WO2014167442A1 - Compositions pharmaceutiques comprenant de l'acide mycophénolique ou des sels de celui-ci - Google Patents

Compositions pharmaceutiques comprenant de l'acide mycophénolique ou des sels de celui-ci Download PDF

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Publication number
WO2014167442A1
WO2014167442A1 PCT/IB2014/060080 IB2014060080W WO2014167442A1 WO 2014167442 A1 WO2014167442 A1 WO 2014167442A1 IB 2014060080 W IB2014060080 W IB 2014060080W WO 2014167442 A1 WO2014167442 A1 WO 2014167442A1
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WO
WIPO (PCT)
Prior art keywords
delayed release
pharmaceutical composition
composition
release pharmaceutical
mycophenolic acid
Prior art date
Application number
PCT/IB2014/060080
Other languages
English (en)
Inventor
Girish Kumar Jain
Rahul Sudhakar Dabre
Pankaj Umakant Attarde
Pankaj SONI
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
Priority claimed from IN1152MU2013 external-priority patent/IN2013MU01152A/en
Priority claimed from IN1150MU2013 external-priority patent/IN2013MU01150A/en
Priority claimed from IN1153MU2013 external-priority patent/IN2013MU01153A/en
Priority claimed from IN1151MU2013 external-priority patent/IN2013MU01151A/en
Publication of WO2014167442A1 publication Critical patent/WO2014167442A1/fr

