WO1987006130A1 - Matrix type tablets - Google Patents
Matrix type tablets Download PDFInfo
- Publication number
- WO1987006130A1 WO1987006130A1 PCT/FR1987/000121 FR8700121W WO8706130A1 WO 1987006130 A1 WO1987006130 A1 WO 1987006130A1 FR 8700121 W FR8700121 W FR 8700121W WO 8706130 A1 WO8706130 A1 WO 8706130A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- matrix
- tablets
- active principle
- buffer substances
- tablets according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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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
- A61K9/2009—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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
Definitions
- the present invention relates to extended-type matrix tablets which comprise one or more active ingredients and one or more buffer substances.
- matrix tablets prepared by mixing the active principle with waxes, water-insoluble materials, such as hydrophobic polymers, or polymers forming gels then compression of the mixture.
- microcapsules obtained by coating particles of active ingredient, for example, with ethylcellulose or acrylic polymers.
- acid drugs mention may be made of diclofenac, antibiotics (for example penicillins, cephalosporins).
- the present invention applies more particularly to basic drugs.
- the buffer substances used according to the present invention are physiologically acceptable compounds. It is possible in particular to use citric acid, tartic acid, boric acid or their salts, primary, secondary or tertiary phosphates (for example sodium or potassium phosphates), amino acids, such as glycine, or their salts, ammonium chloride, potassium chloride, sodium acetate or a mixture of these compounds. These compounds can also be used in the form of hydrates.
- the matrix tablets of the present invention can be prepared according to the conventional method by mixing the active ingredient and the buffer substances in the constituent of the matrix and then compressing the mixture.
- excipients such as lactose, sucrose, mannitol, starches and lubricants such as magnesium stearate.
- the constituents of the matrix can be chosen, for example, from waxes (caraauba wax, beeswax, lanolin, hydrogenated soybean oil, hydrogenated castor oil, hydrogenated beef tallow, higher alcohols, paraffins) (for example, ethylcellulose), gel-forming polymers (for example, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, polysaccharides, agar, collagen).
- the buffer content is the amount that maintains the buffer for the duration of the drug release from the tablets.
- the ratio of the amount of buffer substances to the amount of active ingredient in the tablets depends on the diffusion rates of these two types of constituents.
- the desired result is obtained by using 1 to 10 parts by weight (preferably 1 to 5 parts by weight) of substances. buffer for 1 part by weight of active ingredient.
- the amount of the constituents of the matrix is not very precise. It can be determined, for example, based on the amounts and properties of the buffer substances and drugs used or the desired release time.
- tablets were prepared, having the following composition, for one tablet:
- metoclopramide base 15.6 mg citric acid, monohydrate 26 mg
- metoclopramide base 15.6 mg disodium phosphate, anhydrous 26 mg
- metoclopramide base 15.6 mg paraffin 130 mg lactose 104 mg magnesium stearate 10.4 mg
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
COMPRIMES A MATRICE MATRIX TABLETS
La présente invention concerne des comprimés de type matrice, à diffusion prolongée, qui comprennent un ou plusieurs principes actifs et une ou plusieurs substances tampon.The present invention relates to extended-type matrix tablets which comprise one or more active ingredients and one or more buffer substances.
Au cours des recherches pour la mise au point de médicaments à libération prolongée, on a déjà étudié des comprimés à matrice, préparés par mélange du principe actif avec des cires, des matériaux insolubles dans l'eau, tels les polymères hydrophobes, ou des polymères formant des gels puis compression du mélange.In the course of research for the development of sustained-release medicaments, matrix tablets have already been studied, prepared by mixing the active principle with waxes, water-insoluble materials, such as hydrophobic polymers, or polymers forming gels then compression of the mixture.
On a égalemant étudié des microcapsules, obtenues par enrobage de particules de principe actif, par exemple, par l'éthylcellulose ou les polymères acryliques.We also studied microcapsules, obtained by coating particles of active ingredient, for example, with ethylcellulose or acrylic polymers.
