EP0227814A1 - Therapeutic formulations with bimodal release characteristics - Google Patents
Therapeutic formulations with bimodal release characteristicsInfo
- Publication number
- EP0227814A1 EP0227814A1 EP19860904573 EP86904573A EP0227814A1 EP 0227814 A1 EP0227814 A1 EP 0227814A1 EP 19860904573 EP19860904573 EP 19860904573 EP 86904573 A EP86904573 A EP 86904573A EP 0227814 A1 EP0227814 A1 EP 0227814A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- bimodal
- metolose
- sustained release
- therapeutically active
- weight
- 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.)
- Pending
Links
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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Matériau de base porteur destiné à être combiné avec un médicament thérapeutiquement actif et formé dans une unité de dosage solide de forme prédéterminée permettant de contrôler la libération du médicament lors de son administration. Plus précisément, la présente invention se rapporte à un matériau de base porteur formé d'une ou de plusieurs hydroxypropylméthylcellulose(s) (B-HPMC) bimodales ayant une structure physique et chimique qui rend ledit matériau utilisable dans des formulations thérapeutiques de libération soutenue présentant des caractéristiques de libération bimodales.Carrier base material to be combined with a therapeutically active drug and formed in a solid dosage unit of predetermined shape for controlling the release of the drug during administration. More specifically, the present invention relates to a carrier base material formed by one or more bimodal hydroxypropylmethylcellulose (B-HPMC) having a physical and chemical structure which makes said material usable in sustained release therapeutic formulations having bimodal release characteristics.
Description
THERAPEUTIC FORMULATIONS WITH BIMODAL RELEASE CHARACTERISTICS BRIEF SUMMARY OF THE INVENTION
This invention relates to a oarrier base material to be combined with a therapeutically active medicament and formed into a solid, shaped dosage unit having a bimodal controlled release of medicament upon administration. Specifically, this invention relates to a carrier base material consisting of one or more bimodal hydroxypropylmethylcelluloses (B-HPMC's) having a physical and chemical structure which renders it suitable for use in sustained release therapeutic formulations with bimodal release characteristics.
BACKGROUND OF THE INVENTION
The use of various hydroxypropylmethylcelluloses in carrier base materials to be combined with a therapeutically active medicament and formed into solid, shaped dosage units so as to provide a regular and prolonged release of medication upon administration is well known.
See, for example, U.S. Patent Nos. 4,389,393; 4,369,172; 4,259,314; 4,357,469; 4,226,849; 3,870,790; 3,065,143; and 4,167,558.
The goal of formulators of sustained release pharmaceuticals has long been to provide a substantially constant rate of release, i.e., a zero order release rate or a drug release rate equal to the square root of time rather than a bimodal rate of release. (See FIGURES 1 and 2).