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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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a delayed release pharmaceutical composition
  • a delayed release pharmaceutical composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition, lactose, microcrystalline cellulose and one or more pharmaceutically acceptable excipients.
  • the invention also includes process of preparing such composition and their use in prophylaxis of organ rejection in patients receiving allogeneic renal transplants.
  • MPA Mycophenolic acid
  • E is chemically designated as (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1 ,3- dihydroisobenzofuran-5-yl)-4-methylhex-4-enoic acid sodium salt and has the following structural formula:
  • Mycophenolic acid has poor bioavailability caused by undetermined factors such as drug complexation in the gastro-intestinal lumen, a narrow absorption window, and metabolism before absorption etc.
  • mycophenolate mofetil MMF
  • mycophenolate mofetil MMF
  • MPA mycophenolate mofetil
  • the patient compliance with mycophenolate mofetil is not ideal because of side-effects, such as gastro-intestinal side effects, which has resulted in development of various delayed release formulations that by passes the stomach environment.
  • mycophenolic acid as the sodium salt is a white to off-white, crystalline powder and is highly soluble in aqueous media at physiological pH and practically insoluble in 0.1 N hydrochloric acid.
  • the mycophenolate sodium has a tendency to precipitate in the stomach due to acidic environment. Consequently, this precipitation adversely affects the bioavailability of the active ingredient. It is therefore desirable that dissolution of mycophenolate compositions is prevented in the stomach and instead dissolution is delayed until the intestine in which the pH is more basic.
  • compositions comprising a mycophenolate salt that prevents release of the active ingredient in the stomach and instead provides it release in the upper intestinal tract.
  • Mycophenolic acid as delayed release formulation comprising mycophenolate sodium was approved in United States. It is commercially available in 180 mg or 360 mg strengths under the proprietary name Myfortic ® and marketed by Novartis.
  • Myfortic ® is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.
  • the sodium salt of mycophenolic acid was disclosed specifically in first time in South African Patent 68/4959.
  • U.S. Patent No. 6,025,391 discloses pharmaceutical compositions which have been modified to release pharmaceutically acceptable mycophenolate salt in the upper part of the intestinal tract.
  • the patent discloses a composition comprising an enteric coated pharmaceutically acceptable mycophenolate salt.
  • the patent further exemplifies an enteric coated capsule containing mycophenolate sodium particles mixed with silicon dioxide, lactose and magnesium stearate.
  • U.S. Patent No. 6,172,107 & 6,306,900 discloses a pharmaceutical composition comprising a mycophenolate salt, the composition being adopted to release mycophenolate in the upper part of the intestinal tract.
  • the delayed release of the active ingredient is provided by compositions having an enteric coating.
  • PCT Publication No. WO 2007/093346 discloses the use of mycophenolic acid in immunosuppression, particularly for prevention or treatment of transplant rejection and immuno-mediated and/or inflammatory diseases, wherein mycophenolic acid, the salt or the prodrug thereof is administered with an initial intensified dosage regimen.
  • the application also discloses an enteric coated composition of mycophenolate, or a salt or a prodrug thereof.
  • PCT Publication No. WO 2009/047799 discloses high dose extended release pharmaceutical compositions comprising mycophenolate sodium as active agent in an amount of from greater than 720 mg to about 1500 mg and one or more pharmaceutically acceptable excipients.
  • the dosage forms are meant for once or twice a day administration and provide in-vivo release of the drug in a sustained manner for a prolonged duration.
  • US Patent publication No. 20100210717 discloses a solid dosage form, e.g. a tablet, comprising mycophenolic acid or a mycophenolate salt and a process of its production.
  • the application discloses both accelerated and delayed release compositions.
  • the application further discloses enteric coated tablets comprising a pharmacologically effective amount of mycophenolic acid or mycophenolate salt present in an amount of from about 20% to about 95% by weight based on the total weight of the tablet.
  • US Patent publication No. 201 10086102 discloses a matrix controlled delayed release pharmaceutical composition comprising an active pharmaceutical ingredient including mycophenolic acid, or its pharmaceutically acceptable salt, or combinations thereof.
  • the composition disclosed in the application does not contain enteric coating.
  • composition may have significant effect on the release profile of the drug from the dosage form.
  • an oral delayed release pharmaceutical composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition and one or more pharmaceutically acceptable excipients.
  • an oral delayed release pharmaceutical composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition, lactose and microcrystalline cellulose (MCC); wherein the ratio of the amount of lactose to MCC is in the range of about 1 .0: 6.0 to about 6.0: 1 .0.
  • an oral delayed release pharmaceutical composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition, lactose and microcrystalline cellulose (MCC); wherein the ratio of the amount of lactose to MCC is in the range of about 1 .0: 6.0 to about 6.0: 1 .0 and the composition achieves the desired dissolution profile.
  • an oral delayed release pharmaceutical composition of mycophenolic acid or salts thereof comprising lactose and microcrystalline cellulose (MCC), and one or more pharmaceutically acceptable excipients, wherein the ratio of the amount of lactose to MCC is in the range of about 1 .0: 6.0 to about 6.0: 1 .0 and the composition achieves the desired dissolution profile.
  • MCC microcrystalline cellulose
