GB1583801A - Oral carrier base its preparation and dosage units made therefrom - Google Patents
Oral carrier base its preparation and dosage units made therefrom Download PDFInfo
- Publication number
- GB1583801A GB1583801A GB8515/77A GB851577A GB1583801A GB 1583801 A GB1583801 A GB 1583801A GB 8515/77 A GB8515/77 A GB 8515/77A GB 851577 A GB851577 A GB 851577A GB 1583801 A GB1583801 A GB 1583801A
- Authority
- GB
- United Kingdom
- Prior art keywords
- weight
- hydroxypropylmethylcellulose
- moisture content
- active medicament
- carrier
- 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.)
- Expired
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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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Description
(54) ORAL CARRIER BASE, ITS PREPARATION AND
DOSAGE UNITS MADE THEREFROM
(71) We, FOREST LABORATORIES.
INC., a corporation organised under the laws of the State of Delaware, of 919 Third
Avenue, New York, United States of
America, do hereby declare the invention, for which we pray that a 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:
This invention relates to an improved oral carrier base, its preparation and dosage units made therefrom.
Hydroxypropylmethylcellulose is known and commercially available as Methocel (trade mark; Dow Chemical Co.) and a premium (pharmaceutical) grade is known as Methocel 60 H.G.-50 viscosity.
Ethylcellulose is also well known and readily available. Methocel has been used as a starting material in making buccal or sublingual products for transmucosally acting medicaments as described in my
British Patents Nos. 1,171,691 and 1,279,214 and U.S. Patent No. 3,870,790.
Compressed buccal lozenges or tablets comprising cellulose derivatives as carriers together with medicinal agents as the active component have been proposed where steady prolonged medication is required and a regular rate of release is needed with good absorption of medicament from an orally ingestible preparation subject to the action of gastric and intestinal fluids. The present invention is directed to improvements in such lozenges or tablets.
According to the present invention, I have now found that further and important advantages and improvements over my prior products containing Methocel as described, for example, in U.S. Patent No.
3,870,790 and British Patents Nos.
1,171,691 and 1,279,214 can be obtained by special treatment thereof under controlled conditions of moisture, temperature and time prior to incorporation of the active medicament therein and thus the inherently desirable properties of Methocel can be taken advantage of in a significantly improved, sustained continuous release, compressed stable tablet capable of providing steady therapeutic blood levels.
The present invention therefore subjects hydroxypropylmethylcellulose to special processing and stabilizing conditions, thereby producing a modified carrier rnaterial base having greater stability, reduced water solubility, greater chemical inertness with freedom from toxicity due to the carrier material itself, less likelihood of impaction and a lowered potential of replacement or chemical changes of anhydroglucose units. The treated carrier material is characterized by a carbonyl content of methylcellulose of 0.92-1.43 grams/100 grams, a methoxyl content of 0.5172 mg (U.S.P. XIX, page 318) and a moisture range preferably of 4.55.5% for best results but within the range of 210% for applicability to various uses independent of the pH of the physiological environment, the carrier material being itself essentially of neutral pH (to litmus paper).
The hydroxypropylmethylcellulose used as the starting material for the present invention is known and commercially available as Methocel 60 H.G.---50 viscosity (Dow Chemical Co.), which is a premium grade found best for pharmaceutical products, and this hydroxypropylmethylcellulose can be optionally admixed with a small proportion of ethylcellulose up to substantially 20% of the weight of the mixture, in which case the hydroxypropylmethylcellulose amounts to 10(#80%. The hydroxpropylmethylcellulose alone or a mixture of these two materials in powder form is processed. The processing is carried out in suitable equipment hereinafter described under the conditions set forth. After the materials have been processed as described, an active ingredient in suitable amount to provide an effective unit dose per tablet is incorporated therein. The active ingredient can be of any type of medication which acts systemically and can be administered orally to transmit the active medicament into the gastro intestinal tract and into the blood stream in therapeutically effective levels without early excessive peak concentrations, without being inactivated by physiological fluids and without passing unchanged through the body of the patient or subject by being excreted unabsorbed.
