WO2013030726A1 - Diffusion de médicament programmé - Google Patents

Diffusion de médicament programmé Download PDF

Info

Publication number
WO2013030726A1
WO2013030726A1 PCT/IB2012/054258 IB2012054258W WO2013030726A1 WO 2013030726 A1 WO2013030726 A1 WO 2013030726A1 IB 2012054258 W IB2012054258 W IB 2012054258W WO 2013030726 A1 WO2013030726 A1 WO 2013030726A1
Authority
WO
WIPO (PCT)
Prior art keywords
core
coating
calcium
tablet
pharmaceutical composition
Prior art date
Application number
PCT/IB2012/054258
Other languages
English (en)
Inventor
Rahul Sudhakar Dabre
Ananda Haranath UPPALA
Moinuddin SYED
Girish Kumar Jain
Original Assignee
Wockhardt Limited
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
Application filed by Wockhardt Limited filed Critical Wockhardt Limited
Publication of WO2013030726A1 publication Critical patent/WO2013030726A1/fr

Links

Classifications

    • 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
    • A61K9/282—Organic compounds, e.g. fats
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • 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
    • A61K9/2813—Inorganic compounds
    • 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
    • A61K9/2893—Tablet coating processes
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Definitions

  • the present invention discloses programmed release pharmaceutical compositions of one or more active substances with a coating of co-processed glyceryl behenate and inorganic calcium salts, and compositions containing such coating.
  • the invention also relates to the dosage forms of specific geometry, which advantageously delays the release of the active substance from the core for a period of about 2 hours to about 10 hours after oral administration.
  • Circadian rhythms are physical, mental and behavioral changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism's environment. Circadian rhythms are produced by natural factors within the body, but they are also affected by signals from the environment. Light is the main cue influencing circadian rhythms, turning on or turning off genes that control an organism's internal clocks. Circadian rhythms can change sleep-wake cycles, hormone release, body temperature and other important bodily functions. For example, an asthmatic attack generally happens in the early morning, the stomach pH decreases during the night and in some hypertension diseases the pressure value is higher during the daytime, while a decrease occurs during the night.
  • rhythm disorders have been well documented in conditions such as asthma, arthritis, epilepsy, migraine, allergic rhinitis, cardiovascular disease (myocardial infarction, angina, stroke), chronic inflammation and pain, such as rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and peptic ulcer disease, with particular times where symptoms are more prominent and/or exacerbated. Treating these conditions require different amounts of drug at particular times, which synchronize the circadian cycle and provide adequate relief. Immediate release dosage forms may be impractical if the symptoms of the disease are pronounced during the night or early morning.
  • modified release dosage forms with zero order drug release theoretically leads to controlled and constant levels of drug in plasma throughout the day and at times may not be sufficient to synchronize the biological response i.e. they do not provide extra therapeutic levels at the time of pronounced symptoms. Further, the modified release dosage forms may produce adverse effects with little therapeutic benefit due to unwanted plasma drug concentration at other times of day.
  • Inorganic salt of calcium ion is available as Emcompress (Edward mendell, USA), A Tab ® (Rhodia, USA), Di Tab ® (Rhodia, USA), Fujicalin ® (Fuji Chemical Industry, Japan), Calstar (FMC Biopolymer) which contains dicalcium phosphate; Tricalcium phosphate is available as Tri Tab ® (Rhodia, USA); Calcium sulphate is available as Delaflo ® (JWS Delavau, USA); Calcium lactate pentahydrate is available as Puracal DC ® (Purac, USA); Calcium lactate trihydrate is available as Puracal TP ® (Purac, USA).
  • Dicalcium phosphate also known as calcium hydrogen orthophosphate dihydrate; calcium monohydrogen phosphate dihydrate; Di-Cafos; dicalcium orthophosphate; DI-TAB; E341 ; Emcompress; phosphoric acid calcium salt (1 :1 ) dihydrate; and secondary calcium phosphate.
  • Dicalcium phosphate is the most common inorganic salt used in direct compression as a filler-binder. The milled material is typically used in wet-granulated, roller-compacted or slugged formulations. The 'unmilled' or coarse-grade material is typically used in direct-compression formulations. Dibasic calcium phosphate dihydrate is nonhygroscopic and stable at room temperature.
  • dibasic calcium phosphate dihydrate is abrasive and a lubricant is required for tableting. Water of crystallization of dicalcium phosphate dihydrate could possible be released during processing and thus chemically interact with hydrolysable drug.
  • dicalcium phosphate is insoluble and very abrasive, which generally leads to reduced tooling life due to wear on the equipment during tablet manufacture.
  • High levels of lubricants are required to overcome the abrasiveness, but elevated levels of hydrophobic lubricants can impact the mechanical strength of the tablets and disintegration/dissolution performance.
  • dicalcium phosphate due to the propensity of dicalcium phosphate towards brittleness, it tends to exhibit failure in a plane normal to the compaction axis, i.e. experience tablet capping and lamination phenomena.
  • dicalcium phosphate has been modulated by the use of glyceryl behenate.
  • modified dicalcium phosphate has been used as an excipient in immediate and non-immediate release dosage forms.
  • use of such modified excipient as coating aid has not been explored let alone its advantages in exhibiting programmed drug delivery.
  • Glyceryl dibehenate is a mixture of glycerol esters. It is also known as Compritol 888 ATO; 2,3-dihydroxypropyl docosanoate; docosanoic acid, 2,3-dihydroxypropyl ester; E471 ; glycerol behenate; glycerol! dibehenas; and glyceryl monobehenate. It is a mixture of diacylglycerols, mainly dibehenoylglycerol, together with variable quantities of mono- and triacylglycerols.
  • Glyceryl behenate is used in cosmetics, foods, and oral pharmaceutical formulations.
  • glyceryl behenate is mainly used as a lubricant in the preparation of oral tablets and capsules. It has also been investigated for use in the preparation of sustained-release tablets; as a matrix-forming agent for the controlled release of water-soluble drugs; and it can also be used as a hot-melt coating agent sprayed onto a powder or drug-loaded sugar beads and granules. It may also be incorporated via extrusion/spheronization into pellets, which can be further compressed into tablets.
  • programmed release formulations suffer from the disadvantages that sometimes neither the minimum quantity of active substance is released therefrom "in vitro" after fixed intervals (programmed- release profile with indication of the minimum amount to be released at fixed intervals), nor are they are immune to the influence and possible variations of the preparation during the aging or storage thereof (stability of the programmed-release rate of the preparation over time).
  • lag phase in most of the programmed release formulations is dependent on geometry of dosage form such as tablet geometry or presence of weak points in the tablet. This leads to uneven rupture of the coating, thus leading to variation in drug release.