In Forest U.S. Patent 4,369,172, hydroxypropylmethylcellulose (methoxy content of 27 to 30%, hydroxypropyl content of 9 to 12% ) is combined with ethylcellulose or sodium carboxymethylcellulose for prolonged release. Another Forest U.S. Patent 3, 870,790 mentions a slow release buccal tablet of 80 to 100% hydroxypropylmethylcellulose (methoxy content 28 to 30%, hydroxypropyl content 7-12%) and 0 to 20% ethylcellulose. Forest U.S. patent 4,357,469 uses a hydrolyzed and oxidated hydroxypropylmethylcellulose (methoxy content 28 to 30% hydroxypropyl content 7.5 to 12%) with up to 30% ethylcellulose or 30% sodium carboxymethylcellulose. Forest German Patent DT2718-260 describes the use of a treated hydroxypropylmethylcellulose and ethylcellulose to produce a slow release formulation. Forest Patents U.S. 4,226,849 and South Africa 7,805,528 claim similar slow release formulations using hydroxypropylmethylcellulose. In U.S. Patent
3 , 590 , 1 1 7 a h i gh v i s c o s i t y gr a de 1 5 , 000 cps. hydroxypropylmethylcellulose is used for a sustained release
tablet that is at least 1/3 by weight hydrophilic gum. Methocels listed are E4-M, 90 HG 4,000 cps., K4-M, and K15-M. U.S. Patent 4,389,393 claims a carrier base material being one or more hydroxypropylmethylcelluloses (methoxy content 16 to 24%, hydroxypropyl content 4 to 32% and average molecular weight of at least 50,000) up to
30% by weight of a mixture of methylcellulose, sodium carboxymethylcellulose and/ or other cellulose ethers. American Home Products Corp., Patent G.B. 2053-682 describes the preparation of a sugar coated s ustained release tablet us i n g hydroxypropylmethylcellulose (4,000 to 40,000 viscosity grades, 30 to
45% of total weight) In combination with ethylcellulose. Two other American Home Products Corp., U.S. Patents 4,309,405 and U.S. 4,309,406 mention a sustained release tablet using mixtures of hydroxypropylmethylcellulose in the core. Hoffman-LaRoche U.S. Patent 4,167,558 claims aspirin tablets made with mixtures of various cellulose derivatives comprised of 20 to 75% of the total tablet weight. U.S. Patent 4,259,314 describes the preparation of a slow release formulation of 80 to 95% hydroxypropylmethylcellulose (viscosity: 50- 4,000 cps.) and 5 to 20% hydroxypropylcellulose. U.S. Patent 3,065,143 uses a cellulose product with a methoxyl content of 19 to 24% and hydroxypropyl content of 4 to 12% with the HPMC comprising at least 1/3 of the total tablet weight. Sumitomo Chemical K.K. Patents J5-8135-807-A and J5-7062-224 use hydroxypropylmethylcellulose as a coating for tablets. The effect of various METHOCEL Products on Tablet Dissolution, including F4-M, is the subject of a Dow booklet entitled Formulating Sustained Release Pharmaceutical Products with Methocel".
Metolose 65SH-4000 has been reported to be useful as a paint thickener, as a suspending agent in spray paints, as a thickener in paint removers, as a latex stabilizer and thickener for asphalt emulsion, as a base of jelly for an external application or ointments, as a binder for cigar leaf. Metolose 65SH-1500, as a gypsum plaster additives. Metolose 65SH-400 as Joint cement additive, as suspension stabilizer in vinyl chloride vinylidene polymer, as latex stabilizer, as spray paint additive, as shampoo additive to improve viscosity.
Metolose 65SH-50, as suspension stabilizer in vinylchlorlde vinylidene polymer. Metolose 90SH-100 as suspension stabilizer in vinylchlorlde
vinylidene polymer, as molding binder for pencil or crayons. Metolose 90SH-15000 as cement mortar additive, as tile cement additive, as gypsum plaster additive, as plaster additive, as molding product of gypsum cement. Metolose 60SH-4000 as paint remover additive, as shampoo additive, as binder for the extrusion molding of ceramic condenser and ferrite alumina porcelains. Methocel F4-M as additive to general adhesives, dust stickers, spray stickers, caulking compounds, tile and grout adhesives, toothpastes, pie fillings, cements, creams, ointments, ophthalmic preparations, and suspensions. DETAILED DESCRIPTION
The present invention is directed toward a carrier base material for therapeutically active medicaments in a solid dosage formulation that produces a bimodal controlled release profile characterized by a rapid initial release of aedicament followed by a substantially constant rate of release for a period of time, after which the release rate is greater than the constant rate previously observed.
The advantages of the present invention, a carrier base material and bimodal controlled release formulation prepared therefrom, over conventional sustained release formulations are substantial. Conventional sustained release formulations may exhibit a zero order release profile, where the rate of release of therapeutic agent is essentially constant, or a profile in which the release rate decreases with time. As a conventional controlled release tablet moves through the gastrointestinal tract, drug absorption decreases. An objective of the bimodal controlled release formulation of this invention is to provide for a more uniform delivery of therapeutic agent since it is now possible to increase the rate of drug release at a point when the body's ability to absorb a medicament decreases, thus providing more uniform delivery of the therapeutic agent. Another object of the present invention is to provide a bimodal formulation giving therapeutic blood levels similar to those produced by administration of two smaller doses over an extended period of time.