Representative active medicaments include anti-inflammatory substances, coronary dilator preparations, cerebral dilators, vasodilators, antibaceterials, psychotropics, antimanics, stimulants, and so on. However, it is to be under-stood that the invention is especially applicable to compressed tablets which are intended to be swallowed in unit dosage form, and which upon ingestion according to a prescribed regimen give slow and regular release of active medicament without an initial dumping of a fixed percentage in the intestinal tract while being protected against normally inactivating gastric fluids.
The processed hydroxypropylmethlcellulose alone or with up to 20% of ethylcellulose, by weight, forms what is herein called a long-acting, slow dissolving oral carrier independent of pH and of such nature that it has a protective, demulcent and buffering effect in the body, and causes the active medicament to exert its optimum therapeutic action immediately and incrementally for up to several hours so that full therapeutical advantage can be taken of the entire or substantially the entire amount of active medicament administered. This unexpectedly high degree of efficiency is a particular advantage of the invention, and minimizes the side effects of the medication.
The procedure is carried out by a method which comprises humidifying hydroxypropylmethylcellulose or a mixture of hydroxypropylmethylcellulose with up to 20% by weight ethylcellulose to a moisture content of substantially 85% by weight while in powder form, and de-humidifying the resulting material at elevated temperature until its moisture content is stabilised in the range of 210% by weight, and tableting the thus treated material after admixture with the systemically active ingredient.
In a preferred embodiment the procedure is carried out in accordance with my above-noted Patents by introducing the hydroxypropylmethylcellulose or a mixture of the hydroxypropylmethylcellulose with ethylcellulose into a heating chamber provided with an exhaust which is at that time in a closed or shut position, and which chamber is provided with a heating unit and a forced air blower, which is inoperative at this stage of the procedure in that the heat and forced air are only applied at a subsequent stage. The carrier material to be processed is placed in thin layers (not more than 1/411 thick) on trays of the chamber which are lined with heat-resistant parchment paper, and the trays are placed on racks in the oven chamber using only alternate shelves, thereby providing adequate spacing between the layers of carrier material being treated. There is then placed within the oven chamber a humidifier equipped with a humidistate which is preset to maintain humidity in the oven chamber at substantially 85%, the humidifier being filled with sufficient distilled or deionized water to last for 24 to 36 hours.
The humidifier is now activated, the heating chamber is closed and the process is allowed to proceed under the high humidity conditions for a period of time sufficient to ensure reaching a humidity of the carrier material of at least 85%, and maintaining the latter for up to 24 hours or even longer if desired, although there is no special advantage in exceeding 24 hours and unduly extended times are apt to be uneconomical.
Stibsequent to the 24 hour minimum period just referred to, the humidifier is removed from the heating chamber, the exhaust aperture is opened by manipulation of the usual valve or closure thereof and the forced air blower is activated, thereby applying heat at a controlled temperature in the range of from 1 1(#1200F (43 49 C), and at the end of 12 hours, the moisture content of the treated material is checked by removing and testing a sample. The moisture content must not be less than the range of 22.1/2% in terms of added weight of the carrier material undergoing processing. This added moisture content is equivalent to substantially 1 1 5% as determined by a standard moisture determination apparatus. The 12 hour period just referred to is, however approximate in that the duration of the period may vary somewhat above or below 12 hours, but it has been found in practice that the period should best be approximately 12 hours. The attainment of the specified additional moisture percentage is important and considered critical to the success of the invention.
When the required added moisture content is achieved, in the case of the processing of hydroxypropylmethylcellulose alone, the treated material is removed from the oven and passed through a No. 2 stainless steel screen employing a
Fitzpatrick Comminuter having its knives directed forwardly and operating at medium speed. In the case of the treatment of 10080% hydroxypropylmethylcellulose and 020% ethylcellulose, the comminution step may be omitted and the heat applied until the moisture content is reduced to not less than 2.0% as determined by the usual moisture determination apparatus. Since the material is free-flowing and powdery, no further operation is required thereon.