  • Undesired batch-to-batch variation in release of the active ingredient is common with such type of dosage form.
  • Coating thickness is another detrimental factor affecting the lag time. Improper positioning and thickness of the coating over the core may lead to intra-subject and intersubject variance in bioavailability.
  • U.S. Patent No. 7,364,755 discloses a modified calcium phosphate excipient with a fatty acid wax in a weight ratio of 50:50 to 95:5.
  • PCT Patent Application No. 2005013953 discloses an extended release tablet wherein the matrix material is co-processed with calcium phosphate and fatty acid wax having a ratio within the range of 85: 15 to 65: 35, respectively.
  • U.S. Patent Application No. 20060057200 discloses a tablet composition wherein the ratio of the thickness of the press coating on the sides of the tablet to the upper side or lower side is preferably about 2.2-2.6mm (for side edges): about 1 .2- 1 .6mm for the upper side and about 1 .0-1 .4 mm for lower side of the tablet.
  • the '200 application discloses the use of glyceryl behenate, calcium phosphate and povidone in coating composition, by using wet granulation process, for delaying the release of active substance.
  • U.S. Patent Application No. 200701 10807 discloses a press-coated tablet comprising a core containing an drug substance, and a coating, the core disposed within the coating such that the coating has a first thickness about an axis A-B and a thickness about an orthogonal axis X-Y, such that the coating about the axis X-Y is thicker than the coating about the axis A-B, to provide a lag time of between about 2 hours to about 6 hours.
  • U.S. Patent Application No. 20100196427 discloses a delayed-release dosage form of a glucocorticoid in which the release is delayed for a time period of 2-10 hours after intake.
  • the '427 application disclose the use of glyceryl behenate, calcium phosphate and povidone in coating composition, by using wet granulation process, for delaying the release of active substance.
  • U.S. Patent Application No. 20100222312 ('312) and PCT Publication No. 2010084188 disclose a method for treatment of asthma by administering a delayed- release dosage form of a glucocorticoid to a subject in need thereof.
  • the release of the active substance is delayed for a time period of 2-1 Oh after intake.
  • the '427 application disclose the use of glyceryl behenate, calcium phosphate and povidone in coating composition, by using wet granulation process, for delaying the release of active substance.
  • U.S. Patent No. 5,279,832 and European Patent No. 0495349 discloses a delayed release dosage form with a core, which contains the active substance and a coating.
  • the coating has selected areas which are thinner than the average thickness of the coating and/or areas which are predetermined rupture sites.
  • U.S. Patent No. 5,792,476 discloses a pharmaceutical composition of a glucocorticoid with a regulated sustained release such that at least 90% by weight of the glucocorticoid is released during a period of about 40-80 min, starting about 1 -3 hour after the entry of said glucocorticoid into the small intestine of a mammal.
  • U.S. Patent Nos. 6,372,254 and 6,730,321 discloses a press coated, pulsatile drug delivery system having an immediate-release compartment, which contains a compressed blend of an active agent and one or more polymers, substantially enveloped by an extended-release compartment, which contains a compressed blend of the active agent and hydrophilic and hydrophobic polymers.
  • U.S. Patent Application No. 20070243253 disclose a delayed release drug formulation comprising a particle with a core and a coating for the core, the core comprising a drug and the coating comprising a mixture of a first material which is susceptible to attack by colonic bacteria and a second material which has a pH threshold at about pH 5 or above, wherein the first material comprises at least one polysaccharide.
  • the present invention provides a programmed release pharmaceutical composition, comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said coating delays the release of the active substances from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a programmed release pharmaceutical composition, comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate prepared by melt granulation, wherein the said coating delays the release of the active substances from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a programmed release pharmaceutical composition, comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within the said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges the core.
  • the present invention provides a press-coated tablet, comprising of a core comprising one or more active substances and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges the core, wherein the dosage form delays the release of the active substance from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a press-coated tablet, comprising of a core comprising prednisone and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges the core, wherein the dosage form delays the release of the active substance from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a press-coated tablet, wherein the ratio of width of the tablet to the length of the tablet is less than the about 1 .33:1 .
  • the present invention provides a programmed release press- coated tablet, comprising of a core comprising one or more corticosteroid and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core, wherein the dosage form delays the release of the corticosteroid from the core for a period of about 2 hours to about 10 hours after oral administration.
  • a programmed release press-coated tablet comprising of a core comprising prednisone and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core, and the dosage form delays the release of the corticosteroid from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a method for delaying the release of one or more active substances from the core for a period between about 2 hours to about 10 hours, wherein the method comprise applying the coating composition to the core; wherein the coating composition comprises co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate.
  • the present invention provides a coating composition for delaying the release of one or more corticosteroid from the core for a period of about 2 hours to about 10 hours; wherein the coating composition comprises co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate optionally along with one or more pharmaceutically acceptable excipients.
  • the present invention provides a programmed release press- coated tablet, comprising of a core comprising of prednisone optionally with one or more corticosteroid and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core comprising co- processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core, wherein the dosage form delays the release of prednisone from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a method of treating circadian phase dependent pathologies such as asthma, arthritis, chronic inflammation and pain, such as rheumatoid arthritis and polymyalgia rheumatica wherein the method comprises administering a programmed release pharmaceutical composition, comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said coating delays the release of the active substances from the core for a period of about 2 hours to about 10 hours after oral administration to a patient in need of such treatment.
  • a programmed release pharmaceutical composition comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, where
