WO2004087113A1 - Compositions pharmaceutiques pour liberation specifique dans le colon - Google Patents

Compositions pharmaceutiques pour liberation specifique dans le colon Download PDF

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Publication number
WO2004087113A1
WO2004087113A1 PCT/IB2004/001041 IB2004001041W WO2004087113A1 WO 2004087113 A1 WO2004087113 A1 WO 2004087113A1 IB 2004001041 W IB2004001041 W IB 2004001041W WO 2004087113 A1 WO2004087113 A1 WO 2004087113A1
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WO
WIPO (PCT)
Prior art keywords
coating
pharmaceutical composition
process according
core
ester
Prior art date
Application number
PCT/IB2004/001041
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English (en)
Inventor
Praveen Raheja
Shashikanth Isloor
Sanjeev Sethi
Rajiv Malik
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Ranbaxy Laboratories 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.)
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Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2004087113A1 publication Critical patent/WO2004087113A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/606—Salicylic acid; Derivatives thereof having amino groups
    • 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
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

  • the present invention relates to pharmaceutical compositions, and processes for their preparation, for oral administration that provides a colon specific delivery.
  • the pharmaceutical has a coating having thickness less than 60 ⁇ m.
  • Such active ingredients be administered in a dosage form that provides a high local concentration in the colon, but with minimal systemic side effects.
  • Such active ingredients are conventionally administered through a rectal route, by use of either suppositories or enemas. However, this is a less acceptable route and further does not deliver the active ingredient to the right side of colon, which is the desired site.
  • Mesalamine has been used for years as an oral dosage form for the treatment of Crohn's disease or irritable bowel syndrome. This dosage form is administered in the form of sulphasalazine, which splits into mesalamine and sulphapyridine by bacteria in the colon. However, the sulphapyridine produced leads to various undesirable side effects.
  • a delayed release dosage formulation that does not disintegrate in the stomach and releases gradually in the intestine is one of the viable options.
  • Polymers such as anionic polymers have been used for many years as coatings for tablets or other dosage forms to provide delayed or sustained release of the active ingredient.
  • Anionic polymers in particular, copolymers of the anionic polymer of methacrylic acid and its methyl ester provide coatings that release the drug depending on the pH of the medium and the ratio of acid to ester.
  • Such polymers are available under the trade name of Eudragit S and Eudragit L and are supplied by Rohm Pharma, GMBH, Darmstadt, Germany.
  • Eudragit S in which the ratio of free carboxyl group to ester group is approximately 1 :2, is insoluble in both gastric and intestinal juice.
  • Eudragit L with the above ratio of 1 : 1 is insoluble in gastric juice but dissolves readily in the intestine. Combinations of these two polymers are employed to obtain the desired release profile.
  • U.S. Patent No. 5,541,171 discloses a pharmaceutical composition that selectively administers mesalamine or pharmaceutical acceptable salt or ester thereof to the large intestine.
  • the dosage form has a 60-150 ⁇ m thick coating layer of the anionic copolymer of methacrylic acid and its methyl ester.
  • the polymers are insoluble in gastric juice and in intestinal juice at a pH that is below 7, and remains intact until it reaches the colon where it is soluble.
  • the commercially available, delayed release, mesalamine tablets available under the brand name of Asacol® is based on this concept. However, these tablets have been reported to occasionally be eliminated from the body without any release of the active ingredient or with variable bioavailability.
  • EP 1,004,297 discloses a pharmaceutical composition for oral administration in tablet form.
  • the tablet contains mesalamine and a film coating comprising terpolymer, wliich contains methylacrylate, methyl methacrylate and methacrylic acid monomer units in the chain.
  • the weight build up of film coating is between 5-7.5% by weight of the total weight of the core.
  • this dosage form does not give colon specific delivery.
  • WO 01/66094 discloses a controlled release oral solid dosage form for the administration of mesalamine into the colon.
  • the dosage form is a capsule filled with mesalamine-containing multiparticulates coated with a layer of polymer that is soluble at a pH greater than 6.5.
