11-14 | 1995-06-06 | Rohm Gmbh | Oral dosage unit form |
US5510114A (en) * | 1993-05-18 | 1996-04-23 | Instituto Biochimico Italiano Giovanni Lorenzini S.P.A. | Slow release pharmaceutical composition containing a bile acid as an active ingredient |
US5556839A (en) * | 1991-04-29 | 1996-09-17 | Eli Lilly And Company | Form II Dirithromycin |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2809918A (en) | 1955-10-17 | 1957-10-15 | Victor M Hermelin | Sustained release pharmaceutical preparations |
DE2010416B2 (en) | 1970-03-05 | 1979-03-29 | Hoechst Ag, 6000 Frankfurt | Orally applicable dosage form with sustained release effect |
FR2471186A1 (en) | 1979-12-10 | 1981-06-19 | Roussel Uclaf | NEW COLIC DELITESCENCE TABLETS AND THEIR PREPARATION PROCESS |
US4432996A (en) | 1980-11-17 | 1984-02-21 | Merck & Co., Inc. | Hypocholesterolemic fermentation products and process of preparation |
ZA822995B (en) | 1981-05-21 | 1983-12-28 | Wyeth John & Brother Ltd | Slow release pharmaceutical composition |
US4556552A (en) | 1983-09-19 | 1985-12-03 | Colorcon, Inc. | Enteric film-coating compositions |
US4704295A (en) | 1983-09-19 | 1987-11-03 | Colorcon, Inc. | Enteric film-coating compositions |
US4728512A (en) | 1985-05-06 | 1988-03-01 | American Home Products Corporation | Formulations providing three distinct releases |
GB8512330D0 (en) | 1985-05-15 | 1985-06-19 | Wellcome Found | Antiviral compounds |
JPS62501712A (en) | 1985-08-26 | 1987-07-09 | アメリカ合衆国 | Anti-HTLV-3/LAV agent containing 2',3'-dideoxyinosine, 2',3'-dideoxyguanosine or 2',3'-dideoxyadenosine |
US5254539A (en) | 1985-08-26 | 1993-10-19 | U.S. Government, Dept. Of Health And Human Services, C/O National Institutes Of Health | Method of treating HIV with 2',3'-dideoxyinosine |
US4975283A (en) | 1985-12-12 | 1990-12-04 | Bristol-Myers Squibb Company | Stabilized enteric coated aspirin granules and process for preparation |
US4775536A (en) | 1986-02-24 | 1988-10-04 | Bristol-Myers Company | Enteric coated tablet and process for making |
US4794001A (en) | 1986-03-04 | 1988-12-27 | American Home Products Corporation | Formulations providing three distinct releases |
GB2189699A (en) | 1986-04-30 | 1987-11-04 | Haessle Ab | Coated acid-labile medicaments |
GB2189698A (en) | 1986-04-30 | 1987-11-04 | Haessle Ab | Coated omeprazole tablets |
US5026560A (en) | 1987-01-29 | 1991-06-25 | Takeda Chemical Industries, Ltd. | Spherical granules having core and their production |
US4808413A (en) | 1987-04-28 | 1989-02-28 | E. R. Squibb & Sons, Inc. | Pharmaceutical compositions in the form of beadlets and method |
JP2643222B2 (en) | 1988-02-03 | 1997-08-20 | エーザイ株式会社 | Multi-layer granules |
US4925675A (en) | 1988-08-19 | 1990-05-15 | Himedics, Inc. | Erythromycin microencapsulated granules |
US5026559A (en) | 1989-04-03 | 1991-06-25 | Kinaform Technology, Inc. | Sustained-release pharmaceutical preparation |
CA2030581C (en) * | 1989-11-24 | 2000-06-27 | Gunther Atzl | Pancreatin preparations |
US5158777A (en) * | 1990-02-16 | 1992-10-27 | E. R. Squibb & Sons, Inc. | Captopril formulation providing increased duration of activity |
US5175003A (en) * | 1990-04-06 | 1992-12-29 | Biosytes Usa, Inc. | Dual mechanism controlled release system for drug dosage forms |
DE4031881C2 (en) * | 1990-10-08 | 1994-02-24 | Sanol Arznei Schwarz Gmbh | Solvent-free, oral sustained-release pharmaceutical preparation and process for its preparation |
HUT74642A (en) * | 1990-12-21 | 1997-01-28 | Richardson Vicks Inc | Polyamine drug-resin complex |
NZ243567A (en) * | 1991-07-22 | 1995-04-27 | Bristol Myers Squibb Co | Pharmaceutical oral formulation of a dideoxy purine nucleoside comprising the nucleoside together with a water-insoluble antacid buffering composition |