  • Embodiments of the pharmaceutical composition may include one or more of the following features.
  • the pharmaceutically acceptable excipients may include diluents, disintegrants, binders, bulking agents, anti-adherents, anti-oxidants, buffering agents, colorants, flavoring agents, coating agents, plasticizers, stabilizers, preservatives, lubricants, glidants, chelating agents, and the like known to the art used either alone or in combination thereof.
  • the present inventors while trying to develop a programmed release dosage form, surprisingly found that when dosage forms comprising core coated with a coating composition comprising one or more inorganic salts of calcium ions co-processed with glyceryl behenate are exposed to aqueous media, the coating ruptures into two equal halves after a fixed time interval, thus releasing the active substance contained in the core.
  • the coating composition provides a lag phase of from about 2 hours to about 10 hours. This lag phase in the release of the active substance from the core can be modulated by changing the ratio of glyceryl behenate to inorganic salts of calcium ions in the coating composition.
  • the present inventors found that when glyceryl behenate and dicalcium phosphate were co-processed in a ratio of 30:70, a lag phase of about 4 hour and 05 minutes was observed. Further, when glyceryl behenate and dicalcium phosphate were co-processed in a ratio of 50:50, a lag phase of about 9 hours and 1 1 minutes was observed.
  • Present inventors have thus surprisingly discovered that such a coating composition has reduced the batch- to-batch variations of the formulation during the aging or storage thereof, and provides a consistent lag time with minimal variation. Further, the programmed release dosage form did not required specialized tooling for preparation.
  • the inventors found that by modifying the geometry of the press coated tablets containing a core coated with said coating, such that the thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core, delays the release of the active substances from the core for a period of about 2 hours to about 10 hours. For instance, when glyceryl behenate and dicalcium phosphate were co-processed in a ratio of 30:70 and press coated on the core with geometry of 1 .5mm thickness around the horizontal edge of the core and 1 .75mm thickness around the vertical edge of the core, a lag phase of about 4h to 5h can be observed.
  • dosage form refers to a pharmaceutical preparation in which dose or doses of one or more therapeutically active ingredients are included. It may be in form of, for example, a tablet, tablet-in-tablet, trilayer tablet, in-lay tablet, coated pellets, granules, multiple unit pellet system, pellets/granules filled in a capsule or combinations thereof.
  • programmed release refers to the release of drug after a certain lag phase, for example, 2 hours.
  • the drug release may be monophasic or biphasic.
  • the site of the release may be programmed too.
  • coating thickness around the vertical edges of the core of the tablet is used interchangeably with “length”.
  • length of the tablet refers to the thickness of the tablet, or the sides which comes in contact with the upper and lower punch.
  • coating thickness around the horizontal edges of the core of the tablet is used interchangeably with “width”.
  • width refers to diameter of the tablet, or the edges which are in contact to die while compression.
  • the term "Programmed release” as used herein refers to the release of drug after a certain lag phase.
  • the drug release may be monophasic or biphasic.
  • the site of the release may be programmed too.
  • Modified release dosage forms as used herein is defined (e.g. as by the United States Pharmacopoeia "USP") as those whose drug release characteristics of time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional immediate release dosage forms.
  • USP considers that the terms controlled release, prolonged release and sustained release are interchangeable.
  • modified-release controlled-release
  • control-releasing rate-controlled release
  • extended release extended release
  • prolonged-release prolonged release
  • sustained-release sustained release
  • sustained-release delayed release
  • delayed-release drug products are dosage forms that release the drugs at a time later than immediately after administration (i.e., these drug products exhibit a lag time in quantifiable plasma concentrations).
  • coatings e.g., enteric coatings
  • enteric coatings are intended to delay the release of medication until the dosage form has passed through the acidic medium of the stomach.
  • In vitro dissolution tests for these products should document that they are stable under acidic conditions and that they release the drug only in a neutral medium (e.g., pH 6.8).
  • “Lag time” is the time to disintegrate the tablet and to release the drug after administration of the programmed release dosage form.
  • co-processing or "co-processed mixture” as used herein refers to a combination of two or more excipients by an appropriate process, which involves but is not limited to wet granulation, melt granulation, etc.
  • bioavailable includes, but is not limited to the rate and extent to which the drug(s) become bioavailable to the site of action after administration.
  • Cmax is the highest plasma concentration of the drug attained within the dosing interval.
  • Tmax is the time period, which elapses after administration of the dosage form at which the plasma concentration of the drug attains the highest plasma concentration of drug attained within the dosing interval.
  • AUC 0 -t means area under plasma concentration-time curve from drug administration to last observed concentration at time t.
  • AUC 0 - a as used herein, means area under the plasma concentration-time curve extrapolated to infinite time.
  • mean when preceding a pharmacokinetic value (e.g. mean Tmax) represents the mean value of the pharmacokinetic value taken from a population of patients or healthy volunteers.
  • the programmed release pharmaceutical composition comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said coating delays the release of the active substance from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the programmed release pharmaceutical composition comprising of a core comprising one or more active substances optionally along with one or more pharmaceutically acceptable excipients, a coating, surrounding the said core, comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core and the said coating delays the release of the active substance from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the press-coated tablet comprising of a core comprising one or more active substances and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core, wherein the dosage form delays the release of the active substance from the core for a period of about 2 hours to about 10 hours after oral administration.
  • a wide variety of active agents may be employed in the present invention, which may be incorporated by reference to U.S. Patent Application No. 200701 10807 into the specification of the present invention.
  • Drugs for treating conditions the symptoms of which result from nocturnal circadian rhythms are particularly suitable. Accordingly, drugs for treating incontinence, sleep disorders, apnoea, asthma, epilepsy, bronchitis, parkinsonism, rheumatoid arthritis, allergic rhinitis and ischaemic heart diseases, cluster and migraine headache, congestive heart failure, and depression are particularly suitable for use in tablets according to the present invention.