In one embodiment, tablets containing an orally administrable, systemically absorbable active component such as one of the heretofore mentioned medicaments are made up. The treated oral carrier material is thoroughly intermixed with the medicament which is also in powdered or granular form and with any other necessary ingredients which are conventional in tablet-making such as magnesium stearate, lactose, starch and, in general, binders, fillers, disintegrating agents, and the like.
The complete mixture, in an amount sufficient to make a uniform batch of tablets, such as 50,000, of which each contains an effective amount of active medicament, is then subjected to tableting in conventional tableting machines but at, for example, compression pressures of 7 to 13 kg/in.2. Because of the use of the specially processed carrier material in the production of the tablets, a product is obtained which has a desired set of properties such as predetermined prolonged action and a regular delayed release pattern so that the medicinal agent or active ingredient is available over a period of 1-12 hours depending on the precise tablet size and hardness and the particular carrier mixture. In this way, it is possible to produce sustained or slow, continuous release tablets in relatively simple and economical manner on a commercial scale as contrasted with the more elaborate and more complex materials and procedures heretofore employed or proposed.
The humidifier employed is an Arvin
Model 50 H 42 (Sears Roebuck) - 10 gallon capacity humidifier having low and high air speeds and the humidistat is provided with nine settings for moisture control. In the present invention, the humidistat is set to position 7 which maintains 85 90% humidity in the oven chamber per 250 cubic feet of airflow and a temperature of approximately 75"F (24"C).
It is understood that the invention is not limited to the use of this particular humidifier or equipment and that other equipment may be substituted therefor.
The invention is further illustrated by the following non-limitative examples:
EXAMPLE No. 1
Vasodilator (per 50,000 dosage units) a. Nitroglycerin 325 g.
b. Beta Lactose 2,975 g.
c. Syloid No. 244 (trade mark) 50 g.
d. Cherry flavour 100 g.
e. Synchron Oral-Carrier 23,750 g.
EXAMPLE No. 2
Anti-inflammatory
(per 50,000 dosage units) a. Prednisolone 250 g.
b. Synchron Oral-Carrier 9,465 g.
c. Syloid No. 244 (trade mark) 50 g.
d. Cherry flabour 100 g.
EXAMPLE No. 3
Anti-Manic depressive
(per 50,000 dosage units) a. Lithium Carbonate 15,000 g.
b. Synchron Oral-Carrier 19,880 g.
c. Syloid No. 244 (trade mark) 10 g.
d. Cherry flavour 15 g.
EXAMPLE No. 4
Antacid
(per 50,000 dosage units) a. Aluminium Hydroxide Gel 12,500 g.
b. Magnesium Glycinate. 12,500 g.
c. Gastric Mucin 5,000 g.
d. Carbowax 6000 W (trade mark) 34.5 g.
e. Synchron Oral Carrier 12,000 g.
f. Syloid No. 244 (trade mark) 250 g.
g. Cherry flavour 500 g.
EXAMPLE No. 5
Antibiotic
(per 50,000 dosage units) a: Ampicillin 12,500 g.
b. Synchron Oral-Carrier 2,500 g.
c. Syloid No. 244 (trade mark) 30 g.
d. Cherry flavour 25 g.
The release pattern of active medicament from the new long-lasting oral carrier can be controlled according to the particular medication and its intended therapeutic effect. The release pattern varies from about 1 hour to 8 hours or as long as 12 hours and this is at least in part governed by the tablet size and degree of compression (hardness) since larger tablets last longer and higher compressions give a slower rate of release. For orally administered tablets, the rate of release is usually 4--8 hours and this has been confirmed by X-rays with barium sulphate to show the motility and disintegration in the intestinal tract. For vaginal and rectal suppositories the release pattern ranges from 12-36 hours although it can of course be less where indicated. By predetermining the size of the tablet or suppository and the amount of compression or moulding force employed in shaping it from the powder form, and by keeping the end product moisture content to not less than 2.0%, highly desirable release patterns of unusually reliable and regular charcteristics can be secured. This is often very important medically, especially when treating patients having coronary diseases, as with nitroglycerin, or related problems of circulatory disorders such as angina pectoris or abnormal blood pressure conditions or psychotropic/manic-depressive schizophrenia. The invention is therefore of unusually versatile and adaptable nature giving it a wide scope of application and use.