  • an oral delayed release tablet comprising less than of about 45% of mycophenolic acid or salts by total weight of composition, lactose and microcrystalline cellulose (MCC); wherein the ratio of the amount of lactose to MCC is in the range of about 1 .0: 6.0 to about 6.0: 1 .0 and the composition achieves the desired dissolution profile.
  • an oral delayed release capsule comprising less than of about 45% of mycophenolic acid or salts by total weight of composition, lactose and microcrystalline cellulose (MCC); wherein the ratio of the amount of lactose to MCC is in the range of about 1 .0: 6.0 to about 6.0: 1 .0 and the composition achieves the desired dissolution profile.
  • an oral delayed release pharmaceutical composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition and one or more pharmaceutically acceptable excipients, characterized that the composition is bioequivalent to delayed release formulation of mycophenolic acid marketed under the trade name Myfortic®.
  • an oral pharmaceutical composition of mycophenolic acid or salts thereof comprising less than of about 45% of mycophenolic acid or salts by total weight of composition, characterized that the composition retains at least 90% potency of mycophenolic acid or salts thereof when stored at 25°C and 60% relative humidity or at 40 U C and 75% relative humidity for 3 months.
  • a process for the preparation of an oral pharmaceutical composition of mycophenolic acid or salts thereof comprises mixing of mycophenolic acid or salts thereof with one or more pharmaceutically acceptable excipients, subjecting the obtained blend to granulation and compression to form tablet followed by coating with delayed release polymer.
  • a process for the preparation of an oral pharmaceutical composition of mycophenolic acid or salts thereof comprises mixing of mycophenolic acid or salts thereof with one or more pharmaceutically acceptable excipients intra-granularly and extra-granularly, subjecting the obtained blend to granulation and compression to form tablet followed by coating with delayed release polymers.
  • an oral pharmaceutical composition comprising composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition and one or more pharmaceutically acceptable excipients, used for the prophylaxis / treatment of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.
  • the inventors of the present invention have surprisingly found that by using less than of about 45% of mycophenolic acid or salts thereof by total weight of composition and certain pharmaceutically acceptable excipients in legitimate amount, the delayed release dosage form of mycophenolate or its salt with desired release profile can be prepared.
  • the inventors have found that by using less than of about 45% of mycophenolic acid or salts thereof by total weight of composition and lactose to microcrystalline cellulose (MCC) in the amount ratio of about 1 .0: 6.0 to about 6.0: 1 .0; the pharmaceutical composition being well tolerated, convenient to administer, achieves the desired dissolution parameters and provides the desired release profile.
  • MMCC microcrystalline cellulose
  • the present invention relates to an oral delayed release pharmaceutical composition
  • an oral delayed release pharmaceutical composition comprising less than of about 45% of mycophenolic acid or salts by total weight of composition and one or more pharmaceutically acceptable excipients.
  • the delayed release pharmaceutical composition of the present invention comprises less than of about 45% of mycophenolic acid or salts by total weight of composition and lactose to microcrystalline cellulose (MCC) in the amount ratio of about 1 .0:6.0 to about 6.0:1 .0; the pharmaceutical composition being well tolerated, convenient to administer, achieves the desired dissolution parameters and provides the desired release profile.
  • MCC microcrystalline cellulose
  • delayed release comprises any pharmaceutically acceptable composition that prevents the release of the active agent in the stomach and provides, preferably in the upper part of the intestinal tract and allows the resorption of the active agent through the walls of the intestinal tract.
  • mycophenolic acid used throughout the specification refers to not only mycophenolic acid per se, but also mycophenolate sodium salts, other pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof.
  • the active pharmaceutical ingredient in the context of the present invention is selected from the group comprising mycophenolic acid, a pharmaceutically acceptable salt thereof and combinations thereof, such as mycophenolate sodium or mycophenolate mofetyl. Most preferably, the active pharmaceutical ingredient is mycophenolate sodium.
  • compositions of the present invention are described with particular reference to tablets, other types of oral solid dosage forms but not limited effervescent tablets, fast dispersible tablets, matrix tablets, minitablets, multilayer tablets, pulsed release tablets, pellets, capsules, granulates or powder form, may be produced and are encompassed within the scope of this invention.
  • compositions of the present invention can be prepared by any conventional process.
  • the compositions can be prepared by conventional granulation techniques such as wet granulation or direct compression or dry granulation.
  • the compositions are prepared using wet granulation.
  • the invention provides a process for preparing a pharmaceutical composition of the invention comprising: (i) mixing the mycophenolic acid or mycophenolate salt and pharmaceutically acceptable excipients, (ii) subjecting a mixture obtained in step (i) to granulation (iii) compressing the granulates obtained in step (ii) and pharmaceutically acceptable additives to form the tablet.
  • the obtained tablets were coated with delayed release polymers.
  • the polymer used for modifying the release of mycophenolic acid or salts thereof includes but not limited to water soluble or water insoluble polymer.
  • the delayed release polymer comprises but not limited to cellulose ester derivatives, cellulose ethers, acrylic resins such as methylacrylate copolymers, copolymers of maleic acid and phthalic acid derivatives, shellac, hydroxypropylmethylcellulose acetate succinate, or polyvinylacetate phthalate.