  • drug substances that are metabolized by cytochrome P450 are also particularly suitable, they include: Amitriptyline, caffeine, clomipramine, clozapine, fluvoxamine, haloperidol, imipramine, mexilitine, oestradiol, olanzepine, paracetamol, propranolol, tacrine, theophylline, warfarin, Bupropion, Cyclophosphamide, Celecoxib, Diclofenac, Flubiprofen, Ibuprofen, glimepirideindome, thacin, naproxen, phenytoin, piroxicam, tenoxicam, citalopram, diazepam, lansoprazole, omeprazole, pantoprozole, propanolol, topiramate, Alpranolol, chlorpromazine, clomipramine, codeine, Desipramine, dextromethorphan, diphenhydramine
  • Antihistamines e.g., azatadine maleate, brompheniramine maleate, carbinoxamine maleate, chlorpheniramine maleate, dexchlorpheniramine maleate, diphenhydramine hydrochloride, doxylamine succinate, methdilazine hydrochloride, promethazine, trimeprazine tartrate, tripelennamine citrate, tripelennamine hydrochloride and triprolidine hydrochloride);
  • Antihistamines e.g., azatadine maleate, brompheniramine maleate, carbinoxamine maleate, chlorpheniramine maleate, dexchlorpheniramine maleate, diphenhydramine hydrochloride, doxylamine succinate, methdilazine hydrochloride, promethazine, trimeprazine tartrate, tripelennamine citrate, tripelennamine hydrochloride and triprolidine hydrochloride);
  • Antibiotics e.g., penicillin V potassium, cloxacillin sodium, dicloxacillin sodium, nafcillin sodium, oxacillin sodium, carbenicillin indanyl sodium, oxytetracycline hydrochloride, tetracycline hydrochloride, clindamycin phosphate, clindamycin hydrochloride, clindamycin palmitate HCL, lincomycin HCL, novobiocin sodium, nitrofurantoin sodium, metronidazole hydrochloride); antituberculosis agents (e.g., isoniazid);
  • Cholinergic agents e.g., ambenonium chloride, bethanecol chloride, neostigmine bromide, pyridostigmine bromide;
  • Antimuscarinics e.g., anisotropine methylbromide, clidinium bromide, dicyclomine hydrochloride, glycopyrrolate, hexocyclium methylsulfate, homatropine methylbromide, hyoscyamine sulfate, methantheline bromide, hyoscine hydrobromide, oxyphenonium bromide, propantheline bromide, tridihexethyl chloride);
  • anisotropine methylbromide clidinium bromide, dicyclomine hydrochloride, glycopyrrolate, hexocyclium methylsulfate, homatropine methylbromide, hyoscyamine sulfate, methantheline bromide, hyoscine hydrobromide, oxyphenonium bromide, propantheline bromide, tridihexethyl chloride
  • Sympathomimetics e.g., bitolterol mesylate, ephedrine, ephedrine hydrochloride, ephedrine sulphate, orciprenaline sulphate, phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride, ritodrine hydrochloride, salbutamol sulphate, terbutaline sulphate);
  • Sympatholytic agents e.g., phenoxybenzamine hydrochloride
  • miscellaneous autonomic drugs e.g., nicotine
  • Iron preparations e.g., ferrous gluconate, ferrous sulphate
  • Haemostatics e.g., aminocaproic acid
  • Cardiac drugs e.g., acebutolol hydrochloride, disopyramide phosphate, flecainide acetate, procainamide hydrochloride, propranolol hydrochloride, quinidine gluconate, timolol maleate, tocainide hydrochloride, verapamil hydrochloride;
  • Antihypertensive agents e.g., captopril, clonidine hydrochloride, hydralazine hydrochloride, mecamylamine hydrochloride, metoprolol tartrate ); vasodilators (e.g., papaverine hydrochloride);
  • Non-steroidal anti-inflammatory agents e.g., choline salicylate, ibuprofen, ketoprofen, magnesium salicylate, meclofenamate sodium, naproxen sodium, tolmetin sodium
  • choline salicylate e.g., choline salicylate, ibuprofen, ketoprofen, magnesium salicylate, meclofenamate sodium, naproxen sodium, tolmetin sodium
  • Opiate agonists e.g., codeine hydrochloride, codeine phosphate, codeine sulphate, dextromoramide tartrate, hydrocodone bitartrate, hydromorphone hydrochloride, pethidine hydrochloride, methadone hydrochloride, morphine sulphate, morphine acetate, morphine lactate, morphine meconate, morphine nitrate, morphine monobasic phosphate, morphine tartrate, morphine valerate, morphine hydrobromide, morphine hydrochloride, propoxyphene hydrochloride);
  • codeine hydrochloride codeine phosphate, codeine sulphate, dextromoramide tartrate, hydrocodone bitartrate, hydromorphone hydrochloride, pethidine hydrochloride, methadone hydrochloride, morphine sulphate, morphine acetate, morphine lactate, morphine meconate, morphine nitrate
  • Anticonvulsants e.g., phenobarbital sodium, phenytoin sodium, troxidone, ethosuximide, valproate sodium
  • Tranquilizers e.g., acetophenazine maleate, chlorpromazine hydrochloride, fluphenazine hydrochloride, prochlorperazine edisylate, promethazine hydrochloride, thioridazine hydrochloride, trifluoroperazine hydrochloride, lithium citrate, molindone hydrochloride, thiothixine hydrochloride);
  • Chemotherapeutic agents e.g., doxorubicin, cisplatin, floxuridine, methotrexate, combinations thereof
  • Lipid lowering agents e.g., gemfibrozil, clofibrate, HMG-CoA reductase inhibitors, such as for example, atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin
  • atorvastatin e.g., gemfibrozil, clofibrate, HMG-CoA reductase inhibitors, such as for example, atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin
  • atorvastatin e.g., gemfibrozil, clofibrate, HMG-CoA reductase inhibitors, such as for example, atorvastatin, cerivastatin, fluvastatin, lov
  • H 2 -antagonists e.g., cimetidine, famotidine, nizatidine, ranitidine HCI
  • Anti-coagulant and anti-platelet agents e.g., warfarin, cipyridamole, ticlopidine
  • Bronchodilators e.g., albuterol, isoproterenol, metaproterenol, terbutaline
  • Stimulants e.g., benzamphetamine hydrochloride, dextroamphetamine sulphate, dextroamphetamine phosphate, diethylpropion hydrochloride, fenfluramine hydrochloride, methamphetamine hydrochloride, methylphenidate hydrochloride, phendimetrazine tartrate, phenmetrazine hydrochloride, caffeine citrate;
  • Barbiturates e.g., amylobarbital sodium, butabarbital sodium, secobarbital sodium
  • Sedatives e.g., hydroxyzine hydrochloride, methprylon
  • expectorants e.g., potassium iodide
  • Antiemetics e.g., benzaquinamide hydrochloride, metoclopropamide hydrochloride, trimethobenzamide hydrochloride
  • Antiemetics e.g., benzaquinamide hydrochloride, metoclopropamide hydrochloride, trimethobenzamide hydrochloride
  • Gastrointestinal drugs e.g., ranitidine hydrochloride
  • heavy metal antagonists e.g., penicillamine, penicillamine hydrochloride
  • Antithyroid agents e.g., methimazole
  • Genitourinary smooth muscle relaxants e.g., flavoxate hydrochloride, oxybutynin hydrochloride
  • Vitamins e.g., thiamine hydrochloride, ascorbic acid
  • Steroids particularly glucocorticoids (e.g., prednisolone, methylprednisolone, prednisone, cortisone, hydrocortisone, methylprednisolone, betamethasone, dexamethasone, triamcinolone).
  • Unclassified agents e.g., amantadine hydrochloride, colchicine, etidronate disodium, leucovorin calcium, methylene blue, potassium chloride, pralidoxime chloride.
  • the active agents suitable for use in the composition of the present invention are corticosteroids.
  • Suitable corticosteroids may be selected from one or more prednisone, prednisolone, methylprednisolone, cortisone, hydrocortisone, budesonide, dexamethasone, fludrocortisone, fluocortolone, cloprednole, deflazacort and triamcinolone.
  • the preferred corticosteroid is prednisone.
  • the programmed release press-coated tablet comprising of a core comprising one or more corticosteroids and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core comprising co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core.