  • an oral pharmaceutical composition in the form of single dosage unit for selectively administering to the colon an active agent or its pharmaceutically acceptable salt or ester thereof.
  • the pharmaceutical composition includes a core and a coating.
  • the core includes an active agent or its pharmaceutically acceptable salt or ester thereof.
  • the coating includes a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 60 ⁇ m.
  • the core may be a tablet or a capsule.
  • the active agent may be one or more of prednisolone, indomethacin, ibuprofen, and mesalamine and, in particular, may be mesalamine.
  • the anionic copolymer of methacrylic acid and methacrylic methyl ester may be
  • the coating layer may have a thickness that is less than about 55 ⁇ m. In particular, the coating layer may have a thickness that is between about 25 ⁇ m and about 45 ⁇ m.
  • the anionic copolymer of methacrylic acid and methacrylic methyl ester may be soluble at a pH of about 7.
  • the pharmaceutical composition may further include a second coating layer.
  • the second coating layer may be an anionic copolymer of methacrylic acid with a ratio of 1 : 1 of free carboxylic acid to ester group.
  • the anionic copolymer of methacrylic acid may be Eudragit L.
  • the Eudragit L may be Eudragit L 100.
  • the core may further include one or more pharmaceutically acceptable excipients.
  • the pharmaceutically acceptable excipients may be one ore more of fillers, binders, lubricants, and disintegrants.
  • the coating may further include one or more coating additives.
  • the coating additives may be one or more of plasticizers, coloring agents, gloss producers, and lubricants/glidants.
  • the plasticizer in the coating layer may be one or more of triethyl citrate, diethyl phthalate, dibutyl phthalate and polyethylene glycol.
  • the plasticizer may be triethyl citrate.
  • the triethyl citrate may be used in the coating layer at a concentration of between about 15% to about 40% w/w.
  • an orally administered pharmaceutical composition in the form of single dosage unit for selectively administering to the colon mesalamine or its pharmaceutically acceptable salt or ester thereof.
  • the pharmaceutical composition includes a core, a first coating layer, and a second coating layer.
  • the core includes mesalamine or its pharmaceutically acceptable salt or ester thereof.
  • the first coating layer includes a less than 60 ⁇ m thick layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which ratio of free carboxyl to ester group is about 1:2 and the coating has a thickness that is less than 60 ⁇ m.
  • the second coating layer includes an anionic copolymer of methacrylic acid and methacrylic methyl ester in which ratio of free carboxyl to ester group is about 1:1.
  • a process for preparing an orally administered pharmaceutical composition in the form of single dosage unit for selective administration to the colon of an active agent or its pharmaceutically acceptable salt or ester thereof includes a granulating step, a compressing step, and a coating step.
  • the granulating step includes granulating an active agent and one or more pharmaceutically acceptable excipients.
  • the compressing step includes compressing the granules to form a core.
  • the coating step includes coating the core with a coating composition.
  • the coating composition includes an anionic copolymer of methacrylic acid and methacrylic methyl ester in which a ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 55 ⁇ m.
  • the coating composition may be coated over the core in the form of a solution or dispersion.
  • the solution or dispersion may be prepared in a solvent.
  • the solvent may be one or more of water, ethanol, methanol, isopropyl alcohol, chloroform, acetone, ether or mixtures thereof.
  • the solvent may be isopropyl alcohol.
  • Coating the core may include one or more of spray coating, fiuidized bed processing, and dip coating, hi particular, the core tablet may be coated using spray coating.
  • the core may be a tablet or a capsule.
  • the anionic copolymer of methacrylic acid and methacrylic methyl ester may include Eudragit S.
  • the coating layer may have a thickness that is less than about 55 ⁇ m. i particular, the coating layer may have a thickness that is between about 25 ⁇ m and about 45 ⁇ m.
  • the anionic copolymer of methacrylic acid and methacrylic methyl ester may be soluble at a pH of about 7.
  • the active agent may be one or more of prednisolone, indomethacin, ibuprofen, and mesalamine.
  • the active agent may be mesalamine.