Cependant, bien que l'effet de libération prolongée soit obtenu avec les comprimés à matrice de type classique, la vitesse de dissolution du médicament dépend de sa solubilité dans les liquides digestifs ce qui pose un problème dans le cas d'un médicament basique puisque sa vitesse de dissolution augmente dans le liquide gastrique mais diminue dans le liquide intestinal.However, although the prolonged release effect is obtained with conventional matrix tablets, the speed of dissolution of the drug depends on its solubility in digestive fluids which poses a problem in the case of a basic drug since its dissolution rate increases in the gastric fluid but decreases in the intestinal fluid.
De plus, la cinétique de dissolution du médicament à partir de médicaments à matrice étant d'ordre 1, la quantité dissoute décroît avec le temps.In addition, the kinetics of dissolution of the drug from matrix drugs being of order 1, the dissolved amount decreases over time.
Dans l'intestin qui est une importante zone d'absorption des médicaments, la dissolution des comprimés à matrice est donc considérablement réduite, en particulier dans le cas des médicaments basiques, ce qui peut diminuer la durée d'action du médicament.In the intestine, which is an important absorption area for drugs, the dissolution of matrix tablets is therefore considerably reduced, especially in the case of basic drugs, which can decrease the duration of action of the drug.
D'autre part, dans le cas d'un médicament acide, la vitesse de dissolution diminue dans le liquide gastrique alors qu'elle augmente dans le liquide intestinal.On the other hand, in the case of an acidic drug, the rate of dissolution decreases in the gastric fluid while it increases in the intestinal fluid.
Un médicament acide étant difficilement dissous dans l'estomac, il peut donc arriver que son effet tarde à se manifester, en particulier dans le cas où il est absorbé après un repas et reste longtemps dans l'estomac. On a donc cherché une solution aux problèmes décrits ci-dessus, ce qui conduit à la découverte des comprimés à matrice de la présente invention.An acidic drug is difficult to dissolve in the stomach, so it can happen that its effect is slow to manifest, especially in the case where it is absorbed after a meal and remains for a long time in the stomach. We therefore sought a solution to the problems described above, which leads to the discovery of the matrix tablets of the present invention.
On a trouvé que, dans les comprimés à matrice contenant une substance tampon, cette substance bien que facilement dissoute, était retenue pendant longtemps dans les pores de la matrice, assurant ainsi un pH constant dans les pores.It has been found that in matrix tablets containing a buffer substance, this substance, although easily dissolved, is retained for a long time in the pores of the matrix, thus ensuring a constant pH in the pores.
On en a donc déduit qu'il était possible de dissoudre un médicament de façon continue et indépendante du pH du liquide digestif et aussi que l'on pouvait faire varier à volonté la vitesse de dissolution du médicament, en modifiant la composition du milieu tampon.It was therefore deduced therefrom that it was possible to dissolve a medicament continuously and independently of the pH of the digestive liquid and also that the speed of dissolution of the medicament could be varied at will, by modifying the composition of the buffer medium.
A titre d'exemples de médicaments basiques qui peuvent être utilisés selon la présente invention, on peut citer le métoclopramidë, le sulpiride, le metoprolol, le tiapride, la zotepine, la cibenzoline, la cimetidine, la clnnarizlne, l' ephedrlne, l'atropine, la pyridoxlne et la codéine.As examples of basic drugs which can be used according to the present invention, mention may be made of metoclopramide, sulpiride, metoprolol, tiapride, zotepine, cibenzoline, cimetidine, clnnarizlne, ephedrlne, atropine, pyridoxlne and codeine.
A titre d'exemples de médicaments acides, on peut citer le diclofenac, les antibiotiques (par exemple pénicillines, cephalosporines).As examples of acid drugs, mention may be made of diclofenac, antibiotics (for example penicillins, cephalosporins).