The bimodal release profile of the active ingredient from the carrier of the present invention can be controlled according to the particlar therapeutic agent and its intended therapeutic effect since the initial rate of release, initial time of rate change, and the final release rate for a specific drug, are all a property of the particular
B-HPMC(s) utilized. These parameters can be selectively modified by the addition of various excipients that include, but are not limited to, non-bimodal hydroxypropylmethylcellulose (HPMC's), hydroxypropylcelluloses, lactose, starch, binders, fillers, disintegrating agents and other pharmaceutical compounding agents.
The active ingredient can be any type of therapeutic agent which lends itself to controlled release administration. Examples of such agents include antihistamines, laxatives, vitamins, decongestants, gastrointestinal sedatives, anti-inflammatory substances, antacids, anti-infectives, coronary vasodilators, cerebral vasodilators, peripheral vasodilators, psyehotropics, antimanics, stimulants, antidiarrheal preparations, antianginal drugs, vasoconstrictors, anticoagulants, antithrombotic drugs, analgesics, anti-pyretics, hypnotics, sediatives, anti-emetics, anti-nauseants, anticonvulsants, neuromuscular drugs, hyper- and hypoglycemic agents, thyroid and antithyroid preparations, diuretics, anti-spasmodics, uterine relaxants, mineral and nutritional additives, antiobesity drugs, anabolic drugs, erythropoietic drugs, anti-asthmatics, expectorants, cough suppressents, mucolytics, antiuricemic drugs, etc. The preparation of sustained release tablets with bimodal release characteristics consists of thorough mixing of a therapeutic agent with one or more of the hydroxypropylmethylcellulose ethers of the present invention, and any other ingredients wMch are. conventional in tablet making - such as magnesium stearate, stearic acid, Cab-O-sil (colloidal 3ilicon dioxide) etc. Release rate modifiers, as mentioned previously, are also added at this time, if they are desined. All ingredients are mixed thoroughly. The mixture, in an amount sufficient to make a uniform batch of matrix tablets, is subjected to tableting on conventional tableting machines. Those hydroxypropylmethylcellulose ethers effective for the present purpose are the bimodal hydroxypropylmethylcellulose ethers (B-HPMC's), with a methoxy content of 19 to 30%, a hydro xypropyoxy content of from 4 to 12%, a viscosity of from 40 to 19,000 cps, an average molecular weight of from 20,000 to 140,000, and demonstrates a bimodal release profile in accordance with the assay described in Procedure I. Accordingly, any hydroxypropylmethylcellulose ether having the foregoing specifications, and exhibiting a bimodal release profile in
accordance with Procedure I represents a B-HPMC.
Examples of commercially available hydroxypropylmethylcellulose ethers which can be used as B-HPMC's include, but are not limited to, Metolose 65SH-50, 400, 1500 and 4000, Metolose 60SH-4000 and Metolose 90SH-100 and 15,000, all available from Shin-Etsu Ltd., Japan, as well as Methocel F4-M available from the Dow Chemical Company. Various grades of Methocel A, E and K tested do not demonstrate a bimodal release profile nor has Metolose SM-1500, a brand of methylcellulose. See, for example, the cumulative and differential plots of a 200 mg flurbiprofen/Methocel 30% K15-M of FIGURES 3 and 4.