  • the process may further include a second coating layer.
  • the second coating layer may be an anionic copolymer of methacrylic acid with a ratio of 1 : 1 of free carboxylic acid to ester group.
  • the anionic copolymer of methacrylic acid may be Eudragit L.
  • the Eudragit L may be Eudragit L 100.
  • the pharmaceutically acceptable excipients may be one or more of fillers, binders, lubricants, and disintegrants.
  • the coating may further include one or more coating additives.
  • the coating additives maybe one or more of plasticizers, coloring agents, gloss producers, and lubricants/glidants .
  • a method of treating ailments of the colon and/or rectum in a patient in need thereof includes administering an oral pharmaceutical composition in the form of single dosage unit that provides selective administration to the colon or rectum of an active agent or its pharmaceutically acceptable salt or ester thereof.
  • the pharmaceutical composition includes a core and a coating.
  • the core includes an active agent or its pharmaceutically acceptable salt or ester thereof.
  • the coating includes a layer of an anionic copolymer of methacrylic acid and methacrylic methyl ester in which the ratio of free carboxyl to ester group is about 1 :2 and the coating has a thickness that is less than 60 ⁇ m.
  • the coating layer may have a thickness that is less than about 55 ⁇ m.
  • the coating layer may have a thickness that is between about 25 ⁇ m and about 45 ⁇ m.
  • the inventors have developed pharmaceutical compositions for oral administration, and processes for the preparation of the pharmaceutical compositions, in the form of single dosage unit that specifically releases the drug in the colon.
  • the dosage form is coated with an anionic copolymer of methacrylic acid and methacrylic methyl ester, in which the ratio of free carboxyl to ester group is about 1 :2 and the thickness of coating layer is less than about 60 ⁇ m.
  • the thickness of the present invention is drastically lower than the dosage forms described in prior art. hi fact, the prior art states that the coating thickness should be at least 60 ⁇ m so that the formulation can reach the target area, i.e., the colon, in its whole state. Therefore, contrary to the teachings of the prior art, it has been found that tablets coated with a layer having a thickness less than 60 ⁇ m provides satisfactory protection of the core until it reaches the colon.
  • This invention provides a colonic delivery dosage form with a lesser thickness of the coating layer, which leads to a weight build up of less than 5% w/w.
  • the process of preparing the dosage form involves coating the solid dosage form itself and not coating the individual particles contained therein. This provides a process that results in a relatively inexpensive and easy to manufacture dosage form. Additionally, it provides for less processing time and polymer being used, but maintains the same release profile as the oral dosage forms described in the prior art. Further, the maximum plasma concentration (T max ) and lag time in release (T ⁇ a ), as evaluated by in vivo bioavailability studies, were comparable to Asacol DR tablets.
  • administering an active agent or its pharmaceutically acceptable salt or ester thereof selectively to the colon means the active agent or its pharmaceutically acceptable salt or ester thereof is released from a single dosage unit at a pH of about 7, i.e., at the pH of the colonic environment.
  • core as used herein includes tablets, capsules and the like used as single dosage units in the field of dispensing art.
  • Suitable active agents include compounds that are used conventionally in the treatment of colitis, ulcerative colitis, Crohn's disease and other disorders of the colon and/or rectum, including nonsteroidal anti-inflammatory compounds, such as salicylates, indomethacin and ibuprofen; steroids, such as prednisolone, hydrocortisone, prednisolone phosphate, beclomethasone propionate and valerate; compounds active in the relief of constipation or diarrhea; compounds active in the relief of spasms and improvement of motility, such as peppermint oil and other carminative essential oils; compounds for removal of excessive bile acids, such as cholestyramine; and antibacterial or antiparasitic compounds, such as erythromycin, chloroquine, iodochlorhydroxyquin, disodohydroxyquin, neomycin and tetracyclines.
  • This invention has particular application to dosage forms of prednisolone, indomethacin, ibupro
  • the core may include one or more fillers, binders, lubricants and/or disintegrants.
