IE51549B1 - Solid medicament formulations containing nifedipine,and processes for their preparation - Google Patents
Solid medicament formulations containing nifedipine,and processes for their preparationInfo
- Publication number
- IE51549B1 IE51549B1 IE2075/81A IE207581A IE51549B1 IE 51549 B1 IE51549 B1 IE 51549B1 IE 2075/81 A IE2075/81 A IE 2075/81A IE 207581 A IE207581 A IE 207581A IE 51549 B1 IE51549 B1 IE 51549B1
- Authority
- IE
- Ireland
- Prior art keywords
- nifedipine
- surface area
- solid
- specific surface
- medicament
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
1. A solid pharmaceutical composition containing as the active ingredient nifedipine crystals with a specific surface area of 0,5 to 6 m**2 /g, in admixture with a solid diluent.
Description
The present invention relates to novel particular solid medicament formulations containing the known compound nifedipine, which has an action on the circulation, and to processes for their production.
It has already been disclosed that the compound nifedipine has very powerful actions which influence the circulation (see Eritish Patent Specification 1,173,862). Because nifedipine is sensitive to light and sparingly soluble, a number of difficulties occur in the galenical formulation of medieamenta! specialities, as is seen from numerous patents and patent applications for- special formulations of this active compound. Thus, for example, U.S. Patent Specification 3,784,684 relates to particular gelatin capsules for chewing which contain nifedipine and as a result of which the coronary action of nifedipine can be. advantageously utilised. Furthermore, British Patent Specification 1,456,618 describes and claims solid medicament formulations which likewise ensure a good bioavailability of nifedipine. Solid medicament forms in which the poor solubility of nifedipine is said to be compensated by using certain solubilising agents and surface-active substances are also described in DT-OS (German Published Specification) 2,822,882. The ease of absorption of nifedipine as a result of using polyethylene glycol and certain porous excipient substances is also said to be improved in European Published Patent Application 1,247.
All previous attempts to compensate the poor solubility of nifedipine by certain measures and at the same time to ensure good bio-availability have a number of disadvantages. The use of surface-active substances, solubilising agents and certain excipient substances which have a particular surface, for example are porous, frequently leads to administration forms in which the preparations are undesirably large in size. In order to facilitate swallowing, such tablets or capsules are frequently converted into particular shapes, - s.uch as, ellipsoids or elongate shapes, but this no longer leads to satisfactory results in the case of preparations weighing over 400 mg. More frequent intake of smaller preparations also does not provide a satisfactory solution.
For medicament formulations, both the number and the amount of auxiliaries and excipients should be kept as low as possible. On comparison of two medicamentous specialities, that preparation which, in addition to the active compound, contains as few auxiliaries and additives as possible is always preferred, in order largely to avoid undesired biological actions.
A further disadvantage of the nifedipine-containing preparations which have been known hitherto is the expensive process for producing them, this disadvantage applying, in particular, to liquid formulations and capsule preparations. The high sensitivity of nifedipine to light and its poor solubility result in expensive process measures which, especially in the case of liquid formulations, require, as protection from light, exclusion of daylight and the use of sodium light.
According to the present invention we provide a solid pharmaceutical composition containing as the active ingredient nifedipine crystals with a specific surface p area of 0.5 to 6 m /g, in admixture with a solid diluent.
The invention also provides a solid medicament in dosage unit form comprising nifedipine crystals with a specific surface area of 0.5 to 6m /g.
The invention also provides a medicament in the form of tablets (including lozenges and granules), dragees, capsules, pills, sachet or multiphase preparations, such as two-layer tablets comprising nifedipine crystals with a specific surface area of 0.5 to 6m /g.
Medicament as used in this Specification means physically discrete coherent portions suitable for medical .administration. Medicament in dosage unit form as used in this Specification means physically discrete coherent units suitable for medical administration 51548 each containing a daily dose or a multiple (up tn four times) or submultiple (down to a fortieth) of a daily dose of the compound of the invention in association with a carrier and/or enclosed within an envelope.
Whether the medicament contains a daily dose or, for example, a half, a third or a quarter of a daily dose will depend on whether the medicament is to be administered once or, for example, twice, three times or four times a day respectively.