La présente invention s'applique plus particulièrement aux médicaments basiques.The present invention applies more particularly to basic drugs.
Les substances tampon utilisées selon la présente invention sont des composés physiologiquement acceptables. On peut utiliser en particulier l'acide citrique, l'acide tartique, l'acide borique ou leurs sels, les phosphates primaire, secondaire ou tertiaire (par exemple phosphates de sodium ou de potassium), les acides aminés, comme la glycine, ou leurs sels, le chlorure d'ammonium, le chlorure de potassium, l'acétate de sodium ou un mélange de ces composés. On peut également utilisé ces composés sous forme d'hydrates.The buffer substances used according to the present invention are physiologically acceptable compounds. It is possible in particular to use citric acid, tartic acid, boric acid or their salts, primary, secondary or tertiary phosphates (for example sodium or potassium phosphates), amino acids, such as glycine, or their salts, ammonium chloride, potassium chloride, sodium acetate or a mixture of these compounds. These compounds can also be used in the form of hydrates.
Les comprimés à matrice de la présente invention peuvent être préparés selon le procédé classique en mélangeant le principe actif et les substances tampon dans le constituant de la matrice puis en comprimant le mélange.The matrix tablets of the present invention can be prepared according to the conventional method by mixing the active ingredient and the buffer substances in the constituent of the matrix and then compressing the mixture.
On peut également utiliser des excipients tels que lactose, sucrose, mannitol, amidons et des lubrifiants tels que le stéarate de magnésium. Les constituants de la matrice peuvent être choisis par exemple, parmi les cires (cire de caraauba, cire d'abeille, lanoline, huile de soja hydrogénée, huile de ricin hydrogénée, suif de boeuf hydrogéné, alcools supérieurs, paraffines), les polymères hydrophobes (par exemple, l'éthylcellulose), les polymères formant des gels (par exemple, carboxyméthylcellulose, polyvinylpyrrolidone, hydroxypropylméthylcellulose, polysaccarides, agar, collagène).It is also possible to use excipients such as lactose, sucrose, mannitol, starches and lubricants such as magnesium stearate. The constituents of the matrix can be chosen, for example, from waxes (caraauba wax, beeswax, lanolin, hydrogenated soybean oil, hydrogenated castor oil, hydrogenated beef tallow, higher alcohols, paraffins) (for example, ethylcellulose), gel-forming polymers (for example, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, polysaccharides, agar, collagen).
Pour préparer les comprimés de l'invention, on peut également faire fondre une cire constituant la matrice ou dissoudre un polymère dans un solvant approprié, ajouter le principe actif, les substance tampon et éventuellement des excipients, malaxer, sécher et tamiser pour obtenir des particules, puis ajouter un lubrifiant et comprimer le mélange.To prepare the tablets of the invention, it is also possible to melt a wax constituting the matrix or to dissolve a polymer in an appropriate solvent, add the active principle, the buffer substance and optionally excipients, knead, dry and sieve to obtain particles. , then add a lubricant and compress the mixture.
La teneur en substances tampon correspond à la quantité qui permet de maintenir l'effet tampon pendant toute le durée de libération du médicament à partir des comprimés.The buffer content is the amount that maintains the buffer for the duration of the drug release from the tablets.
De plus, le rapport de la quantité de substances tampon à la quantité de principe actif dans les comprimés dépend des vitesses de diffusion de ces deux types de constituants.In addition, the ratio of the amount of buffer substances to the amount of active ingredient in the tablets depends on the diffusion rates of these two types of constituents.
On peut donc déterminer la quantité de substance tampon nécessaire d'après la quantité de principe actif et ses propriétés mais en général, on obtient le résultat désiré en utilisant 1 à 10 parties en poids (de préférence 1 à 5 parties en poids) de substances tampon pour 1 partie en poids de principe actif.It is therefore possible to determine the quantity of buffer substance necessary according to the quantity of active principle and its properties, but in general, the desired result is obtained by using 1 to 10 parts by weight (preferably 1 to 5 parts by weight) of substances. buffer for 1 part by weight of active ingredient.