The foregoing is exemplary of compositions and products responding to the present invention, but it is to be understood that they are illustrative and not limitative since many active ingredients of various types can be employed in the new long-lasting oral carrier provided they are absorbable in serum or tissue, the general intestinal tract, etc. The invention is also intended to cover other dosage forms or forms for application of sustained release ingredients such as vaginal and rectal suppositories. The total dosage is governed by usual medical considerations or physicians' directions and sufficiently large total doses of active medicament are administered in unit dosage tablet form containing from 10--500 milligrams to overcome or to control the pathological condition or disorder being treated. The presence of a stabilizing agent tends to prevent unwanted changes in moisture content by avoiding pick-up or loss of moisture due to climatic conditions of high or low humidity in tropical or arid geographical locations or shipping or storage variatioins. It is therefore a particular feature of this invention to add a stabilizer to the carrier material such as ascorbyl stearate or palmitate or an initiator such as sodium metabisulphite. The stabilizer is usually added after the carrier material is otherwise processed and in a small amount of the order of 0.11.0% of the weight of the carrier, preferably substantially 0.2%. The sodium metabisulphite (Na2 S205), a Redox Initiator for the copolymer, permits copolymerization to be carried out rapidly during humidification. The sodium metabisulphite is employed for this purpose in a concentration of 0.1% of the total weight of the polymer (hydroxypropylmethylcellulose) used.
In evaluating drugs incorporated in the oral carrier system or base of the present invention, it is important to understand the factors influencing the absorption and therapeutic effectiveness of drug products in compositions responding hereto. Under usual circumstances, the disintegration of a tablet into small particles in the gastrointestinal fluids speeds dissolution because of much increased surface area of the drug.
Consequently absorption is more rapid and the duration of therapeutic action depends primarily upon the rate of absorption. The rate and extent of drug absorption can thus influence both the duration of action and efficacy of drug therapy. It follows that the faster the absorption the earlier the peak level of the drug is reached, but, if absorption is too slow, the concentration of the drug in blood and tissues may never reach therapeutic levels. Subsequent to absorption, there is a drop in concentration that depends in large part upon elimination and/or metabolization.
Drugs embedded in the present
"Synchron" Carrier System, as I term the carrier base, are intended to attain and to maintain a steady concentration of drug in blood or tissues. One objective in using these preparations is to reduce the dosage frequency, to make therapy simple and convenient, and to improve compliance by the patient. In addition, by maintaining a reasonably constant plasma concentration of drug, excessive or premature peaking is avoided and side-effects, which may be associated with peak concentrations of drug, are lessened. In addition, a more uniform concentration of drug in blood and tissues is much more likely to be paralleled by a more uniform pharmacological effect and response. With dissolution being the main rate-limiting step in drug absorption, the rate of solution of the drug from the dosage form into the surrounding fluids at the absorption site is controlled by the physical technique employed in the production of the "Synchron" Carrier
System. With the "Synchron" Carrier
System the drug can further be released to a specific site at a uniform rate independently of the pH environment, resulting in steady concentrations of the drug in tissues. Drugs incorporated into the "Synchron" Carrier
System vehicle are prone to be absorbed completely, but more slowly, and are formulated to maintain the therapeutic effective level of the particular drug and to produce a prolonged response and a diminished rate of unassimilated drug elimination.
The absorption data may be determined and expressed as the cumulative percentage of the dose absorbed plotted against time or analysed further to derive information as to the kinetics of the absorption process.