To prepare a solid dosage formulation with bimodal release characteristics, at least one B-HPMC must be utilized. The content of the B-HPMC (s) may comprise about 5 to about 99% by weight of the total formulation, depending upon the active ingredient and length of drug release desired. The bimodal hydroxypropylmethylcelluloses (B-HPMC's) of the present invention can be optionally mixed with about 0 to 50% by weight of the total formulation of a non-bimodal hydroxypropylmethylcellulose, or methylcellulose, sodium carboxymethylcellulose or other cellulsoe ether. For example, two or more B-HPMC's, one or more non-bimodal HPMC, or other cellulose ethers in combination with one or more B-HPMC can be mixed to provide bimodal formulations of various specific release characteristics. See e g. Example 11 and 12. Procedure 1 Determination of Bimodal Hydroxypropylmethyl-cellulose (B-HPMC's) Utilizing Standard In Vitro Assay Procedures
The ability of hydroxypropylmethylcelluloses to produce a bimodal release profile can be readily evaluated in accordance with the following procedure.
One Hundred 300 mg Aspirin tablets are prepared from the following types and amounts of ingredients:
Aspirin 30 gm
HPMC (test material) 20.7 gm
Stearic Acid 0.881 gm
Cab-O-Sil 0.176 gm The HPMC, aspirin, stearic acid and Cab-O-Sil are mixed thoroughly with a mechanical mixer for about 5 minutes. The mixture 13 tableted (Carver press, 4.8x10am. eliptlcal die) with a compression force of
3,500 lbs for 30 seconds.
Release rates are determined using an automated spin filter dissolution apparatus, J. Pharm. Sci. 63. 110, (1974), or other dissolution test device using the following conditions: Media: 1,000 ml of 0.05 M phosphate buffer, pH 7.2
Temperature: 37 degrees C Stirring Speed: 300 rpm Spectrophotometer: Perkin-Elmer Lambda 5 Wavelength: 296 nm Sampling Interval: 60 minutes
Release rates are plotted (cumulative and/ or differential plots) and evaluated for the presence of a bimodal profile characterized by a rapid initial release of drug followed by am essentially constant rate of release .for a period of time, after which the release rate is greater than the constant rate previously observed. An HPMC that produces a bimodal release rate is a B-HPMC.
For example, 300 mg aspirin tablets prepared as described above and using Metolose 65SH-4000 as the HPMC had the following percentage drug dissolved as a function of time. Time
(Hours) % Dissolved Rate
1 11.0 11.0
2 17.0 6.0
3 22.0 5.0 4 27.0 5.0
5 33.0 6.0
6 39.0 6.0
7 46.0 7.0
8 54.0 8.0 9 63.0 9.0
10 72.0 9.0
11 80.0 8.0
12 86.0 6.0
13 91.0 5.0 14 96.0 4.0
15 100.0 4.0
16 100.0 0.0
17 100.0 0.0
18 100.0 0.0 Cumulative and differential plots of the test data can be prepared and evaluated to more clearly illustrate the bimodal release profiles. (See FIGURES 5 and 6). Metolose 65SH-4000 is a B-HPMC.
The following methods describe the manner and process of using this invention and are to be construed as exemploary embodiments of the invention concept and not as limitations thereof.
Examples 1-3: Bimodal Controlled Release 200 mg flurbiprofen tablets containing 40% bimodal hydroxypropylmethylcellulose were prepared from the following ingredients: Example 1 :
Ingredients mg/Tablet Wt.%/Tablet
Flurbiprofen 200 58.0
Metolose 65SH- -50 138 40.0
Stearic Acid 5.87 1.70
Cab-O-Sil 1.17 0.34
Example 2:
Flurbiprofen 200 58.0
Metolose 65SH- -1500 138 40.0
Stearic Acid 5.87 1.70
Cab-O-Sil 1.17 0.34
Example 3:
Flurbiprofen 200 58.0
Metolose 65SH- -4000 138 40.0
Stearic Acid 5.87 1.70
Cab-O-Sil 1.17 0.34
All ingredients are mixed for 5 min. The mixtures are then subjected to a compression force of 2,500 psi/30sec. The theoretical weight of the tablets is 345 mg. Release rates are determined, for all examples, using an automated spin-filter dissolution apparatus under the following dissolution conditions:
Media: 1,000 ml of 0.05 M phosphate buffer pH 7.20 Temperature: 37°C Stirring Speed: 300 rpm
Sampling interval: 30 min. Table 1 shows the percent drug dissolved per hour, and the rate of
dissolution for Examples 1-3.