The diluents to be used in pharmaceutical compositions (e.g. granulates) adapted to be formed into tablets, dragees, capsules and pills include the following: (a) fillers and extenders, e.g. starch, sugars, mannitol, and silicic acid; (b) binding agents, e.g. carboxymethyl cellulose and other cellulose derivatives, alginates, gelatine and polyvinyl pyrrolidone; (c) moisturizing agents, e.g. glycerol; (d) disintegrating agents, e.g. agar-agar, calcium carbonate and sodium bicarbonate; (e) agents for retarding dissolution e.g. paraffin; (f) resorption accelerators, e.g. quaternary ammonium compounds; (g) surface active agents, e.g. cetyl alcohol, glycerol monostearate; (h) adsorptive carriers, e.g. kaolin and bentonite; (i) lubricants, e.g. talc, calcium and magnesium stearate and solid polyethyl glycols.
The tablets, dragees, capsules and pills formed from the pharmaceutical compositions of the invention can have the customary coatings, envelopes and protective matrices, which may contain opacifiers. They can be so constituted that they release the active ingredient only or preferably in a particular part of the intestinal tract, possibly over a period of time. The coatings, envelopes and protective matrices may be made, for example, of polymeric substances or waxes.
The ingredient can also be made up in microencapsulated form together with one or several of the above-mentioned diluents.
Pharmaceutical compositions according to the invention can also contain colouring agents and preservatives as well as perfumes and flavouring additions (e.g. peppermint oil and eucalyptus oil) and sweetening agents (e.g. saccharin).
In addition to the nifedipine crystals of stated surface are, the pharmaceutical compositions' and medicaments according to the invention can also contain other pharmaceutically active compounds.
Any diluent in the medicaments of the present invention may be any of those mentioned above in relation to the pharmaceutical compositions of the present invention.
The discrete coherent portions constituting the medicament according to the invention will generally be adapted by virtue of their shape or packaging for medical administration and may be, for example, any of the following: tablets (including lozenges and granulates), pills, dragees, capsules, sachets and multiphase preparations, such as two-layer tablets. Some of these forms may be made up for delayed release of the active ingredient. Some, such as capsules, include a protective envelope which renders the portions of the medicament physically discrete and coherent.
Those solid medicaments and pharmaceutical compositions which contain nifedipine crystals with a specific surface area of 1 to 4 m /g are particularly advantageous.
The nifedipine crystals which have a specific surface p area of 0.5 to 6 m /g and are used according to the invention are prepared by grinding the crystal mixtures obtained from the synthesis of nifedipine. Grinding can be effected, for example, with pin disc mills or hammer mills.
Nifedipine with the. desired surface area can be obtained by varying the speed of the mill, the amount of product fed in and/or the grinding period.
If a product with a relatively high specific 2 surface area (for example 5 m /g) is desired, it is advantageous to carry out grinding with air jet mills.
Crystals with a lower specific surface area (for example 2 0.5 m /g) are advantageously to be prepared by sieving in very fine sieves, preferably with mesh widths of 0.1 to 0.2 mm. In all cases, it is also possible, to obtain a product with the desired specific surface area by mixing nifedipine crystals of different specific surface areas.
Accordingly the present invention also provides a process for the production of pharmaceutic compositions of the present invention in which nifedipine crystals obtained from the synthesis are converted in a crystal mixture with o a specific surface area of 0.5 to 6 m /g by grinding or sieving and the solid pharmaceutical compositions are formulated from these nifedipine crystals using one or more solid auxiliaries and/or excipients.
The specific surface area is measured by the gas adsorption method (BET method; see S. Brunauer: The Adsorption of Gases and Vapours, Princeton (19^5))· Surprisingly, the solid-formulations according to the invention have an unexpectedly high bio-availability.
In the publication by I. Sugimoto et al, Drug Development and Industrial Pharmacy, 6(2), 137-160 (1980), it is particularly emphasised (see page 139) that, when administered orally, crystalline nifedipine is poorly absorbed and has only a very low bio-availability. It could thus not be expected that, after oral administration of the formulation according to the invention, which contains crystalline nifedipine, the plasma concentration rises rapidly and remains at a high value for many hours. In cases in which nifedipine must be taken over relatively long periods, it is sufficient, on the basis of this, very high period of action, to administer 1 or 2 tablets daily. Another considerable advantage is that very small tablets with a high content of active .compound can be prepared, since solubilising agents, surface-active substances and and additional auxiliaries ean largely be dispensed with.