Usually, the total body clearance of a drug is fixed.Accordingly, the total area under the plasma concentration-time curve is props -ional to the dose absorbed and independent of the rate of absorption. Area analysis forms the basis for estimation and comparison of the extent of absorption when the same dose is given in different dosage forms or by different routes of administration, or in different carrier systems. The "Synchron" Carrier System has the added advantage compared with other available prolonged-release vehicles employed in dosage forms that it will not release the drug in a dumping action and prevents the potential hazard of overdosage if all the drug is released at one tirne and is rapidly absorbed. The potency for determining a sustaining dose with the present carrier system may be expressed by the formula:
D x 0.693 x SV/L112 wherein D is the normal therapeutic dose,
SV is the number of hours desired to extend the duration of action, and L112 is the drug's half-life.
The primary difference between the use of my "Synchron" Carrier System and other sustained-release vehicles is that the hydrolysis or digestion of the vehicle is not dependent upon the pH or the enzymatic activity of the intestinal fluids. Via the concentration of the vehicle in the dosage form site action predetermination is possible.
WHAT I CLAIM IS: 1. A shaped and compressed sustained release therapeutic composition which comprises a carrier base material of hydroxypropylmethylcellulose or of a mixture of hydroxypropylmethylcellulose and up to 20% by weight ethylcellulose which hydroxypropylmethylcellulose or mixture has been humidified to a moisture content of at least 85% by weight and then dehumidified to a moisture content of 210% by weight while in powder form, and a systemically active medicament incorporated therein, the carrier and medicament being compressed and shaped.
2. A composition as claimed in claim 1, in which the hydroxypropylmethylcellulose treated carrier material has a carbonyl content of 0.92 1.43 grams/100 grams and a carboxyl content of 0.54.57 grams/100 grams.
3. A composition according to claim 1 or 2, in which the carrier base material contains 10(#80% hydroxypropylethylcellulose and 020% ethylcellulose, by weight.
4. A composition according to any of claims 1 to 3 compressed into tablet shape at a pressure of 7 to 13kg/square inch.
5. A compressed tablet according to any of claims 1 to 4, in which the active medicament is nitroglycerin or amyl nitrite.
6. A compressed tablet according to any of claims 1 to 4, in which the active medicament is prednisolone.
7. A compressed tablet according to any of claims 1 to 4, in which the active medicament is ampicillin.
8. A compressed tablet according to any of claims 1 to 4, in which the active medicament is amoxycillin.
9. A compressed tablet according to any of claims 1 to 4, in which the active medicament is cephalothin, cephalexin or cephaloglycine.
10. A compressed tablet according to any of claims 1 to 4, in which the active medicament is lithium carbonate.
11. A compressed tablet according to any of claims 1 to 4, in which the active medicament is tetracycline.
12. A composition according to any of claims 1 to 11 which contains an effective amount of an active medicament which is released after ingestion over a period of time and at a rate related to the size of the tablet and the degree of its compression.
13. A therapeutic composition as claimed in any of claims 1 to 12 which also includes a stabilizing agent.
14. A method of producing a sustained release tablet containing a systemically active ingredient effective over a predetermined period of time and at a rate related to the size and degree of compression of the tablet, which comprises humidifying hydroxypropylmethylcellulose or a mixture of hydroxypropylmethylcellulose with up to 20% by weight ethylcellulose to a moisture content of substantially 85% by weight while in powder form, and dehumidifying the resulting material at elevated temperature until its moisture content is stabilized in the range of 210%, by weight, and tableting the thus treated material after admixture with the systemically active ingredient.
15. A method according to claim 14, wherein the moisture content is reduced to 4.5-5.5%.
16. A method according to claim 14 or 15, wherein a stabilizing agent is added.
17. A method according to any of claims 14 to 16, wherein copolymerization during humidification is carried out with the addition of sodium metabisulphite.