La quantité des constituants de la matrice n'est pas très précise. Elle peut être déterminée par exemple, d'après les quantités et les propriétés des substances tampon et des médicaments utilisés ou du temps de libération souhaité.The amount of the constituents of the matrix is not very precise. It can be determined, for example, based on the amounts and properties of the buffer substances and drugs used or the desired release time.
On choisit en général une quantité correspondant à 20-80 %, de préférence 40-60 % , du poids du comprimé. Selon la méthode décrite précédemment, on a préparé des comprimés ayant la composition suivantes, pour un comprimé :In general, an amount corresponding to 20-80%, preferably 40-60%, of the weight of the tablet is chosen. According to the method described above, tablets were prepared, having the following composition, for one tablet:
Exemple 1 :Example 1:
metoclopramide base 15,6 mg acide citrique, monohydrate 26 mgmetoclopramide base 15.6 mg citric acid, monohydrate 26 mg
(substance tampon) paraffine 130 mg lactose 78 mg stéarate de magnésium 10,4 mg(buffer substance) paraffin 130 mg lactose 78 mg magnesium stearate 10.4 mg
260 mg260 mg
Exemple 2 :Example 2:
metoclopramide, base 15,6 mg acide citrique, monohydrate 13 mgmetoclopramide, base 15.6 mg citric acid, monohydrate 13 mg
(substance tampon) phosphate disodique, anhydre 13 mg(buffer substance) disodium phosphate, anhydrous 13 mg
(substance tampon) paraffine 130 mg lactose 78 mg stéarate de magnésium 10,4 mg(buffer substance) paraffin 130 mg lactose 78 mg magnesium stearate 10.4 mg
260 mg260 mg
Exemple 3 :Example 3:
metoclopramide base 15,6 mg phosphate disodique, anhydre 26 mgmetoclopramide base 15.6 mg disodium phosphate, anhydrous 26 mg
(substance tampon) phosphate dipotasslque, anhydre 26 mg(buffer substance) phosphate dipotassium, anhydrous 26 mg
(substance tampon) paraffine 130 mg lactose 52 mg stéarate de magnésium 10,4 mg(buffer substance) paraffin 130 mg lactose 52 mg magnesium stearate 10.4 mg
260 mg Composition de référence260 mg Reference composition
metoclopramide base 15,6 mg paraffine 130 mg lactose 104 mg stéarate de magnésium 10,4 mgmetoclopramide base 15.6 mg paraffin 130 mg lactose 104 mg magnesium stearate 10.4 mg
260 mg260 mg
La vitsse de libération du principe actif dans des liquides gastrique et intestinal artificiels a été étudiée selon la méthode décrite dans la pharmacopée japonaise, 10eme édition (méthode Paddle) .The speed of release of the active ingredient in artificial gastric and intestinal fluids was studied according to the method described in the Japanese Pharmacopoeia, 10th edition (Paddle method).
- Essai de dissolution 1 : conditions : 900 ml de liquide (pH - 1,2), 37°C, 100 r.p.m.- Dissolution test 1: conditions: 900 ml of liquid (pH - 1.2), 37 ° C, 100 r.p.m.
- Essai de dissolution 2 : conditions : 900 ml de liquide (pH = 6,8), 37ºC, 100 r.p.m.- Dissolution test 2: conditions: 900 ml of liquid (pH = 6.8), 37ºC, 100 r.p.m.
Par ces méthodes, on a étudié la vitesse de dissolution des comprimés suivants :By these methods, the speed of dissolution of the following tablets was studied:
A : comprimé de l'exemple 1.A: tablet of Example 1.
B : comprimé de l'exemple 2.B: tablet of Example 2.
C : comprimé de l'exemple 3.C: tablet of Example 3.
D : comprimé de référence. D: reference tablet.