Examples 4-9: Examples 4-9 show the effect of varying the amount of a bimodal hydroxypropylmethylcellulose used on 200 mg flurbiprofen formulations.
Example 4:
Ingredients mg/Tablet Wt.%/Tablet
Flurbiprofen 200 83.0
Metolose 90SH-100 36.2 15.0
Stearic Acid 4.10 1.70
Cab-O-Sil 0.819 0.34
Example 5:
Flurbiprofen 200 78.0
Metolose 90SH-100 51.6 20.0
Stearic Acid 4.39 1.70
Cab-O-Sil 0.877 0.34
Example 6 :
Flurbiprofen 200 68.0
Metolose 90SH- -100 88.2 30.0
Stearic Acid 5.00 1.70
Cab-O-Sil 1.00 0.34
Example 7 :
Flurbiprofen 200 58.0
Metolose 90SH- -100 138 40.0 Stearic Acid 5.87 1.70
Cab-O-Sil 1.17 0.34
Example 8:
Flurbiprofen 200 48.0
Metolose 90SH- -mo 209 50.0
Stearic Acid 7.09 1.70
Cab-O-Sil 1.42 0.34
Example 9 :
Flurbiprofen 200 38.0
Metolose 90SH- -100 316 60.0
Stearic Acid 8.96 1.70
Cab-O-Sil 1.79 0.34
Tablets are prepared and tested as stated in Examples 1-3. Tablet weight ranges from 241 mg to 527 mg. Table 2 shows the percent drug
dlssolved per hour, and rate of dissolution for Examples 4-9.
Examples 10-12: Examples 10-12 show the effect of a modifying excipient, Metolose SM-1500 (methylcellulose, USP; 1500 cps), on 30 mg adinazolam mesylate formulations containing the bimodal hydroxypropylmethylcellulose, Metolose 65SH-4000. Example 10:
Ingredients Mg/Tablet Wt.%/Tablet
Adinazolam mesylate 30.0 7.96
Metolose 65SH-4000 339 90.0
Stearic Acid 6.41 1.70
Cab-O-Sil (Colloidal 1.28 0^34
Silicon Dixoide)
Example 11 :
Adinazolam mesylate 30.0 7.96
Metolose 65SH-4000 207 55.0
Metolose SM-1500 132 35.0
Stearic Acid 6.41 1.70
Cab-O-Sil (Colloidal 1.28 0.34
Silicon Dioxide)
Example 12:
Adinazolam mesylate 30.0 7.96
Metolose 65SH-4000 170.0 45.0
Metolose SM-1500 170.0 45.0
Stearic Acid 6.41 1.70
Cab-O-Sil 1.28 0.34
All ingredients are mixed for 5 min. The mixture is then subjected to a compression force of 3,500 psi/30 sec. The theoretical weight of the tablets is 377 mg. Release rates are determined as stated in Examples 1-3. Percent drug dissolved per hour and rate of dissolution are given in Table 3. Example 13:
Ingredients Mg/Tablet Wt.%/Tablet
Flurbiprofen 200 64.3
Metolose 90SH-100 77.0 24.7
Metolose 90SH-4000 31.0 9.96
Stearic Acid 2.00 0.643
Cab-O-Sil (Colloidal 1.00 0.321
Silicon Dixoide)
38-42% FDSC Yellow No. 6 0.28 0.0900
Example 14:
Flurbiprofen 200 64.3
Metolose 90SH-100 61.5 19.8
Metolose 90SH-4000 46.5 14.9
Stearic Acid 2.00 0.643
Cab-O-Sil 1.00 0.321
38-42% FD&C Yellow No. 6 0.28 0.0900
Example 15:
Flurbiprofen 200 64.3
Metolose 90SH-100 92.5 29.7
Metolose 90SH-4000 15.5 4.98
Stearic Acid 2.00 0.643
Cab-O-Sil 1.00 0.321
38-42% FD&C Yellow No. 6 0.28 0.0900
Method of Preparation:
Tablets are prepared in Examples 13, 14 and 15 by mixing flurbiprofen, metoloses, and color in a P-K blender for 5 min. The mixed are then dry granulated by slugging. The stearic acid and Cab-O- Sil are added to the dry sized granules and blended for another 5 min. Mixos are then compressed on a Beta Press. The theoretical tablet weight is 311.28 mg. Table 4 shows the percent drug dissolved versus time and the rate for the tablets.