The smallness of the tablets and the surprisingly long period of action of the formulation according to the invention enable nifedipine to be used for the treatment of coronary illnesses over relatively long periods, and also prophylactically, and furthermore, this formulation presents the possibility of employing the lypotensive action of nifedipine for the treatment of hypertonia.
The long-lasting blood level of the active compound which is obtainable by the formulation according to the invention represents an extension of the possibilities' for using nifedipine in practice, and at the same time mean relief for the patients.
Prom the knowledge of the state of the art, from which it can be seen that the experts have for years been concerned with finding useful formulation forms for the active compound nifedipine, which is difficult to formulate, it is to be described as exceptionally surprising that a very simple and effective principle for galenical processing has been found by choosing a quite definite specific surface area of the active compound.
The solid formulation forms according to the invention represent relief for the patient during administration, and at the same time increase the reliability of the patient's treatment.
To demonstrate the advantageous action of the medicament formulations according to the invention, the plasma concentration of each of 8 persons was determined for several hours after the administration. The values can be seen from the following table: Table Time (hours.) 1 . . · 2. . . 3 - .4.. . . .6.....8. . . 10.- 25—5 Plasma concentration, ug/l after peroral administration of the 105.8 86.1 65.3 63-9 43.1 46.7 11.8 10.8 tablets from Example 1 (20 mg) ditto, after peroral administration of the tablets 52.1 66.3 60.4 51-3 32.4 25 18.8 11.4 from Example 2 (20 mg) The following Examples illustrate processes for the production of solid medicament formulations according to the invention.
Example 1 200 g of nifedipine crystals with a specific surface area of 4 m /g were mixed with 348 g of microcrystalline cellulose, 100 g of lactose, 10 g of Tween 80, (Trade Mark), 70 g of starch and 2 g of magnesium stearate. A paste was prepared from a further 70 g of starch with water and, in the customary’manner, the paste-was granulated with the abovementioned mixture and the mixture was dried and then pressed to tablets which individually weighed 80mg. These tablets were then labelled; they had a diameter of 6 mm.
A suspension of 18 g of hydroxypropylmethylcellulose, 6 g of polyethylene glycol, 5.4 g of titanium dioxide, 0.6 g of iron oxide and 370 g of water or ethanol was used to lacquer 800 g of tablets.
Example 2 200 g of nifedipine crystals with a specific p surface area or I m /g were pressed to 80 mg tablets with a diameter of 6 mm and filmcoated analogously to Example 1. 51548 Example 3 200 g of nifedipine with a specific surface area of 1.2 m2/g were mixed with 800 g of lactose, 960 g of starch and 40 g of magnesium stearate. 100 mg portions of the mixture were filled into size 3 hard gelatin capsules. Each capsule then contained 10 mg of nifedipine. Capsules containing various dosages, for example between 5 mg and 40 mg of active compound per capsule, could be prepared by varying the capsule size and the weight of contents.
Example 4 Two-layer tablets were prepared. One layer consisted of 7.5 mg of nifedipine with a specific surface ο area of 6 m /g, 7.5 mg of lactose, 30 mg of starch, 3 mg of polyvinylpyrrolidone and 2 mg of magnesium stearate (100 mg in total), and the second layer had the same composition, but the nifedipine had a specific surface area of 0.6 m /g. The compressed two-layer tablets weighing a total of 200 mg could be provided with a break20 ing groove in order to provide an individual dosage for the patient. 51548
Claims (7)
1. CLAIMS:1. A solid pharmaceutical composition containing as the active ingredient nifedipine crystals with a specific 2 surface area of 0.5 to 6 m /g, in admixture with a solid 5 diluent.
2. A solid medicament in dosage unit form comprising nifedipine crystals with a specific surface area of 0.5 to 6 m /g.
3. A medicament in the form of tablets, pills, 10 dragees, capsules, suppositories, sachets or two-layer tablets comprising nifedipine crystals with a specific surface area of 0.5 to 6 m- /g.
4. A pharmaceutical composition according to claim 1 or medicament according to claim 2 or 3 in which the 15 nifedipine crystals have a specific surface area of 1 to 4 m 2 /g.
