NZ198285A - Solid pharmaceutical compositions containing a specific form of nifedipine crystals - Google Patents
Solid pharmaceutical compositions containing a specific form of nifedipine crystalsInfo
- Publication number
- NZ198285A NZ198285A NZ198285A NZ19828581A NZ198285A NZ 198285 A NZ198285 A NZ 198285A NZ 198285 A NZ198285 A NZ 198285A NZ 19828581 A NZ19828581 A NZ 19828581A NZ 198285 A NZ198285 A NZ 198285A
- Authority
- NZ
- New Zealand
- Prior art keywords
- nifedipine
- surface area
- specific surface
- solid
- crystals
- 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)
Description
New Zealand Paient Spedficaiion for Paient Number 1 98285
1 982 85
Oj^umvcu-iut*- s si^jw. t • • •
CSaes:
Publication Dnte:
.7 SEP W®' ?
N.Z. No.
NEW ZEALAND Patents Act, 1953 1
COMPLETE SPECIFICATION
"SOLID MEDICAMENT FORMULATIONS CONTAINING NIFEDIPINE, AND PROCESSES FOR_THElR PREPARATION._
We, BAYER AKTIENGESELLSCHAFT, a Company registered under the laws of the Federal Republic of Germany, of Leverkusen, Germany,
do hereby declare the invention, for which we pray that ^ Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement
(Followed by 1A.)
198285
- i/»-
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. British Patent Specification 1,173,862). Because nifedipine is sensitive to light and sparingly soluble, a number of difficulties occur in the galenical 10 .formulation of medicamental 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 15 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 20 which the poor solubility of nifedipine is said to be compensated by using certain solubilising agents and , ,
I* Gt &
surface-active substances are also described in IDT OC ^-Gorman PufrliiRhod Spo oifioation)—2 3 820,882/ The ease of absorption of nifedipine as a result of using polyethylene 25 glycol and certain porous ex-cipient substances is also said improved in European Published Tatent ApplioatiGn
All previous attempts to compensate the poor solubility of nifedipine by certain measures and at the 30 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 35 preparations are undesirably large in size. In order to , facilitate swallowing, such tablets, or capsules are ■frequently converted into particular shapes, • such as,
1 98 2 8
. 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 feiw 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
2
area of 0.5 to 6 m /g, in admixture with a solid diluent. 25 The invention also provides a solid medicament in dosage unit form comprising nifedipine crystals with a o
specific surface area of 0.5 to 6m /g.
The invention also provides a medicament in the form of tablets (including lozenges and granules), 30 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 35 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
T ry ifV TQ' t-f|7
1 982 85
. each containing a daily: dose or a multiple :(up. to; 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. 5 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 15 . 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 20 accelerators, e.g. quaternary ammonium compounds; (g)
surface active agents, e.g. cetyl alcohol, glycerol mono-stearate; (h) adsorptive carriers, e.g. kaolin and benton-ite; (i) lubricants, e.g. talc, calcium and magnesium stearate and solid polyethyl glycols.
The tablets, dragees, c-apsules 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 30 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 35 . form together with one or several of the above-mentioned . diluents. •
bL k 00 '147
1 98285
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 pharmaceutical^ active compounds.
Any diluent in the medicaments of the present invention 15 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 20 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 25 active ingredient. Some, surch 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
2
area of 1 to 4 m /g are particularly advantageous.
The nifedipine crystals which have a specific surface 2
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, 35 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.
1 982 85
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 p
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. 10 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
2
a specific surface area of 0.5 to 6 m /g by grinding or 15 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: 20 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 25 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 crystal-30 line 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 35 considerable advantage is that very small tablets with a high . .content, ;of active, .compound can be. prepared, since solubilising agents, surface-active substances and
"Lo '"A* 20''
982 8 S
• and additional auxiliaries' can 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 5 of coronary illnesses over relatively long periods, and also prophylactically, and furthermore, this formulation presents the possibility of employing the typ.otens.ive action of nifedipine for the treatment of hypertonia. The long-lasting blood level of the active compound which 10 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.
From the knowledge of the state of the art, from 15 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 20 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 25 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 30 can be seen from the following table:
1 98 285
: Tattle Time
(hours) 1. ... 2 3 4. ... .6. ... .8 1.0. . . 25-.5
Plasma concentration, ug/'l after peroral administration of the 105.8 86.1 65.3 63-9 ^3.1 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 5 the invention.