US5225202A (en) * | 1991-09-30 | 1993-07-06 | E. R. Squibb & Sons, Inc. | Enteric coated pharmaceutical compositions |
US5350584A (en) | 1992-06-26 | 1994-09-27 | Merck & Co., Inc. | Spheronization process using charged resins |
ES2173096T3 (en) | 1992-08-05 | 2002-10-16 | Faulding F H & Co Ltd | PHARMACEUTICAL COMPOSITION PELETIZED. |
SE9302395D0 (en) * | 1993-07-09 | 1993-07-09 | Ab Astra | NEW PHARMACEUTICAL FORMULATION |
US5536507A (en) | 1994-06-24 | 1996-07-16 | Bristol-Myers Squibb Company | Colonic drug delivery system |
US5733575A (en) | 1994-10-07 | 1998-03-31 | Bpsi Holdings, Inc. | Enteric film coating compositions, method of coating therewith, and coated forms |
US5686106A (en) | 1995-05-17 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form for colonic delivery |
SG80553A1 (en) | 1995-07-20 | 2001-05-22 | Tanabe Seiyaku Co | Pharmaceutical preparation in form of coated capsule releasable at lower part of digestive tract |
US5789014A (en) | 1995-12-25 | 1998-08-04 | Shin-Etsu Chemical Co., Ltd. | Method of manufacturing a solid preparation coated with non-solvent coating |
DE19626045C2 (en) * | 1996-06-28 | 1998-12-03 | Klinge Co Chem Pharm Fab | A stable dosage form for oral administration containing omeprazole as the active ingredient and methods of making the same |
WO1999027917A1 (en) * | 1997-11-28 | 1999-06-10 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Medicament preparation in the form of a tablet or pellet for acid-labile active substances |
UA69413C2 (en) * | 1998-05-22 | 2004-09-15 | Брістол-Майерс Сквібб Компані | Enteric coated pharmaceutical composition, pharmaceutical composition in form of spheroid beads, method for manufacturing pharmaceutical composition |
-
1998
- 1998-06-08 UA UA2001021131A patent/UA73092C2/en unknown
- 1998-08-06 BR BR9815948-8A patent/BR9815948A/en not_active Application Discontinuation
- 1998-08-06 RO ROA200100021A patent/RO121082B1/en unknown
- 1998-08-06 NZ NZ508298A patent/NZ508298A/en not_active IP Right Cessation
- 1998-08-06 AU AU88983/98A patent/AU750388B2/en not_active Expired
- 1998-08-06 PL PL98345774A patent/PL195587B1/en unknown
- 1998-08-06 CN CNB988141736A patent/CN1195499C/en not_active Expired - Lifetime
- 1998-08-06 AT AT98940790T patent/ATE268165T1/en active
- 1998-08-06 PT PT98940790T patent/PT1098635E/en unknown
- 1998-08-06 RU RU2001104535/14A patent/RU2201217C2/en active
- 1998-08-06 DK DK98940790T patent/DK1098635T3/en active
- 1998-08-06 CZ CZ20010215A patent/CZ301557B6/en not_active IP Right Cessation
- 1998-08-06 EE EEP200100033A patent/EE05021B1/en unknown
- 1998-08-06 ID IDW20010105A patent/ID27019A/en unknown
- 1998-08-06 KR KR10-2001-7000742A patent/KR100535954B1/en not_active IP Right Cessation
- 1998-08-06 DE DE69824319T patent/DE69824319T2/en not_active Expired - Lifetime
- 1998-08-06 IL IL13970198A patent/IL139701A0/en not_active IP Right Cessation
- 1998-08-06 EP EP98940790A patent/EP1098635B1/en not_active Expired - Lifetime
- 1998-08-06 GE GEAP19985714A patent/GEP20032912B/en unknown
- 1998-08-06 HU HU0102659A patent/HU226492B1/en active IP Right Revival
- 1998-08-06 TR TR2000/03577T patent/TR200003577T2/en unknown
- 1998-08-06 ES ES98940790T patent/ES2221188T3/en not_active Expired - Lifetime
- 1998-08-06 CA CA002337885A patent/CA2337885C/en not_active Expired - Fee Related
- 1998-08-06 WO PCT/US1998/016323 patent/WO2000003696A1/en active IP Right Grant
- 1998-08-06 SK SK1883-2000A patent/SK285152B6/en not_active IP Right Cessation
- 1998-08-06 JP JP2000559831A patent/JP2002520350A/en active Pending
-
1999
- 1999-05-20 ZA ZA9903446A patent/ZA993446B/en unknown
- 1999-07-03 EG EG80099A patent/EG23944A/en active
- 1999-07-14 CO CO99044569A patent/CO5090840A1/en unknown