Les résultats suivants ont été obtenus :The following results were obtained:
D'après les résultats obtenus, il apparaît que l'on obtient, avec les comprimés à matrice de la présente invention, une libération prolongée du principe actif qui est indépendante du pH du milieu de dissolution contrairement à la libération à partir de comprimés ne contenant pas de substance tampon (essai de dissolution D) . Il apparaît également que l'on peut contrôler la vitesse de libération du principe actif en changeant la nature et/ou les proportions des substances tampon. From the results obtained, it appears that one obtains, with the matrix tablets of the present invention, a prolonged release of the active principle which is independent of the pH of the dissolution medium unlike the release from tablets not containing no buffer substance (dissolution test D). It also appears that the speed of release of the active principle can be controlled by changing the nature and / or the proportions of the buffer substances.
Claims
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61/87374 | 1986-04-16 | ||
| JP61087374A JPH0776172B2 (en) | 1986-04-16 | 1986-04-16 | Matrice locks |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1987006130A1 true WO1987006130A1 (en) | 1987-10-22 |
Family
ID=13913118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FR1987/000121 Ceased WO1987006130A1 (en) | 1986-04-16 | 1987-04-14 | Matrix type tablets |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPH0776172B2 (en) |
| AU (1) | AU7284087A (en) |
| WO (1) | WO1987006130A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0322392A1 (en) * | 1987-12-22 | 1989-06-28 | Pharmacia Ab | Oral dosage units for pharmaceuticals and their use and preparation |
| WO1990006107A1 (en) * | 1988-11-30 | 1990-06-14 | Schering Corporation | Sustained release diltiazem formulation |
| FR2762213A1 (en) * | 1997-04-18 | 1998-10-23 | Synthelabo | PHARMACEUTICAL COMPOSITION WITH GASTRIC RETENTION |
| US6242003B1 (en) | 2000-04-13 | 2001-06-05 | Novartis Ag | Organic compounds |
| WO2009008487A1 (en) * | 2007-07-12 | 2009-01-15 | Takeda Pharmaceutical Company Limited | Coated preparation |
| US8303987B2 (en) | 2001-04-11 | 2012-11-06 | Novartis Ag | Pharmaceutical compositions comprising fluvastatin |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU682764B2 (en) * | 1994-04-01 | 1997-10-16 | Tsumura & Co. | Process for producing sustained-release tablets and enteric tablets |
| FR2745500B1 (en) * | 1996-03-04 | 1998-04-03 | Synthelabo | SUSTAINED RELEASE PHARMACEUTICAL FORMULATIONS CONTAINING MIZOLASTINE |
| GB0001315D0 (en) * | 2000-01-20 | 2000-03-08 | Novartis Ag | Organic compounds |
| CN1299678C (en) * | 2005-07-15 | 2007-02-14 | 任巧玲 | Sulpride dispersion tablets prepn. method |
| JP6123795B2 (en) * | 2012-03-30 | 2017-05-10 | アステラス製薬株式会社 | Controlled release pharmaceutical composition |
| JP6728425B2 (en) * | 2019-02-28 | 2020-07-22 | アナプラシ ファーマシューティカルズ エルエルシー | Cream, lotion or gel composition for treating psoriasis |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB997914A (en) * | 1962-07-31 | 1965-07-14 | Neisler Lab Inc | Pharmaceutical compositions |
| FR2150931A1 (en) * | 1971-09-04 | 1973-04-13 | Beecham Group Ltd | |
| FR2223047A1 (en) * | 1973-03-28 | 1974-10-25 | Benzon As Alfred | |
| GB2025227A (en) * | 1978-07-15 | 1980-01-23 | Boehringer Sohn Ingelheim | Pharmaceutical preparations in retard form |