  • the dosage form delays the release of the corticosteroid from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the programmed release press-coated tablet comprises a core comprising prednisone and optionally along with one or more pharmaceutically acceptable excipients, and a coating surrounding the said core comprising co- processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, wherein the said core is disposed within said coating such that the coating thickness around the horizontal edges of the core is less than or equal to the coating thickness around the vertical edges of the core, wherein the dosage form delays the release of the prednisone from the core for a period of about 2 hours to about 10 hours after oral administration.
  • the present invention provides a method for delaying the release of one or more active substances from the core for a period of about 2 hours to about 10 hours, wherein the method comprise applying the coating composition to the core; wherein the coating composition comprises glyceryl behenate co-processed with one or more inorganic salts of calcium ion.
  • the method for delaying the release of one or more corticosteroids from the core for a period of about 2 hours to about 10 hours comprise applying the coating composition to the core; wherein the coating composition comprises co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate.
  • the present invention provides a coating composition for delaying the release of one or more active substances from the core for a period of about 2 hours to 10 hours; wherein the coating composition comprises co-processed mixture of one or more inorganic salts of calcium ion and glyceryl behenate, optionally with one or more pharmaceutically acceptable excipients.
  • the core is composed of either an immediate release or controlled release pharmaceutical composition consisting of the active ingredient in admixture with suitable excipients. If necessary, the core can be protected by a water-soluble or water-insoluble film before coating with the coating composition of one or more inorganic salts of calcium ion co-processed with glyceryl behenate.
  • the core may be prepared by various techniques known in the art such as direct compression, dry granulation, melt granulation, wet granulation.
  • a core may contain 0.1 to 90% by weight of active substance.
  • the programmed release composition of the present invention is in the form of a tablet, a tablet-in-tablet, a trilayer tablet, an in-lay tablet, coated pellets, granules, multiple unit pellet system, and pellets/granules filled in a capsule.
  • the tablets may also be compressed in the form of two or more layer tablet or press- coated in the form of tab-in-tab or tab-in-tab-in-tab.
  • the penetration of aqueous fluid takes place through pores formed due to solubilization of the pore forming agent.
  • pore forming agent include one or more inorganic salts of calcium ion.
  • the shape of the dosage form may be square, rectangular, circular, oval, donut, cylindrical, pentagonal, hexagonal, heptagonal, octagonal, pillowed shaped or a centrally notched round tablet.
  • Inorganic salts of calcium ion include, but not limited to calcium phosphate, calcium phosphate dihydrate, calcium phosphate anhydrous, dibasic calcium phosphate, dibasic calcium phosphate monohydrate, dibasic calcium phosphate dihydrate, anhydrous dibasic calcium phosphate, monobasic calcium phosphate, tribasic calcium phosphate, calcium acetate, calcium carbonate, calcium chloride, calcium hydroxide, calcium pyrophosphate, calcium sulfate, calcium sulfate anhydrous, calcium sulfate dihydrate, or calcium sulfate hemihydrate.
  • the inorganic salt of calcium ion is calcium phosphate dehydrate, or dibasic calcium phosphate dehydrate, or mixture thereof.
  • the coating composition is prepared by co-processing glyceryl behenate and dicalcium phosphate with one or more pharmaceutically acceptable excipients.
  • the coating may be polymeric film and/or compression coating.
  • the co-processed (mixture of) glyceryl behenate and inorganic salts of calcium ion are prepared by melt granulation process.
  • the ratio of glyceryl behenate and inorganic salts of calcium ion in the co-processed coating mixture ranges from about 10:90 to about 90:10.
  • the ratio of glyceryl behenate and inorganic salts of calcium ion of the co-processed mixture in the coating ranges from about 15:85 to about 55:45.
  • the programmed release composition is provided in the form of a press coated tablet.
  • the coating over the core of the programmed release composition may be applied as a film coating, spray coat, multiple layer compression coating or as press coating.
  • the ratio of width of the composition to the length of the composition is less than the ratio of about 1 .33:1 .
  • the coating composition further comprises one or more hydrophilic polymer, hydrophobic polymer or non-polymeric rate controlling excipients.
  • Suitable hydrophillic polymers include, but not limited to cellulose derivatives; polyhydric alcohols; saccharides, gums and derivatives thereof; vinyl derivatives, polymers, copolymers or mixtures thereof; maleic acid copolymers; polyalkylene oxides or copolymers thereof; acrylic acid polymers and acrylic acid derivatives; or any combinations thereof.
  • Cellulose derivatives include, but are not limited to ethyl cellulose, methylcellulose, hydroxypropylmethylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl ethylcellulose, carboxymethylethyl cellulose, carboxy- ethylcellulose, carboxymethyl hydroxyethylcellulose, hydroxyethylmethyl carboxymethyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose (CMC), methylhydroxyethyl cellulose, methylhydroxypropyl cellulose, carboxymethyl sulfoethyl cellulose, sodium carboxymethyl cellulose, or combinations thereof.
  • Polyhydric alcohols include, but are not limited to polyethylene glycol (PEG) or polypropylene glycol; or any combinations thereof.
  • Saccharides, gums and their derivatives include, but are not limited to dextrin, polydextrin, dextran, pectin and pectin derivatives, alginic acid, sodium alginate, polygalacturonic acid, xylan, arabinoxylan, arabinogalactan, starch, hydroxypropyl starch, amylose and amylopectin, CMC agar; guar gum, locust bean gum, xanthan gum, karaya gum, tragacanth, carrageenan, acacia gum, arabic gum or gellan gum or the like; or any combinations thereof.
  • Vinyl derivatives, polymers, copolymers or mixtures thereof include, but are not limited to polyvinyl acetate, polyvinyl alcohol, mixture of polyvinyl acetate (8 parts w/w) and polyvinylpyrrolidone (2 parts w/w) (Kollidon SR), copolymers of vinyl pyrrolidone, vinyl acetate copolymers, polyvinylpyrrolidone (PVP); or combinations thereof.
  • Polyalkylene oxides or copolymers thereof include, but are not limited to, polyethylene oxide, polypropylene oxide, poly (oxyethylene)-poly (oxypropylene) block copolymers (poloxamers), or combinations thereof.
  • Maleic acid copolymers include, but are not limited to vinylacetate maleic acid anhydride copolymer, styrene maleic acid anhydride copolymer, styrene maleic acid monoester copolymer, vinylmethylether maleic acid anhydride copolymer, ethylene maleic acid anhydride copolymer, vinylbutyiether maleic acid anhydride copolymer, acrylonitrile methyl acrylate maleic acid anhydride copolymer, butyl acrylate, styrene maleic acid anhydride copolymer or the like or any combinations thereof.
  • Suitable acrylic acid polymers include any suitable polyacrylic acid polymers or carboxyvinyl polymers such as those available under the brand name carbopol.