  • delayed release polymer comprises but not limited to cellulose acetate phthalate and trimellitate; methacrylic acid copolymers derived from methacrylic acid and esters thereof and especially hydroxypropyl methylcellulose phthalate.
  • Polymethacrylates include but not limited to those of molecular weight above 100,000 daltons based on methacrylic acid and methyl or ethyl methacrylate in a ratio of about 1 :1 .
  • Typical cellulose acetate phthalates have an acetyl content of 17-26% and a phthalate content of from 30-40% with a viscosity of ca. 45-90 cP.
  • Typical cellulose acetate trimellitates have an acetyl content of 17-26%, trimellityl content from 25-35% with a viscosity of ca. 15-20 cS.
  • hydroxypropyl methylcellulose phthalates examples include the hydroxypropyl content of from 6-10%, a methoxy content of from 20-24%, a phthalyl content of from 21 -27%.
  • the delayed release polymers as per the present invention may be present in the form of a coating or in the matrix.
  • the coating material may be used in an amount of from about 5 to 20% by weight, preferably about 10 to 15% by weight, more preferably about 10% by weight based on the total weight of the composition.
  • Suitable solvents for the delayed release coating includes but not limited to aqueous solvents, organic solvents or mixture thereof.
  • suitable organic solvents alcohol such as ethanol or a mixture of alcohols, a ketone such as acetone, halogenated hydrocarbons for example methylene chloride or mixtures of such solvents, example ethanol/acetone.
  • pharmaceutically acceptable excipients includes a pharmaceutically acceptable material, composition or vehicle, suitable for administering an active pharmaceutical ingredient. Each excipient should be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Excipients include diluents, binders, disintegrants, glidants, lubricants, flavoring, and others.
  • Diluents increase the bulk of a solid pharmaceutical composition.
  • Exemplary diluents for solid compositions include, but are not limited to, microcrystalline cellulose, microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates, potassium chloride, powdered cellulose, sodium chloride, sorbitol and talc.
  • Solid pharmaceutical compositions that are compacted into a dosage form, such as a tablet may include excipients whose functions include helping to bind the active ingredient and other excipients together after compression.
  • exemplary binders for solid pharmaceutical compositions include, but are not limited to, acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate and starch.
  • Disintegrants increase the dissolution rate of a compacted solid pharmaceutical composition in the patient's stomach, for example.
  • Exemplary disintegrants include, but are not limited to alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate and starch.
  • Glidants can be added to improve the flowability of a non-compacted solid composition and to improve the accuracy of dosing.
  • exemplary excipients that may function as glidants include colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate.
  • a lubricant can be added to the composition to reduce adhesion and ease the release of the product from the dye.
  • exemplary lubricants include, but are not limited to, magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.
  • the mycophenolate sodium, lactose anhydrous, pregelatinised starch, crospovidone & microcrystalline cellulose were Co-sifted through suitable sieve & mixed.
  • Binder solution was prepared by dissolving the povidone in mixture of Isopropyl alcohol & methylene chloride and mixed with previously obtained blend. The obtained wet mass formed was dried in achieve loss on drying (LOD) below 2 %. Dried granules were again passed through suitable mesh. The obtained granules were lubricated with previously sieved magnesium stearate and then compressed into tablets. The obtained uncoated tablets were finally coated with hydroxyl propylmethyl cellulose pthalate.
  • the mycophenolate sodium, lactose anhydrous, pregelatinised starch, crospovidone & microcrystalline cellulose were Co-sifted through suitable sieve & mixed.
  • Binder solution was prepared by dissolving the povidone in mixture of Isopropyl alcohol & methylene chloride and mixed with previously obtained blend. The obtained wet mass formed was dried in achieve loss on drying (LOD) below 2 %. Dried granules were again passed through suitable mesh. The microcrystalline cellulose, crospovidone and colloidal silicon dioxide were passed through suitable mesh and mixed extra granularly with intragranular formed granules. The obtained granules were lubricated with previously sieved magnesium stearate and then compressed into tablets. The obtained uncoated tablets were finally coated with hydroxyl propylmethyl cellulose pthalate.
  • the mycophenolate sodium, lactose anhydrous, pregelatinised starch, crospovidone & microcrystalline cellulose were Co-sifted through suitable sieve & mixed.
  • Binder solution was prepared by dissolving the povidone in mixture of Isopropyl alcohol & methylene chloride and mixed with previously obtained blend. The obtained wet mass formed was dried in achieve loss on drying (LOD) below 2 %. Dried granules were again passed through suitable mesh. The obtained granules were lubricated with previously sieved magnesium stearate and then compressed into tablets. The obtained uncoated tablets were finally coated with hydroxyl propylmethyl cellulose pthalate.
  • the mycophenolate sodium, lactose anhydrous, pregelatinised starch, crospovidone & microcrystalline cellulose were Co-sifted through suitable sieve & mixed.
  • Binder solution was prepared by dissolving the povidone in mixture of Isopropyl alcohol & methylene chloride and mixed with previously obtained blend. The obtained wet mass formed was dried in achieve loss on drying (LOD) below 2 %. Dried granules were again passed through suitable mesh. The obtained granules were lubricated with previously sieved magnesium stearate and then compressed into tablets. The obtained uncoated tablets were finally coated with hydroxyl propylmethyl cellulose pthalate.
  • the dissolution data illustrated above shows that formulation meets the enteric coating test by providing zero amount of drug release in acidic environment and provides drug release only at basic environment.