Example 1
200 g of nifedipine crystals with a specific
2
surface area of 4 m /g were mixed with 348 g of micro-crystalline cellulose, 100 g of lactose, 10 g of "Tween" 80, 10 (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. 15 These tablets were then labelled; they had a diameter of 6 mm.
A suspension of 18 g of hydroxypropylmethyl-cellulose, 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 2
surface area of 1 m /g were pres.s.ed to 80 mg tablets with a diameter of 6 mm and filmcoated analogously to Example 1.
Juii' 'ft gO' ''HIT
Claims (7)
1. A solid pharmaceutical composition containing as the active ingredient nifedipine crystals with a specific p 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 m2/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 pharmaceut ical composition according to claim 1, in which nifedipine crystals obtained from their synthesis are converted into a crystal mixture with a specific surface area of 0.5 to p 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|Tor use in combating circulatory illnesses and hypertension. BAYER AKTIENGESELLSCHAFI By HfsTTheir Attorneys,^--HEN.., ..oJhES LIMITED, fLia: A -QO' ,|I|1'7- M7- PATENT OFF ICE 16 DEC 1983
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 (1)
Publication Number | Publication Date |
---|---|
NZ198285A true NZ198285A (en) | 1984-04-27 |
Family
ID=6111496
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ198285A NZ198285A (en) | 1980-09-09 | 1981-09-07 | Solid pharmaceutical compositions containing a specific form of nifedipine crystals |
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 |
---|---|---|---|---|
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 |
NL194389C (en) * | 1984-06-14 | 2002-03-04 | Novartis Ag | Process for preparing a solid dispersion of a pharmaceutically active agent that has low water solubility in a solid matrix of a water-soluble polyalkylene glycol as a carrier. |
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 |
US6726930B1 (en) | 1993-09-09 | 2004-04-27 | Penwest Pharmaceuticals Co. | Sustained release heterodisperse hydrogel systems for insoluble drugs |
US5455046A (en) * | 1993-09-09 | 1995-10-03 | Edward Mendell Co., Inc. | Sustained release heterodisperse hydrogel systems for insoluble drugs |
US5773025A (en) * | 1993-09-09 | 1998-06-30 | Edward Mendell Co., Inc. | Sustained release heterodisperse hydrogel systems--amorphous drugs |
US5543099A (en) * | 1994-09-29 | 1996-08-06 | Hallmark Pharmaceutical, Inc. | Process to manufacture micronized nifedipine granules for sustained release medicaments |
WO1996020707A1 (en) * | 1994-12-29 | 1996-07-11 | Dr. Rentschler Arzneimittel Gmbh & Co. | Pharmaceutical preparations containing nifedipine and process for producing it |
JP3220373B2 (en) | 1995-11-28 | 2001-10-22 | バイエル薬品株式会社 | Long-acting nifedipine preparation |
IL123505A (en) * | 1996-07-08 | 2004-12-15 | Penwest Pharmaceuticals Compan | 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 |
MXPA01005370A (en) | 1999-09-30 | 2004-05-14 | Penwest Pharmaceuticals Co | Sustained release matrix systems for highly soluble drugs. |
EP1741712B1 (en) | 2004-07-30 | 2011-06-15 | Torrent Pharmaceuticals Ltd | amorphous form of nebivolol hydrochloride and its preparation |
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 EP EP81106729A patent/EP0047899B2/en not_active Expired - Lifetime
- 1981-08-28 AT AT81106729T patent/ATE5761T1/en not_active IP Right Cessation
- 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 GR GR65968A patent/GR78237B/el unknown
- 1981-09-07 FI FI812758A patent/FI72648B/en not_active Application Discontinuation
- 1981-09-07 NZ NZ198285A patent/NZ198285A/en unknown
- 1981-09-07 IL IL63749A patent/IL63749A/en not_active IP Right Cessation