  • Acrylic polymer may be include one or more, but not limited to acrylic acid and methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cynaoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl methacrylate), poly(methacrylic acid) (anhydride), methyl methacrylate, polymethacrylate, poly(methyl methacrylate), poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), and glycidyl methacrylate.
  • Suitable hydrophobic polymer include, but are not limited to waxes, which are esters of fatty acids with long chain monohydric alcohols natural waxes are often mixtures of such esters, and may also contain hydrocarbons Waxes employed in the present invention include, but are not limited to, natural waxes, such as animal waxes, vegetable waxes, and petroleum waxes, paraffin waxes, microcrystalline waxes, petrolatum waxes, mineral waxes), and synthetic waxes Specific examples include, but are not limited to spermaceti wax, carnauba wax, Japan wax, bayberry wax, flax wax, beeswax, yellow wax, Chinese wax, shellac wax, lanolin wax, sugarcane wax, candelilla wax, castor wax paraffin wax, microcrystalline wax, petrolatum wax, carbowax, and the like, or mixtures thereof.
  • waxes which are esters of fatty acids with long chain monohydric alcohols natural waxes are often mixtures of such esters,
  • Waxes are also monoglyceryl esters, diglyceryl esters, or; glyceryl esters (glycerides) and derivatives and mixtures thereof formed from a fatty acid having from about 10 to about 22 carbon atoms and glycerol, wherein one or more of the hydroxyl groups of glycerol are substituted by a fatty acid.
  • Glycerides employed in the present invention include, but are not limited to, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl dipalmitate, glyceryl tripalmitate, glyceryl monopalmitate, glyceryl palmitostearate, glyceryl dilaurate, glyceryl trilaurate, glyceryl monolaurate, glyceryl didocosanoate, glyceryl tridocosanoate, glyceryl monodocosanoate, glyceryl monocaproate, glyceryl dicaproate, glyceryl tricaproate, glyceryl monomyristate, glyceryl dimyristate, glyceryl trimyhstate, glyceryl monodecenoate, glyceryl didecenoate, glyceryl trideceno
  • Fatty acids include, but are not limited to hydrogenated palm kernel oil, hydrogenated peanut oil, hydrogenated palm oil, hydrogenated rapeseed oil, hydrogenated rice bran oil, hydrogenated soybean oil, hydrogenated sunflower oil, hydrogenated castor oil (Lubritab), hydrogenated cottonseed oil, and mixtures thereof.
  • Other fatty acids include, but are not limited to, decenoic acid, docosanoic acid, stearic acid, palmitic acid, lauric acid, myristic acid, or the like, or mixtures thereof.
  • Non-polymeric rate controlling excipients include, but are not limited to fats, waxes, fatty acids, fatty acid esters, long chain monohydric alcohol or their ester or any combinations thereof.
  • the programmed release composition of present invention further comprise one or more pharmaceutically acceptable excipient selected from the group consisting of diluents, fillers, binders, disintegrant, lubricants, glidants and colorant.
  • Suitable diluents include, but are not limited to one or more of lactose, lactose monohydrate, mannitol, sucrose, maltodextrin, dextrin, maltitol, sorbitol, xylitol, powdered cellulose, cellulose gum, microcrystalline cellulose, starch, calcium phosphate, or metal carbonate.
  • binders include, but are not limited to one or more of starch, gums, pregelatinized starch, polyvinyl prrolidone (PVP), copovidone, cellulose derivatives, such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC) and carboxymethyl cellulose (CMC) and their salts.
  • suitable lubricants include, but are not limited to one or more of talc, magnesium stearate, calcium stearate, polyethylene glycol, hydrogenated vegetable oils, stearic acid, sodium stearyl fumarate, talc and sodium benzoate.
  • compositions of the present invention may include a glidant such as, but not limited to, colloidal silica, silica gel, precipitated silica, or combinations thereof.
  • a glidant such as, but not limited to, colloidal silica, silica gel, precipitated silica, or combinations thereof.
  • Suitable disintegrants include, but are not limited to one or more of starch, croscarmellose sodium, crospovidone, and sodium starch glycolate.
  • composition of the invention optionally include usual auxiliaries known in the art such as saliva stimulating agents like citric acid, lactic acid, malic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid, tartaric acids; cooling sensation agents like maltitol, monomenthyl succinate, ultracool; stabilizers like gums, agar; taste masking agents like acrylic polymers, copolymers of acrylates, celluloses, resins; coloring agents like titanium dioxide, natural food colors, dyes suitable for food, drug and cosmetic applications and effervescing agents like citric acid, tartaric acid, sodium bicarbonate, sodium carbonate and the like.
  • auxiliaries such as saliva stimulating agents like citric acid, lactic acid, malic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid, tartaric acids; cooling sensation agents like maltitol, monomenthyl succinate, ultracool; stabilizers like gums, agar; taste masking agents like acrylic poly
  • the present invention further provides a method of treating circadian phase dependent pathologies such as asthma, arthritis, epilepsy, migraine, allergic rhinitis, cardiovascular disease, chronic inflammation, pain, rheumatoid arthritis, polymyalgia rheumatica and peptic ulcer, wherein the method comprises administering a pharmaceutical composition of the present invention to a patient in need of such treatment.
  • circadian phase dependent pathologies such as asthma, arthritis, epilepsy, migraine, allergic rhinitis, cardiovascular disease, chronic inflammation, pain, rheumatoid arthritis, polymyalgia rheumatica and peptic ulcer.
  • Example 1 Prednisone MR Tablets-1 , 2 and 5 mg
  • Example 2 Core Tablet Unit Composition
  • Thickness 2.70-2.83 mm
  • Tooling 8.0 mm round Flat Faced Beveled Edges debossed with '45' on one side and plain on other side.
  • Thickness 2.3-2.4 mm
  • Tooling 8.0 mm round FFBE embossed with W5 on one side and plain on other side. Description: Round, yellow colored, press/compression coated FFBE debossed with W5 on one side and plain on other side.
  • Thickness 5.70-6.10 mm
  • Coating material composition was prepared as described in Example 5 using melt granulation process.
  • Thickness 2.3-2.4 mm
  • Tooling 8.0 mm round FFBE embossed with W5 on one side and plain on other side. Description: Round, press/compression coated FFBE debossed with W5 on one side and plain on other side.
  • Thickness 5.70-6.10 mm
  • Example 13 Alprazolam MR Tablets- 0.5 and 1 mg
  • Coating material composition was prepared as described in Example 5 using melt granulation process.
  • Thickness 2.3-2.4 mm
  • Tooling 8.0 mm round FFBE embossed with W5 on one side and plain on other side. Description: Round, yellow colored, press/compression coated FFBE debossed with W5 on one side and plain on other side.
  • Thickness 5.70-6.10 mm
  • Example 17 Albuterol MR Tablets- 2 and 4 mg
  • Coating material composition was prepared as described in Example 5 using melt granulation process.
  • Thickness 2.3-2.4 mm
  • Tooling 8.0 mm round FFBE embossed with W5 on one side and plain on other side. Description: Round, press/compression coated FFBE debossed with W5 on one side and plain on other side.
  • Thickness 5.70-6.10 mm
  • Coating material composition was prepared as described in Example 5 using melt granulation process.
  • Thickness 2.4-2.5 mm
  • Tooling 8.0 mm round FFBE embossed with W5 on one side and plain on other side. Description: Round, press/compression coated FFBE debossed with W5 on one side and plain on other side.
  • Thickness 5.80-6.30 mm