Claims
1. A carrier base material combined with a therapeutically active medicament and shaped and compressed to a solid sustained release pharmaceutical dosage form having a bimodal release profile upon administration, carrier base material being one or more hydroxypropylmethylcelluloses and up to 50? by weight of the mixture of methylcellulose, sodium carbodymethylcellulose and/ or other cellulose ether, and wherein at least one of the hydroxypropylmethylcelluloses, is a bimodal hydroxypropylmethylcellulose (B-HPMC) having a methoxy content of 19-30% by weight, a hydroxypropyl content of 4-12% by weight and an average molecular weight of 20,000-140,000.
2. A bimodal sustained release pharmaceutical formulation according to Claim 1 in which the carrier base material consists of one or more bimodal hydroxypropylmethylcelluloses selected from the group consisting of:
Metolose 60SH-4000,
Metolose 65SH-50,
Metolose 65SH-400, Metolose 65SH-1500,
Metolose 65SH-4000,
Metolose 90SH-100,
Mecolose 90SH-15000, or
Methocel F4-M.
3. A bimodal sustained release pharmaceutical formulation according to Claim 1 in which the therapeutically active medicament is selected from the group consisting of: antihistamines , laxatives, vitamins, deconges tants, gastrointestinal sedatives, anti-inflammatory substances, antacids, anti-infectives, coronary vasodilators, cerebral vasodilators, peripheral vasodilators, psychotropics, antimanics, stimulants, antidiarrheal preparations, antianglnal drugs, vasoconstrictors, anticoagulants, antithrombotic drugs, analgesics, anti-pyretics, hypnotics, sedtatives, anti-emetics, anti-nauseants, anticonvulsants, neuromuscular drugs, hyper- and hypoglycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, mineral and nutritional additives, antiobesity drugs, anabolic drugs, erythropoietic drugs, anti-asthmatics, expectorants, cough suppressents, mucolytics and antiuricemic drugs.
4. A bimodal sustained release pharmaceutical formulation according to Claim 1 in which the therapeutically active medicament is flurbiprofen.
5. A bimodal sustained release pharmaceutical formulation according to Claim 1 in which the therapeutically active medicament is adinazolam or a pharmaceutically acceptable salt thereof.
6. A bimodal sustained release pharmaceutical formulation according to Claim 1 in which the therapeutically active medicament is adinazolam mesylate.
7. A bimodal sustained release pharmaceutical formulation according to Claim 1 in which the therapeutically active medicament is an antiinflammatory drug selected from the group consisting of ibuprofen, flurbiprofen, diclofenac, indomethacin, naproxen or naproxen sodium.