- 1981-09-08 CA CA000385365A patent/CA1180277A/en not_active Expired
- 1981-09-08 AR AR286686A patent/AR226377A1/en active
- 1981-09-08 IE IE2075/81A patent/IE51549B1/en not_active IP Right Cessation
- 1981-09-08 ZA ZA816213A patent/ZA816213B/en unknown
- 1981-09-08 DK DK396381A patent/DK154326C/en not_active IP Right Cessation
- 1981-09-08 AU AU75063/81A patent/AU558331B2/en not_active Expired
- 1981-09-08 PL PL23295181A patent/PL232951A1/xx unknown
- 1981-09-09 HU HU812594A patent/HU184879B/en unknown
Also Published As
Publication number | Publication date |
---|---|
HU184879B (en) | 1984-10-29 |
PL232951A1 (en) | 1982-10-11 |
ZA816213B (en) | 1982-09-29 |
EP0047899B1 (en) | 1984-01-04 |
JPS5914446B2 (en) | 1984-04-04 |
EP0047899B2 (en) | 1996-02-28 |
PT73603A (en) | 1981-09-01 |
DK396381A (en) | 1982-03-10 |
NO812879L (en) | 1982-03-10 |
GR78237B (en) | 1984-09-26 |
DK154326B (en) | 1988-11-07 |
FI72648B (en) | 1987-03-31 |
ATE5761T1 (en) | 1984-01-15 |
IL63749A0 (en) | 1981-12-31 |
AU558331B2 (en) | 1987-01-29 |
DE3161838D1 (en) | 1984-02-09 |
PH24097A (en) | 1990-03-05 |
IL63749A (en) | 1984-06-29 |
NO157368B (en) | 1987-11-30 |
AR226377A1 (en) | 1982-06-30 |
CA1180277A (en) | 1985-01-02 |
PT73603B (en) | 1982-11-10 |
EP0047899A1 (en) | 1982-03-24 |
AU7506381A (en) | 1982-03-18 |
DK154326C (en) | 1995-03-13 |
FI812758L (en) | 1982-03-10 |
DD201974A5 (en) | 1983-08-24 |
DE3033919A1 (en) | 1982-04-22 |
IE812075L (en) | 1982-03-09 |
JPS5750913A (en) | 1982-03-25 |
IE51549B1 (en) | 1987-01-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5264446A (en) | Solid medicament formulations containing nifedipine, and processes for their preparation | |
NZ198285A (en) | Solid pharmaceutical compositions containing a specific form of nifedipine crystals | |
US4689233A (en) | Coronary therapeutic agent in the form of soft gelatin capsules | |
CA1140853A (en) | Cerebral therapeutic agent and its use | |
DK170223B1 (en) | Ranitidine-containing effervescent composition and process for its preparation | |
HRP20030527A2 (en) | Pharmaceutical compositions comprising amlodipinemaleate | |
UA46001C2 (en) | CRYSTALLINE HYDROCHLORIDE OF VALACYCLOVIR (OPTIONS), METHOD OF OBTAINING CRYSTAL VALACYCLOVIR AND METHOD OF TREATMENT OF HUMAN HYPHYNUS | |
HU226131B1 (en) | Valaciclovir tablets containing colloidal silicon dioxide and process for producing them | |
AU2001290354A1 (en) | Pharmaceutical compositions comprising amlodipine maleate | |
TW200819144A (en) | Composition with increased photo-stability | |
EP0874631B1 (en) | Use of valaciclovir for the manufacture of a medicament for the treatment of genital herpes by a single daily application | |
LT5815B (en) | Stable pharmaceutical composition of combinations | |
US4888343A (en) | Pharmaceutical compositions for relief of dysmenorrhea and/or premenstrual syndrome and process | |
CA2325014C (en) | 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5h-benzo[5,6]cyclohepta[1,2-b]pyridine oral compositions | |
AU739466B2 (en) | Treatment and prevention of cardiac disorders using selective serotonin re-uptake inhibitors (SSRI) | |
US5399571A (en) | Neuroprotective drug | |
JPH037645B2 (en) | ||
CA2169735A1 (en) | Oral compositions of h2-antagonists | |
CS276556B6 (en) | Pharmaceutical with a controllable bio-disposal of active component | |
HU211747A9 (en) | Drugs containing verapamil and trandolapril | |
KR0141648B1 (en) | Pharmaceutical composition for the treatment of b-type hepatis | |
JPS63150224A (en) | Ameliorant for cerebral function | |
JPH0544925B2 (en) | ||
HUT52384A (en) | Process for producing pharmaceutical compositions comprising dianhydrohexitol acyl derivatives | |
HU213101B (en) | Process for producing pharmaceutical composition of synergetic gastrocitoprotective activity, containing ranitidine and derivative of the salicylic acid |