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques à libération programmée d'une ou de plusieurs substances actives présentant un enrobage de béhénate de glycéryle et de sels de calcium inorganiques cotraités, et des compositions contenant un tel enrobage. L'invention concerne également des formes posologiques à géométrie spécifique, qui retardent avantageusement la libération de la substance active du noyau pendant une durée d'environ 2 à 10 heures après administration par voie orale.
PCT/IB2012/054258 2011-08-26 2012-08-23 Diffusion de médicament programmé WO2013030726A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
IN2397MU2011 2011-08-26
IN2398MU2011 2011-08-26
IN2396/MUM/2011 2011-08-26
IN2397/MUM/2011 2011-08-26
IN2398/MUM/2011 2011-08-26
IN2396MU2011 2011-08-26

Publications (1)

Publication Number Publication Date
WO2013030726A1 true WO2013030726A1 (fr) 2013-03-07

Family

ID=46875928

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2012/054258 WO2013030726A1 (fr) 2011-08-26 2012-08-23 Diffusion de médicament programmé

Country Status (1)

Country Link
WO (1) WO2013030726A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104721160A (zh) * 2015-03-27 2015-06-24 贾红瑞 一种醋酸泼尼松片剂及其制备方法
WO2016114726A1 (fr) * 2015-01-12 2016-07-21 Ilko Ilaç Sanayi Ve Ticaret Anonim Şirketi Comprimé de prednisone à libération retardée régulée dans le temps
US20160256451A1 (en) * 2015-03-06 2016-09-08 Develco Pharma Schweiz Ag Dosage of naloxone
WO2018156141A1 (fr) * 2017-02-24 2018-08-30 Hewlett-Packard Development Company, L.P. Impression en trois dimensions (3d) d'un comprimé pharmaceutique
CN114588124A (zh) * 2020-12-07 2022-06-07 江苏恒瑞医药股份有限公司 一种延迟释放的药物组合物