5. A solid medicament according to claim 3 as hereinbefore specifically mentioned in any one of Examples 1 to 4. 20 6. a process for the preparation of solid pharmaceutical composition according to claim 1, in which nifedipine crystals obtained from the synthesis are converted into a crystal mixture with a specific surface area of 0.5 to o
6. M /g by grinding or sieving, and solid pharmaceutical 25 compositions are formulated from these nifedipine crystals using one or more solid auxiliaries and/or excipients.
7. Nifedipine crystals with a specific surface area of 0.5 to 6 m /g for use in combating circulatory illnesses and hypertension. Dated this the 8th day of September, 1981.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19803033919 DE3033919A1 (en) | 1980-09-09 | 1980-09-09 | SOLID PHARMACEUTICAL PREPARATIONS CONTAINING NIFEDIPINE AND METHOD FOR THE PRODUCTION THEREOF |
Publications (2)
Publication Number | Publication Date |
---|---|
IE812075L IE812075L (en) | 1982-03-09 |
IE51549B1 true IE51549B1 (en) | 1987-01-07 |
Family
ID=6111496
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE2075/81A IE51549B1 (en) | 1980-09-09 | 1981-09-08 | Solid medicament formulations containing nifedipine,and processes for their preparation |
Country Status (20)
Country | Link |
---|---|
EP (1) | EP0047899B2 (en) |
JP (1) | JPS5914446B2 (en) |
AR (1) | AR226377A1 (en) |
AT (1) | ATE5761T1 (en) |
AU (1) | AU558331B2 (en) |
CA (1) | CA1180277A (en) |
DD (1) | DD201974A5 (en) |
DE (2) | DE3033919A1 (en) |
DK (1) | DK154326C (en) |
FI (1) | FI72648B (en) |
GR (1) | GR78237B (en) |
HU (1) | HU184879B (en) |
IE (1) | IE51549B1 (en) |
IL (1) | IL63749A (en) |
NO (1) | NO157368B (en) |
NZ (1) | NZ198285A (en) |
PH (1) | PH24097A (en) |
PL (1) | PL232951A1 (en) |
PT (1) | PT73603B (en) |
ZA (1) | ZA816213B (en) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
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US5264446A (en) * | 1980-09-09 | 1993-11-23 | Bayer Aktiengesellschaft | Solid medicament formulations containing nifedipine, and processes for their preparation |
JPS5846019A (en) * | 1981-09-14 | 1983-03-17 | Kanebo Ltd | Nifedipine preparation with prolonged action |
DE3222367A1 (en) * | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Use of 1,4-dihydropyridines in antiarteriosclerotics and preparation thereof |
JPS59101423A (en) * | 1982-12-02 | 1984-06-12 | Takada Seiyaku Kk | Novel solid pharmaceutical preparation of nifedipine |
US4529733A (en) * | 1983-04-06 | 1985-07-16 | Merrell Dow Pharmaceuticals Inc. | Antihypertensive 3-furoyl-1,4-dihydropyridines |
DE3318649A1 (en) * | 1983-05-21 | 1984-11-22 | Bayer Ag, 5090 Leverkusen | TWO-PHASE FORMULATION |
HU198844B (en) * | 1984-06-14 | 1989-12-28 | Sandoz Ag | Process for producing new galenic pharmaceutical composition ensuring retarded release of active ingredient |
IT1178511B (en) * | 1984-09-14 | 1987-09-09 | Pharmatec Spa | PROCEDURE FOR THE PREPARATION OF A SOLID FORM FOR ORAL USE BASED ON NIFEDIPINE WITH RELEASE |
IT1187751B (en) * | 1985-10-15 | 1987-12-23 | Eurand Spa | PROCEDURE FOR THE PREPARATION OF SOLID FORMULATIONS OF NIFEDIPINE WITH HIGH BIO AVAILABILITY AND WITH PROLONGED EFFECT AND FORMULATIONS SO OBTAINED |