- 1999-07-16 AR ARP990103526A patent/AR019934A1/en not_active Application Discontinuation
-
2000
- 2000-04-14 US US09/549,455 patent/US6331316B1/en not_active Expired - Lifetime
-
2001
- 2001-01-12 LT LT2001003A patent/LT4844B/en not_active IP Right Cessation
- 2001-01-16 NO NO20010260A patent/NO330554B1/en not_active IP Right Cessation
- 2001-01-31 BG BG105203A patent/BG65443B1/en unknown
- 2001-02-12 LV LV010019A patent/LV12638B/en unknown
- 2001-05-25 US US09/866,501 patent/US6569457B2/en not_active Expired - Lifetime
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5422121A (en) * | 1990-11-14 | 1995-06-06 | Rohm Gmbh | Oral dosage unit form |
US5556839A (en) * | 1991-04-29 | 1996-09-17 | Eli Lilly And Company | Form II Dirithromycin |
US5326570A (en) * | 1991-07-23 | 1994-07-05 | Pharmavene, Inc. | Advanced drug delivery system and method of treating psychiatric, neurological and other disorders with carbamazepine |
US5510114A (en) * | 1993-05-18 | 1996-04-23 | Instituto Biochimico Italiano Giovanni Lorenzini S.P.A. | Slow release pharmaceutical composition containing a bile acid as an active ingredient |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
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US6569461B1 (en) | 1999-03-08 | 2003-05-27 | Merck & Co., Inc. | Dihydroxy open-acid and salts of HMG-CoA reductase inhibitors |
JP2003522139A (en) * | 2000-02-10 | 2003-07-22 | ビーピーエスアイ ホールディングス,インコーポレーテッド | Acrylic enteric coating composition |
WO2003009699A3 (en) * | 2001-07-23 | 2003-08-28 | Walcom Animal Science I P 5 Lt | Composition comprising cysteamine for specific use in poultry raising and egg production |
WO2003009699A2 (en) * | 2001-07-23 | 2003-02-06 | Walcom Animal Science (I.P.5) Limited | Composition comprising cysteamine for specific use in poultry raising and egg production |
WO2003053419A1 (en) * | 2001-12-20 | 2003-07-03 | Chugai Seiyaku Kabushiki Kaisha | Coated tablets and process for producing the same |
EP1556010A4 (en) * | 2002-10-31 | 2007-12-05 | Supergen Inc | Pharmaceutical formulations targeting specific regions of the gastrointestinal tract |
EP1556010A2 (en) * | 2002-10-31 | 2005-07-27 | SuperGen, Inc. | Pharmaceutical formulations targeting specific regions of the gastrointestinal tract |
WO2004071403A2 (en) | 2003-02-12 | 2004-08-26 | Lek Pharmaceuticals D.D. | Coated particles and pharmaceutical dosage forms |
WO2004071403A3 (en) * | 2003-02-12 | 2005-02-24 | Lek Pharmaceuticals | Coated particles and pharmaceutical dosage forms |
EP1744782A1 (en) * | 2004-04-10 | 2007-01-24 | Hanmi Pharm. Co., Ltd. | Sustained release formulation for oral administration of hmg-coa reductase inhibitor and method for the preparation thereof |
EP1744782A4 (en) * | 2004-04-10 | 2011-02-16 | Hanmi Holdings Co Ltd | Sustained release formulation for oral administration of hmg-coa reductase inhibitor and method for the preparation thereof |
US11744803B2 (en) | 2005-07-29 | 2023-09-05 | Stichting Groningen Centre for Drug Rese | PH-controlled pulsatile delivery system, methods for preparation and use thereof |
WO2007048233A1 (en) * | 2005-10-24 | 2007-05-03 | Orbus Pharma Inc. | Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist |
WO2009063320A3 (en) * | 2007-11-14 | 2010-03-18 | Blanver Farmoquimica, Ltda | Solid pharmaceutical composition of ded anosine |
US20190111001A1 (en) * | 2016-03-30 | 2019-04-18 | University Of Maryland, Baltimore | Microparticulate system for colonic drug delivery |
WO2017191501A2 (en) | 2016-05-04 | 2017-11-09 | D'oosterlynck André | Simmondsin formulation |
WO2020212822A1 (en) * | 2019-04-17 | 2020-10-22 | Amruth Gowda Doddaveerappa | Multi-component pharmaceutical single dosage forms and process employed thereof |
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