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0495349A2 (fr) 1991-01-15 1992-07-22 Degussa Aktiengesellschaft Composition d'agent actif destinée à être administrée oralement, notamment aux ruminants
US5792476A (en) 1996-12-19 1998-08-11 Abigo Medical Ab Sustained release glucocorticoid pharmaceutical composition
US6372254B1 (en) 1998-04-02 2002-04-16 Impax Pharmaceuticals Inc. Press coated, pulsatile drug delivery system suitable for oral administration
WO2004093843A1 (fr) * 2003-04-24 2004-11-04 Jagotec Ag Comprime a action retardee et a geometrie de noyau definie
WO2005013953A1 (fr) 2003-07-25 2005-02-17 Synthon B.V. Comprimes de besylate de venlafaxine a liberation prolongee
US20060057200A1 (en) 2004-09-10 2006-03-16 Nitec Pharma Ag Tablets with site- and time-controlled gastrointestinal release of active ingredient
US20070243253A1 (en) 2006-04-13 2007-10-18 School Of Pharmacy, University Of London Colonic drug delivery formulation
US7364755B2 (en) 2003-07-07 2008-04-29 Synthon Ip Inc. Modified calcium phosphate excipient
WO2010075080A1 (fr) * 2008-12-15 2010-07-01 Somnus Therapeutics, Inc. Méthode de traitement des insomnies
WO2010084188A1 (fr) 2009-01-26 2010-07-29 Nitec Pharma Ag Traitement de l'asthme par glucocorticoïde à libération retardée
US20100196427A1 (en) 2009-01-30 2010-08-05 Nitec Pharma Ag Delayed-release glucocorticoid treatment of rheumatoid arthritis by improving signs and symptoms, showing major or complete clinical response and by preventing from joint damage

Patent Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5279832A (en) 1991-01-15 1994-01-18 Degussa Ag Active-substance preparation for oral administration, especially to ruminants
EP0495349A2 (fr) 1991-01-15 1992-07-22 Degussa Aktiengesellschaft Composition d'agent actif destinée à être administrée oralement, notamment aux ruminants
US5792476A (en) 1996-12-19 1998-08-11 Abigo Medical Ab Sustained release glucocorticoid pharmaceutical composition
US6372254B1 (en) 1998-04-02 2002-04-16 Impax Pharmaceuticals Inc. Press coated, pulsatile drug delivery system suitable for oral administration
US6730321B2 (en) 1998-04-02 2004-05-04 Impax Pharmaceuticals, Inc. Press coated, pulsatile drug delivery system suitable for oral administration
US20070110807A1 (en) 2003-04-24 2007-05-17 Jagotec Ag Delayed release tablet with defined core geometry
WO2004093843A1 (fr) * 2003-04-24 2004-11-04 Jagotec Ag Comprime a action retardee et a geometrie de noyau definie
US7364755B2 (en) 2003-07-07 2008-04-29 Synthon Ip Inc. Modified calcium phosphate excipient
WO2005013953A1 (fr) 2003-07-25 2005-02-17 Synthon B.V. Comprimes de besylate de venlafaxine a liberation prolongee
DE102004043863A1 (de) * 2004-09-10 2006-03-16 Nitec Pharma Ag Tabletten mit orts- und zeitgesteuerter Wirkstofffreisetzung im Gastrointestinum
US20060057200A1 (en) 2004-09-10 2006-03-16 Nitec Pharma Ag Tablets with site- and time-controlled gastrointestinal release of active ingredient
US20070243253A1 (en) 2006-04-13 2007-10-18 School Of Pharmacy, University Of London Colonic drug delivery formulation
WO2010075080A1 (fr) * 2008-12-15 2010-07-01 Somnus Therapeutics, Inc. Méthode de traitement des insomnies
WO2010084188A1 (fr) 2009-01-26 2010-07-29 Nitec Pharma Ag Traitement de l'asthme par glucocorticoïde à libération retardée
US20100222312A1 (en) 2009-01-26 2010-09-02 Nitec Pharma Ag Delayed-release glucocorticoid treatment of asthma
US20100196427A1 (en) 2009-01-30 2010-08-05 Nitec Pharma Ag Delayed-release glucocorticoid treatment of rheumatoid arthritis by improving signs and symptoms, showing major or complete clinical response and by preventing from joint damage

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016114726A1 (fr) * 2015-01-12 2016-07-21 Ilko Ilaç Sanayi Ve Ticaret Anonim Şirketi Comprimé de prednisone à libération retardée régulée dans le temps
US20160256451A1 (en) * 2015-03-06 2016-09-08 Develco Pharma Schweiz Ag Dosage of naloxone
CN104721160A (zh) * 2015-03-27 2015-06-24 贾红瑞 一种醋酸泼尼松片剂及其制备方法
CN104721160B (zh) * 2015-03-27 2017-08-08 新乡医学院第一附属医院 一种醋酸泼尼松片剂及其制备方法
WO2018156141A1 (fr) * 2017-02-24 2018-08-30 Hewlett-Packard Development Company, L.P. Impression en trois dimensions (3d) d'un comprimé pharmaceutique
US11602502B2 (en) 2017-02-24 2023-03-14 Hewlett-Packard Development Company, L.P. Three-dimensional (3D) printing a pharmaceutical tablet
CN114588124A (zh) * 2020-12-07 2022-06-07 江苏恒瑞医药股份有限公司 一种延迟释放的药物组合物
CN114588124B (zh) * 2020-12-07 2023-10-20 江苏恒瑞医药股份有限公司 一种延迟释放的药物组合物

Similar Documents

Publication Publication Date Title
JP5005157B2 (ja) 時間治療（ｃｈｒｏｎｏｔｈｅｒａｐｅｕｔｉｃ）投与形態
US9278076B2 (en) Chronotherapeutic dosage forms
RU2435568C2 (ru) Таблетки с высвобождением активного ингредиента, происходящим в определенном месте и в определенное время
US20210220281A1 (en) Oral pharmaceutical compositions of mesalazine
KR101363563B1 (ko) 활성성분의 부위 및 시간 제어적 위장관 방출 정제
TW201206501A (en) Pharmaceutical compositions comprising hydromorphone and naloxone
WO2013030726A1 (fr) Diffusion de médicament programmé
RU2738114C2 (ru) Пероральные фармацевтические композиции никотинамида
WO2007065625A2 (fr) Compositions pharmaceutiques a base d'agents hypnotiques de courte duree d’action, disponibles sous formes a liberation modifiee, et procedes de preparation desdites formulations
CN114588124B (zh) 一种延迟释放的药物组合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12759830

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12759830

Country of ref document: EP

Kind code of ref document: A1