  • the core may be prepared by conventional procedures, such as dry granulation, wet granulation, direct compression, in case of tablets, or by filing, in case of capsules.
  • the core may be coated with a solution or dispersion of the coating composition.
  • the coating composition may include methylesterified methacrylic acid polymers and other coating additives. Methylesterified methacrylic acid polymers are available under the trade name of Eudragit S and Eudragit L and are supplied by Rohm Pharma.
  • Eudragit S is used for coating tablets, or other solid dosage forms, to make them impervious to water and gastric juices although it is soluble in neutral or slightly alkaline media, thus releasing the drug at a pH that is greater than 7.0.
  • Eudragit S is insoluble in gastric juices, but is readily soluble in intestinal juices.
  • Eudragit L dissolves at pH values greater than 6, whereas Eudragit S is soluble at pH values greater than 7, thus achieving local delivery in the colon.
  • the Eudragit S layer can be further coated with Eudragit L, such as Eudragit L 100 and/or Eudragit L 30D-55 to obtain the desired release profile.
  • Coating additives may include one or more of plasticizers, coloring agents, gloss producer and lubricants/glidants.
  • Suitable plasticizer may include one or more of diethyl phthalate, dibutyl phthalate, triethyl citrate and polyethylene glycol.
  • the plasticizers may present in an amount between about 15% to about 40%, and in particular, about 25% to about 30% by weight with respect to the acrylic acid copolymer.
  • a polymer solution or dispersion may be prepared in various solvents, such as water, ethanol, methanol, isopropyl alcohol, chloroform, acetone, ether or mixtures thereof.
  • the coating composition may be coated onto the solid dosage form using techniques, such as spray coating in a conventional coating pan, fluidized bed processing or dip coating.
  • the coating process provides a coating thickness of about 25 ⁇ m to about 55 ⁇ m, in particular, about 25 ⁇ m to about 45 ⁇ m, with the resulting weight build up being less than about 5% w/w.
  • composition A Composition of Core Tablets
  • a core was prepared containing mesalamine as the active ingredient and the following other ingredients:
  • Mesalamine was granulated in a rapid mix granulator using polyvinyl pyrrolidone dissolved in water. The resulting granules were then dried in a fluidized bed drier at 60°C. The granules then were blended with microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate and compressed using a 12 mm circular, standard concave tooling on a 16 station, single rotary compression machine at 20 rpm.
  • a coating composition was prepared in the form of a dispersion containing the following ingredients:
  • Triethyl citrate 18.0 g
  • Iron oxide red 1.20 g
  • Iron oxide yellow 0.30 g
  • Eudragit S-100 was dissolved in isopropyl alcohol. Triethyl citrate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets of composition A were pre- warmed to about 40°C and spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm 2 , to a weight build up of about 3% w/w (about 35 ⁇ m thick). The coated tablets were then dried in the coating pan at about 45°C to about 55°C.
  • a pan coater Frund Hi Coater
  • the coat thickness of tablets prepared according to composition A were measured using a micrometer.
  • the coats were then dried at about 40°C in an oven for 10 minutes.
  • the coating thickness was measured in the center and across the edges using a micrometer with a least count of 1 ⁇ m. The results of these measurements are listed in Table 2.
  • a dissolution study under stressed conditions was conducted in a USP apparatus type 2 on tablets prepared according to the composition A.
  • the study involved dissolution of the tablets for 2 hours in a pH of 1.2 (0.1 N HCl, 500 ml) followed by 4 hours at a pH of 4.5 (Acetate buffer, 900 ml) and 2 hours at a pH of 6.5 (Phosphate buffer, 900 ml).
  • the results of the study as shown in Table 3, clearly indicate that even under the stressed conditions encountered during variable gastric residence times in the stomach and intestine, mesalamine DR tablets provided a more consistent and predictable release profile, releasing mesalamine only at a pH above 7.2.
  • the objective of this study was to show that a formulation prepared by this invention releases mesalamine into the distal tract of the intestine and provides an activity and safety profile that is similar to or better then the one obtained with the equivalent commercial product.