US4940556A (en) * | 1986-01-30 | 1990-07-10 | Syntex (U.S.A.) Inc. | Method of preparing long acting formulation |
US5198226A (en) * | 1986-01-30 | 1993-03-30 | Syntex (U.S.A.) Inc. | Long acting nicardipine hydrochloride formulation |
CH673947A5 (en) * | 1986-09-23 | 1990-04-30 | Sandoz Ag | |
JPS6464659A (en) * | 1987-09-03 | 1989-03-10 | Kenbi Kogaku Kenkyusho Kk | Preparation of safe and effective powder formulation |
SE8703881D0 (en) * | 1987-10-08 | 1987-10-08 | Haessle Ab | NEW PHARMACEUTICAL PREPARATION |
DE3814532A1 (en) * | 1988-04-29 | 1989-11-09 | Bayer Ag | DHP-RETARD-PREPARATION |
JPH0298550U (en) * | 1989-01-25 | 1990-08-06 | ||
GB8903328D0 (en) * | 1989-02-14 | 1989-04-05 | Ethical Pharma Ltd | Nifedipine-containing pharmaceutical compositions and process for the preparation thereof |
US5271944A (en) * | 1991-04-05 | 1993-12-21 | Biofor, Ltd. | Pharmacologically enhanced formulations |
DE4130173A1 (en) * | 1991-09-11 | 1993-03-18 | Bayer Ag | PHARMACEUTICAL PREPARATIONS WITH A SPECIAL CRYSTAL MODIFICATION OF 1,4-DIHYDRO-2,6-DIMETHYL-4- (3-NITROPHENYL) -3,5-PYRIDINDICARBONIC ACID ISOPROPYL- (2-METHOXYETHYL) ESTER |
GB9200607D0 (en) * | 1992-01-13 | 1992-03-11 | Ethical Pharma Ltd | Pharmaceutical compositions containing nifedipine and process for the preparation thereof |
US5773025A (en) * | 1993-09-09 | 1998-06-30 | Edward Mendell Co., Inc. | Sustained release heterodisperse hydrogel systems--amorphous drugs |
US5455046A (en) * | 1993-09-09 | 1995-10-03 | Edward Mendell Co., Inc. | Sustained release heterodisperse hydrogel systems for insoluble drugs |
US6726930B1 (en) | 1993-09-09 | 2004-04-27 | Penwest Pharmaceuticals Co. | Sustained release heterodisperse hydrogel systems for insoluble drugs |
US5543099A (en) * | 1994-09-29 | 1996-08-06 | Hallmark Pharmaceutical, Inc. | Process to manufacture micronized nifedipine granules for sustained release medicaments |
ES2168351T3 (en) * | 1994-12-29 | 2002-06-16 | Shire Deutschland Gmbh & Co Kg | PHARMACEUTICAL PREPARATIONS CONTAINING NIFEDIPINE AND PROCEDURE FOR PREPARATION. |
JP3220373B2 (en) | 1995-11-28 | 2001-10-22 | バイエル薬品株式会社 | Long-acting nifedipine preparation |
US6093420A (en) | 1996-07-08 | 2000-07-25 | Edward Mendell Co., Inc. | Sustained release matrix for high-dose insoluble drugs |
IT1284604B1 (en) * | 1996-09-27 | 1998-05-21 | Roberto Valducci | CONTROLLED RELEASE PHARMACEUTICAL COMPOSITIONS FOR ORAL ADMINISTRATION CONTAINING NIFEDIPINE AS THE ACTIVE SUBSTANCE |
US6056977A (en) * | 1997-10-15 | 2000-05-02 | Edward Mendell Co., Inc. | Once-a-day controlled release sulfonylurea formulation |
JP3893058B2 (en) | 1999-09-30 | 2007-03-14 | ペンウェスト ファーマシューティカルズ カンパニー | Sustained release matrix system for highly soluble drugs |
EP1737847B1 (en) | 2004-07-30 | 2008-06-04 | Torrent Pharmaceuticals Ltd | Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol |
DE102004062475A1 (en) * | 2004-12-24 | 2006-07-06 | Bayer Healthcare Ag | Solid, orally administrable, modified release pharmaceutical dosage forms |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3330727A (en) * | 1960-04-19 | 1967-07-11 | Glaxo Lab Ltd | Griseofulvin with high specific surface area |
US3401221A (en) * | 1964-08-25 | 1968-09-10 | Norwich Pharma Co | Treatment of urinary tract infection |