8. A method for the preparation of a bimodal sustained release pharmaceutical formulation containing a therapeutically active medicament and having a bimodal release profile upon administration, consisting of compressing and shaping a mixture of a therapeutically active medicament and a carrier base material consisting of one or more hydroxypropyl-methylcelluloses and up to 50% by weight of the mixture of methylcellulose, sodium carbodymethylcellulose and/or other cellulose ether , and wherein at least one of the hydroxypropylmethylcelluloses, is a bimodal hydroxypropylmethylcellulose (B-HPMC) having a methoxy content of 19-30% by weight, a hydroxypropyl content of 4-12% by weight and an average molecular weight of 20,000-140,000.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75112585A | 1985-07-02 | 1985-07-02 | |
| US751125 | 1985-07-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0227814A1 true EP0227814A1 (en) | 1987-07-08 |
Family
ID=25020588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19860904573 Pending EP0227814A1 (en) | 1985-07-02 | 1986-06-18 | Therapeutic formulations with bimodal release characteristics |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP0227814A1 (en) |
| WO (1) | WO1987000044A1 (en) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4786503A (en) * | 1987-04-06 | 1988-11-22 | Alza Corporation | Dosage form comprising parallel lamine |
| US4994276A (en) * | 1988-09-19 | 1991-02-19 | Edward Mendell Co., Inc. | Directly compressible sustained release excipient |
| US5472710A (en) * | 1988-04-16 | 1995-12-05 | Schwarz Pharma Ag | Pharmaceutical preparation to be administered orally with controlled release of active substance and method for its manufacture |
| GR1000252B (en) * | 1988-09-02 | 1992-05-12 | Alza Corp | Dose type constituted of quick release of an effective agent |
| US5135757A (en) * | 1988-09-19 | 1992-08-04 | Edward Mendell Co., Inc. | Compressible sustained release solid dosage forms |
| US5128143A (en) * | 1988-09-19 | 1992-07-07 | Edward Mendell Co., Inc. | Sustained release excipient and tablet formulation |
| US5169639A (en) * | 1988-09-19 | 1992-12-08 | Edward Mendell Co., Inc. | Controlled release verapamil tablets |
| US5009895A (en) * | 1990-02-02 | 1991-04-23 | Merck & Co., Inc. | Sustained release with high and low viscosity HPMC |
| US5232704A (en) * | 1990-12-19 | 1993-08-03 | G. D. Searle & Co. | Sustained release, bilayer buoyant dosage form |
| US5472711A (en) * | 1992-07-30 | 1995-12-05 | Edward Mendell Co., Inc. | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
| SI9500173B (en) * | 1995-05-19 | 2002-02-28 | Lek, | Three-phase pharmaceutical form with constant and controlled release of amorphous active ingredient for single daily application |
| US5948437A (en) * | 1996-05-23 | 1999-09-07 | Zeneca Limited | Pharmaceutical compositions using thiazepine |
| US6210710B1 (en) | 1997-04-28 | 2001-04-03 | Hercules Incorporated | Sustained release polymer blend for pharmaceutical applications |
| FR2766707A1 (en) * | 1997-07-30 | 1999-02-05 | Galenix Dev | Medicaments containing cellulose based disintegration agents |
| FR2766708B1 (en) | 1997-07-30 | 2000-05-05 | Galenix Dev | COMPOSITION CONTAINING HYDROXYPROPYLCELLULOSE, HYDROXYPROPYLMETHYLCELLULOSE AND / OR ETHYLCELLULLOSE AS DISINTEGRANTS, AND PROCESS FOR OBTAINING SAME |
| US20010055613A1 (en) | 1998-10-21 | 2001-12-27 | Beth A. Burnside | Oral pulsed dose drug delivery system |
| US6242003B1 (en) | 2000-04-13 | 2001-06-05 | Novartis Ag | Organic compounds |
| US6955821B2 (en) | 2000-04-28 | 2005-10-18 | Adams Laboratories, Inc. | Sustained release formulations of guaifenesin and additional drug ingredients |
| US6372252B1 (en) | 2000-04-28 | 2002-04-16 | Adams Laboratories, Inc. | Guaifenesin sustained release formulation and tablets |