| EP0121901A1 (en) * | 1983-04-08 | 1984-10-17 | Boehringer Ingelheim Pharmaceuticals Inc. | pH independent controlled releasable tablets |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2831164A1 (en) * | 1978-07-15 | 1980-01-24 | Boehringer Sohn Ingelheim | Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer |
| FR2444460A1 (en) * | 1978-12-22 | 1980-07-18 | Panoz Donald | Controlled release oral galenical formulation - contains active components in micro-granules prepd. under high compression |
| JPS58105914A (en) * | 1981-12-17 | 1983-06-24 | Lion Corp | Antacid having sustained activity |
| US4421736A (en) * | 1982-05-20 | 1983-12-20 | Merrel Dow Pharmaceuticals Inc. | Sustained release diethylpropion compositions |
| US4704284A (en) * | 1982-08-12 | 1987-11-03 | Pfizer Inc. | Long-acting matrix tablet formulations |
| DK151608C (en) * | 1982-08-13 | 1988-06-20 | Benzon As Alfred | PROCEDURE FOR PREPARING A PHARMACEUTICAL PERORAL POLYDEPOT PREPARATION WITH CONTROLLED RELEASE |
-
1986
- 1986-04-16 JP JP61087374A patent/JPH0776172B2/en not_active Expired - Lifetime
-
1987
- 1987-04-14 WO PCT/FR1987/000121 patent/WO1987006130A1/en not_active Ceased
- 1987-04-14 AU AU72840/87A patent/AU7284087A/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB997914A (en) * | 1962-07-31 | 1965-07-14 | Neisler Lab Inc | Pharmaceutical compositions |
| FR2150931A1 (en) * | 1971-09-04 | 1973-04-13 | Beecham Group Ltd | |
| FR2223047A1 (en) * | 1973-03-28 | 1974-10-25 | Benzon As Alfred | |
| GB2025227A (en) * | 1978-07-15 | 1980-01-23 | Boehringer Sohn Ingelheim | Pharmaceutical preparations in retard form |
| EP0121901A1 (en) * | 1983-04-08 | 1984-10-17 | Boehringer Ingelheim Pharmaceuticals Inc. | pH independent controlled releasable tablets |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0322392A1 (en) * | 1987-12-22 | 1989-06-28 | Pharmacia Ab | Oral dosage units for pharmaceuticals and their use and preparation |
| WO1989005630A1 (en) * | 1987-12-22 | 1989-06-29 | Pharmacia Ab | Oral dosage units for pharmaceuticals and their use and preparation |
| WO1990006107A1 (en) * | 1988-11-30 | 1990-06-14 | Schering Corporation | Sustained release diltiazem formulation |
| EP0373417A1 (en) * | 1988-11-30 | 1990-06-20 | Schering Corporation | Sustained release diltiazem formulation |
| FR2762213A1 (en) * | 1997-04-18 | 1998-10-23 | Synthelabo | PHARMACEUTICAL COMPOSITION WITH GASTRIC RETENTION |
| WO1998047506A1 (en) * | 1997-04-18 | 1998-10-29 | Sanofi-Synthelabo | Gastric-retained pharmaceutical composition |
| AU737634B2 (en) * | 1997-04-18 | 2001-08-23 | Sanofi-Synthelabo | Pharmaceutical composition for gastric residence |
| US6242003B1 (en) | 2000-04-13 | 2001-06-05 | Novartis Ag | Organic compounds |
| US6432447B2 (en) | 2000-04-13 | 2002-08-13 | Novartis Ag | Organic compounds |
| US8303987B2 (en) | 2001-04-11 | 2012-11-06 | Novartis Ag | Pharmaceutical compositions comprising fluvastatin |
| WO2009008487A1 (en) * | 2007-07-12 | 2009-01-15 | Takeda Pharmaceutical Company Limited | Coated preparation |
| US9427434B2 (en) | 2007-07-12 | 2016-08-30 | Takeda Pharmaceutical Company Limited | Coated preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62242615A (en) | 1987-10-23 |
| AU7284087A (en) | 1987-11-09 |
| JPH0776172B2 (en) | 1995-08-16 |
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