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

Abstract

La présente invention concerne de nouvelles compositions pharmaceutiques comprenant de l'acide mycophénolique ou un sel de mycophénolate. La présente invention concerne une composition pharmaceutique orale comprenant moins d'environ 45 % d'acide mycophénolique ou des sels par poids total de composition, du lactose, de la cellulose microcristalline et un ou plusieurs excipients pharmaceutiquement acceptables. La présente invention concerne en outre un procédé de préparation d'une telle composition et son utilisation dans la prophylaxie du rejet d'organe chez des patients recevant des allogreffes rénales.
PCT/IB2014/060080 2013-03-26 2014-03-24 Compositions pharmaceutiques comprenant de l'acide mycophénolique ou des sels de celui-ci WO2014167442A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
IN1151/MUM/2013 2013-03-26
IN1152/MUM/2013 2013-03-26
IN1150/MUM/2013 2013-03-26
IN1153/MUM/2013 2013-03-26
IN1152MU2013 IN2013MU01152A (fr) 2013-03-26 2014-03-24
IN1150MU2013 IN2013MU01150A (fr) 2013-03-26 2014-03-24
IN1153MU2013 IN2013MU01153A (fr) 2013-03-26 2014-03-24
IN1151MU2013 IN2013MU01151A (fr) 2013-03-26 2014-03-24

Publications (1)

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WO2014167442A1 true WO2014167442A1 (fr) 2014-10-16

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PCT/IB2014/060080 WO2014167442A1 (fr) 2013-03-26 2014-03-24 Compositions pharmaceutiques comprenant de l'acide mycophénolique ou des sels de celui-ci

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10835489B2 (en) 2018-03-09 2020-11-17 University Of Saskatchewan Modified release formulations of mycophenolate mofetil

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ZA684959B (en) 1967-11-22 1969-05-22 Lilly Co Eli Agents and methods for inhibiting the growth of malignant tumor cells in warm-blooded mammals
US6025391A (en) 1996-04-12 2000-02-15 Novartis Ag Enteric-coated pharmaceutical compositions of mycophenolate
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WO2007093346A1 (fr) 2006-02-13 2007-08-23 Novartis Ag Doses élevées d'acide mycophénolique (mpa)
US20080206322A1 (en) * 2004-08-31 2008-08-28 Novartis Ag Pharmaceutical Multiparticulate Composit Ion Comprising Mycophenolic Acid or Myco Phenolate Sodium and Combination Compositions with Rapamycin
WO2009047799A1 (fr) 2007-10-08 2009-04-16 Panacea Biotec Limited Forme posologique pharmaceutique à usage oral unitaire solide à haute dose de mycophénolate de sodium et son procédé de fabrication
US20100210717A1 (en) 2001-10-17 2010-08-19 Dederichs Juergen Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt
US20110086102A1 (en) 2009-10-13 2011-04-14 Teva Pharmaceutical Industries Ltd. Delayed release compositions
CN102793658A (zh) * 2012-08-23 2012-11-28 无锡福祈制药有限公司 一种含有麦考酚酸或麦考酚酸盐的骨架型制剂及其包衣片

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ZA684959B (en) 1967-11-22 1969-05-22 Lilly Co Eli Agents and methods for inhibiting the growth of malignant tumor cells in warm-blooded mammals
US6025391A (en) 1996-04-12 2000-02-15 Novartis Ag Enteric-coated pharmaceutical compositions of mycophenolate
US6172107B1 (en) 1996-04-12 2001-01-09 Novartis Ag Entric-coated pharmaceutical compositions
US6306900B1 (en) 1996-04-12 2001-10-23 Novartis Ag Enteric coated pharmaceutical compositions
US20100210717A1 (en) 2001-10-17 2010-08-19 Dederichs Juergen Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt
US20070036857A1 (en) * 2003-10-03 2007-02-15 Dieter Becker Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin
US20080206322A1 (en) * 2004-08-31 2008-08-28 Novartis Ag Pharmaceutical Multiparticulate Composit Ion Comprising Mycophenolic Acid or Myco Phenolate Sodium and Combination Compositions with Rapamycin
WO2007093346A1 (fr) 2006-02-13 2007-08-23 Novartis Ag Doses élevées d'acide mycophénolique (mpa)
WO2009047799A1 (fr) 2007-10-08 2009-04-16 Panacea Biotec Limited Forme posologique pharmaceutique à usage oral unitaire solide à haute dose de mycophénolate de sodium et son procédé de fabrication
US20110086102A1 (en) 2009-10-13 2011-04-14 Teva Pharmaceutical Industries Ltd. Delayed release compositions
CN102793658A (zh) * 2012-08-23 2012-11-28 无锡福祈制药有限公司 一种含有麦考酚酸或麦考酚酸盐的骨架型制剂及其包衣片

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"Hypromellose Phthalate: Pharmaceutical Excipients", 14 April 2014, article ANONYMOUS: "Hypromellose Phthalate: Pharmaceutical Excipients", XP055123885 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10835489B2 (en) 2018-03-09 2020-11-17 University Of Saskatchewan Modified release formulations of mycophenolate mofetil

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