| US20060127474A1 (en) | 2001-04-11 | 2006-06-15 | Oskar Kalb | Pharmaceutical compositions comprising fluvastatin |
| US6913768B2 (en) | 2002-09-24 | 2005-07-05 | Shire Laboratories, Inc. | Sustained release delivery of amphetamine salts |
| CN101400343B (en) | 2006-03-16 | 2012-01-11 | 特瑞斯制药股份有限公司 | Modified release formulations containing drug-ion exchange resin complexes |
| EP2884961B1 (en) | 2012-08-15 | 2019-03-06 | Tris Pharma Inc. | Methylphenidate extended release chewable tablet |
| US11590228B1 (en) | 2015-09-08 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine compositions |
| US11278506B2 (en) | 2015-10-09 | 2022-03-22 | Rb Health (Us) Llc | Pharmaceutical formulation |
| US11590081B1 (en) | 2017-09-24 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine tablets |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4167558A (en) * | 1976-02-13 | 1979-09-11 | Hoffmann-La Roche Inc. | Novel sustained release tablet formulations |
| US4369172A (en) * | 1981-12-18 | 1983-01-18 | Forest Laboratories Inc. | Prolonged release therapeutic compositions based on hydroxypropylmethylcellulose |
| US4389393A (en) * | 1982-03-26 | 1983-06-21 | Forest Laboratories, Inc. | Sustained release therapeutic compositions based on high molecular weight hydroxypropylmethylcellulose |
-
1986
- 1986-06-18 EP EP19860904573 patent/EP0227814A1/en active Pending
- 1986-06-18 WO PCT/US1986/001360 patent/WO1987000044A1/en unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO8700044A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1987000044A1 (en) | 1987-01-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0227814A1 (en) | Therapeutic formulations with bimodal release characteristics | |
| US4695591A (en) | Controlled release dosage forms comprising hydroxypropylmethylcellulose | |
| US4834985A (en) | Controlled release pharmaceutical composition | |
| EP0234670B1 (en) | Sustained-release pharmaceutical formulation containing xanthan gum | |
| US5451409A (en) | Sustained release matrix system using hydroxyethyl cellulose and hydroxypropyl cellulose polymer blends | |
| EP0248548B1 (en) | Controlled release pharmaceutical composition | |
| US4389393A (en) | Sustained release therapeutic compositions based on high molecular weight hydroxypropylmethylcellulose | |
| AU595801B2 (en) | Oral pharmaceutical composition | |
| AU600950B2 (en) | Controlled release dihydrocodeine composition | |
| US6210710B1 (en) | Sustained release polymer blend for pharmaceutical applications | |
| NL193164C (en) | Pharmaceutical tablet for controlled, sustained release of an active compound. | |
| SE453796B (en) | FIXED, THERAPEUTIC COMPOSITION OUR BEARING MATERIAL IS MADE OF HYDROXYPROPYLMETHYL CELLULOSA AND EVEN SODIUM CARBOXYMETHYL CELLULOSA | |
| CN102348458A (en) | Tablet and granulated powder containing 6-fluoro-3-hydroxy-2-pyrazinecarboxamide | |
| JPH10182436A (en) | Solid medicinal preparation | |
| KR100202154B1 (en) | Film coated tablet of paracetamol and domperidone | |
| JP3884056B1 (en) | Method for producing intraoral rapidly disintegrating tablet | |
| JPS63290818A (en) | Slow release tablet based on high molecular hydroxypropylmethyl cellulose and manufacture | |
| JP2002308760A (en) | Composition for compression molding and use thereof | |
| EP0266707B1 (en) | Sustained release labetalol tablet | |
| EP0319074B1 (en) | Pharmaceutical composition and process for its preparation | |
| JP2005053792A (en) | Compression-molded preparation and method for producing the same | |
| JPH10509981A (en) | Sustained drug delivery using powdered hydrocolloid rubber obtainable from higher plants | |
| JPH02121919A (en) | Tablet having flexibility | |
| AU744483B2 (en) | Compressed compositions comprising clarified xanthan gum | |
| JP4828707B2 (en) | Solid compression formulation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: SHAH, ASHOK, C. |