  • a single dose (400 mg x 2) crossover, fully replicated and open randomized study was designed as a two treatment, four period study to compare the bioavailability of mesalamine DR 400 mg of the present invention and Asacol® DR 400 mg under fasting conditions.
  • Plasma levels of mesalamine were analyzed and the results indicated a higher absorption of the drag from the formulation produced according to present invention. It also indicated that no release of the drug occurred in the proximal region of the colon.
  • the pharmacokinetics results showed no significant difference in T ma ⁇ and T ⁇ ag values as shown in Table 4, while the maximum plasma concentration (C max ) and the area under the plasma concentration vs time curve (AUC) values were found to be higher in the case of the present formulation as compared to an equivalent product.
  • the cores of entire and partially disintegrated Asacol® tablets were found to be eliminated in the stool, whereas none of the tablets manufactured according to the present invention were eliminated as entire or partially disintegrated particles in the stool.
  • the formulation according to invention provided plasma parameters that were drastically higher than the commercially available formulation. This is evidence that the systemic absorption of mesalamine has increased, indicating a higher concentration of drag is available in the colon.
  • a core tablet was prepared containing mesalamine as the active ingredient and the following other ingredients: Mesalamine USP 400 mg
  • Mesalamine was granulated in a rapid mix granulator using polyvinyl pyrrolidone dissolved in water. The granules were then dried in a fluidized bed drier at 60°C. The granules were blended with microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate and then compressed using 12 mm circular standard, concave tooling on a 16 station, single rotary compression machine at 20 rpm.
  • Eudragit S was dissolved in isopropyl alcohol and triethyl citrate, talc and colors were dispersed in purified water. The two were mixed to obtain the coating composition.
  • Tablets of composition A were pre- warmed to about 40°C and spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm 2 , to a weight build up of about 3% w/w (about 35 ⁇ m thick) and the coated tablets were then dried in the coating pan at about 45°C to about 55°C.
  • Top coat Top coat:
  • a core tablet was prepared containing mesalamine as the active ingredient and the following other ingredients: Mesalamine USP 400 mg
  • Mesalamine was granulated in a rapid mix granulator using polyvinyl pyrrolidone dissolved in water. The granules were then dried in a fluidized bed drier at 60°C. The granules were blended with microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate, and magnesium stearate and then compressed using 12 mm circular standard, concave tooling on a 16 station single, rotary compression machine at 20 rpm, Tablets were coated with a subcoat of Opadry to a weight build up of 2% w/w of the core tablet.
  • Eudragit S was dissolved in isopropyl alcohol. Triethyl citrate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets of composition A were pre- warmed to about 40°C and spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm 2 , to a weight build up of about 3% w/w (about 40-50 ⁇ m thick). The coated tablets were then dried in the coating pan at about 45°C to about 55°C.
  • a pan coater Frund Hi Coater
  • Eudragit L was dissolved in isopropyl alcohol. Dibutyl phthalate, talc and colors were dispersed in purified water, and then the two were mixed to obtain the coating composition. Tablets were coated with the primary coat and were further spray coated in a pan coater (Freund Hi Coater) at an atomization pressure of 1-2 kg/cm 2 until obtaining a weight gain of 5% w/w of the primary coated tablet. The coated tablets were then dried in the coating pan at about 45°C to about 55°C. C. In vitro dissolution test
  • composition A An In vitro dissolution test was performed on composition A by following the method described in the United States Pharmacopoeia (USP) for delayed release tablets using a USP apparatus type 2. The results of the dissolution testing of the tablet prepared by Example 3 are shown in Table 5.