DE2348334C2 (en) * | 1973-09-26 | 1982-11-11 | Boehringer Mannheim Gmbh, 6800 Mannheim | New form of preparation of N-4- [2- (5-chloro-2-methoxybenzamido) ethyl] -phenyl-sulfonyl-N'-cyclohexylurea |
DE2400819C2 (en) * | 1974-01-09 | 1982-04-22 | Bayer Ag, 5090 Leverkusen | Process for the production of solid preparations of poorly soluble active pharmaceutical ingredients in extremely fine distribution |
GB1579818A (en) * | 1977-06-07 | 1980-11-26 | Yamanouchi Pharma Co Ltd | Nifedipine-containing solid preparation composition |
JPS55129221A (en) * | 1979-03-29 | 1980-10-06 | Kaken Pharmaceut Co Ltd | Preparation of oral preparation containing hardly soluble medicine |
CA1146866A (en) * | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
-
1980
- 1980-09-09 DE DE19803033919 patent/DE3033919A1/en not_active Ceased
- 1980-12-27 JP JP55185148A patent/JPS5914446B2/en not_active Expired
-
1981
- 1981-08-25 NO NO812879A patent/NO157368B/en unknown
- 1981-08-28 DE DE8181106729T patent/DE3161838D1/en not_active Expired
- 1981-08-28 AT AT81106729T patent/ATE5761T1/en not_active IP Right Cessation
- 1981-08-28 EP EP81106729A patent/EP0047899B2/en not_active Expired - Lifetime
- 1981-08-31 PT PT73603A patent/PT73603B/en unknown
- 1981-08-31 PH PH26121A patent/PH24097A/en unknown
- 1981-09-01 DD DD81232939A patent/DD201974A5/en not_active IP Right Cessation
- 1981-09-07 NZ NZ198285A patent/NZ198285A/en unknown
- 1981-09-07 GR GR65968A patent/GR78237B/el unknown
- 1981-09-07 FI FI812758A patent/FI72648B/en not_active Application Discontinuation
- 1981-09-07 IL IL63749A patent/IL63749A/en not_active IP Right Cessation
- 1981-09-08 PL PL23295181A patent/PL232951A1/xx unknown
- 1981-09-08 ZA ZA816213A patent/ZA816213B/en unknown
- 1981-09-08 CA CA000385365A patent/CA1180277A/en not_active Expired
- 1981-09-08 IE IE2075/81A patent/IE51549B1/en not_active IP Right Cessation
- 1981-09-08 DK DK396381A patent/DK154326C/en not_active IP Right Cessation
- 1981-09-08 AR AR286686A patent/AR226377A1/en active
- 1981-09-08 AU AU75063/81A patent/AU558331B2/en not_active Expired
- 1981-09-09 HU HU812594A patent/HU184879B/en unknown
Also Published As
Publication number | Publication date |
---|---|
DK154326C (en) | 1995-03-13 |
JPS5914446B2 (en) | 1984-04-04 |
AU558331B2 (en) | 1987-01-29 |
JPS5750913A (en) | 1982-03-25 |
EP0047899B2 (en) | 1996-02-28 |
PT73603A (en) | 1981-09-01 |
DK154326B (en) | 1988-11-07 |
ZA816213B (en) | 1982-09-29 |
PH24097A (en) | 1990-03-05 |
PL232951A1 (en) | 1982-10-11 |
FI72648B (en) | 1987-03-31 |
PT73603B (en) | 1982-11-10 |
EP0047899A1 (en) | 1982-03-24 |
ATE5761T1 (en) | 1984-01-15 |
NO812879L (en) | 1982-03-10 |
IL63749A0 (en) | 1981-12-31 |
NO157368B (en) | 1987-11-30 |
DK396381A (en) | 1982-03-10 |
IL63749A (en) | 1984-06-29 |
HU184879B (en) | 1984-10-29 |
EP0047899B1 (en) | 1984-01-04 |
DE3033919A1 (en) | 1982-04-22 |
FI812758L (en) | 1982-03-10 |
NZ198285A (en) | 1984-04-27 |
AU7506381A (en) | 1982-03-18 |
CA1180277A (en) | 1985-01-02 |
DE3161838D1 (en) | 1984-02-09 |
DD201974A5 (en) | 1983-08-24 |
GR78237B (en) | 1984-09-26 |
AR226377A1 (en) | 1982-06-30 |
IE812075L (en) | 1982-03-09 |
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