  • USP United States Pharmacopoeia

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
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  • Organic Chemistry (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La prEsente invention concerne des compositions pharmaceutiques et leurs procEdEs de prEparation, lesdites compositions Etant destinEes A une administration par voie orale assurant une libEration spEcifique dans le cOlon. Le mEdicament possEde un enrobage d'une Epaisseur infErieure A 60 µm. La composition pharmaceutique se prEsente sous la forme d'une seule unitE posologique permettant d'administrer sElectivement au cOlon un agent actif ou bien son sel pharmaceutiquement acceptable ou son ester. La composition pharmaceutique comprend un noyau et un enrobage. Le noyau renferme un agent actif ou bien son sel pharmaceutiquement acceptable ou son ester. L'enrobage comporte une couche d'un copolymEre anionique d'acide mEthacrylique et d'ester mEthylique mEthacrylique, dans lequel le rapport groupe carboxyle libre-groupe ester est d'environ 1:2. Les agents actifs pouvant Etre utilisEs sont notamment la prednisolone, l'indomEtacine, l'ibuprofEne, la mEsalazine et analogue.
PCT/IB2004/001041 2003-04-04 2004-04-05 Compositions pharmaceutiques pour liberation specifique dans le colon WO2004087113A1 (fr)

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IN568/DEL/2003 2003-04-04

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011045775A1 (fr) * 2009-10-16 2011-04-21 Ranbaxy Laboratories Limited Composition pharmaceutique à libération retardée de mésalamine
US8580302B2 (en) 2000-11-20 2013-11-12 Warner Chilcott Company, Llc Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures
EP3662895A1 (fr) 2018-12-07 2020-06-10 Tillotts Pharma AG Procédé de fabrication de noyaux de comprimés réduisant le 5-asa sans sucre
CN114224850A (zh) * 2022-02-21 2022-03-25 北京罗诺强施医药技术研发中心有限公司 固体药物组合物及其制法和药物制剂

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Publication number Priority date Publication date Assignee Title
WO1989008448A1 (fr) * 1988-03-10 1989-09-21 Nycomed As Granules spheroidaux keratinises
WO2001066094A1 (fr) * 2000-03-07 2001-09-13 Pharmatec International S.R.L. Formes pharmaceutiques solides a liberation progressive administrees par voie orale contenant de la mesalazine en tant que principe actif
US20020098235A1 (en) * 2000-11-20 2002-07-25 Dittmar Gregory Paul Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
WO1989008448A1 (fr) * 1988-03-10 1989-09-21 Nycomed As Granules spheroidaux keratinises
WO2001066094A1 (fr) * 2000-03-07 2001-09-13 Pharmatec International S.R.L. Formes pharmaceutiques solides a liberation progressive administrees par voie orale contenant de la mesalazine en tant que principe actif
US20020098235A1 (en) * 2000-11-20 2002-07-25 Dittmar Gregory Paul Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SANGEKAR S A ET AL: "Comparative scintigraphic evaluation of aromatic-azo polymers and Eudragit((R)) S-100 for colonic release in beagles", PROCEEDINGS OF THE CONTROLLED RELEASE SOCIETY 1994 UNITED STATES, no. 21, 1994, pages 330 - 331, XP009035217, ISSN: 1076-0458 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8580302B2 (en) 2000-11-20 2013-11-12 Warner Chilcott Company, Llc Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures
US9089492B2 (en) 2000-11-20 2015-07-28 Warner Chilcott Company, Llc Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures
WO2011045775A1 (fr) * 2009-10-16 2011-04-21 Ranbaxy Laboratories Limited Composition pharmaceutique à libération retardée de mésalamine
US20120282333A1 (en) * 2009-10-16 2012-11-08 Ranbaxy Laboratories Limited Delayed release pharmaceutical composition of mesalamine
US9463163B2 (en) 2009-10-16 2016-10-11 Sun Pharmaceutical Industries Limited Delayed release pharmaceutical composition of mesalamine
EP3662895A1 (fr) 2018-12-07 2020-06-10 Tillotts Pharma AG Procédé de fabrication de noyaux de comprimés réduisant le 5-asa sans sucre
WO2020115258A1 (fr) 2018-12-07 2020-06-11 Tillotts Pharma Ag Procédé de fabrication de cœurs de comprimés 5-asa sans sucre réducteur
CN114224850A (zh) * 2022-02-21 2022-03-25 北京罗诺强施医药技术研发中心有限公司 固体药物组合物及其制法和药物制剂

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