18. A method according to claim 17, wherein copolymerization during humidification is carried out with the addition of sodium metabisulphite in a concentration of 0.1% of the total weight of the polymer.
19. A carrier base material for use in sustained release therapeutic compositions, the material comprising hydroxpropylmethylcellulose and up to 20% by weight ethylcellulose, which material has been humidified to a moisture content of at least 85% by weight, and then dehumidified to a mositure content of 210% by weight while in powder form.
20. A carrier base material according to claim 19, in which the humidified material is de-humidified to a moisture content in the range of 4.55.5% by weight.
21. A therapeutic composition according to claim 1, substantially as herein described witch reference to any of the specific Examples.
22. A method according to claim 14 substantially as herein described.
23. A carrier base material according to claim 19 substantially as herein described.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (23)
1. A shaped and compressed sustained release therapeutic composition which comprises a carrier base material of hydroxypropylmethylcellulose or of a mixture of hydroxypropylmethylcellulose and up to 20% by weight ethylcellulose which hydroxypropylmethylcellulose or mixture has been humidified to a moisture content of at least 85% by weight and then dehumidified to a moisture content of 210% by weight while in powder form, and a systemically active medicament incorporated therein, the carrier and medicament being compressed and shaped.
2. A composition as claimed in claim 1, in which the hydroxypropylmethylcellulose treated carrier material has a carbonyl content of 0.92 1.43 grams/100 grams and a carboxyl content of 0.54.57 grams/100 grams.
3. A composition according to claim 1 or 2, in which the carrier base material contains 10(#80% hydroxypropylethylcellulose and 020% ethylcellulose, by weight.
4. A composition according to any of claims 1 to 3 compressed into tablet shape at a pressure of 7 to 13kg/square inch.
5. A compressed tablet according to any of claims 1 to 4, in which the active medicament is nitroglycerin or amyl nitrite.
6. A compressed tablet according to any of claims 1 to 4, in which the active medicament is prednisolone.
7. A compressed tablet according to any of claims 1 to 4, in which the active medicament is ampicillin.
8. A compressed tablet according to any of claims 1 to 4, in which the active medicament is amoxycillin.
9. A compressed tablet according to any of claims 1 to 4, in which the active medicament is cephalothin, cephalexin or cephaloglycine.
10. A compressed tablet according to any of claims 1 to 4, in which the active medicament is lithium carbonate.
11. A compressed tablet according to any of claims 1 to 4, in which the active medicament is tetracycline.
12. A composition according to any of claims 1 to 11 which contains an effective amount of an active medicament which is released after ingestion over a period of time and at a rate related to the size of the tablet and the degree of its compression.
13. A therapeutic composition as claimed in any of claims 1 to 12 which also includes a stabilizing agent.
14. A method of producing a sustained release tablet containing a systemically active ingredient effective over a predetermined period of time and at a rate related to the size and degree of compression of the tablet, which comprises humidifying hydroxypropylmethylcellulose or a mixture of hydroxypropylmethylcellulose with up to 20% by weight ethylcellulose to a moisture content of substantially 85% by weight while in powder form, and dehumidifying the resulting material at elevated temperature until its moisture content is stabilized in the range of 210%, by weight, and tableting the thus treated material after admixture with the systemically active ingredient.
15. A method according to claim 14, wherein the moisture content is reduced to 4.5-5.5%.
16. A method according to claim 14 or 15, wherein a stabilizing agent is added.
17. A method according to any of claims 14 to 16, wherein copolymerization during humidification is carried out with the addition of sodium metabisulphite.
18. A method according to claim 17, wherein copolymerization during humidification is carried out with the addition of sodium metabisulphite in a concentration of 0.1% of the total weight of the polymer.
19. A carrier base material for use in sustained release therapeutic compositions, the material comprising hydroxpropylmethylcellulose and up to 20% by weight ethylcellulose, which material has been humidified to a moisture content of at least 85% by weight, and then dehumidified to a mositure content of 210% by weight while in powder form.
20. A carrier base material according to claim 19, in which the humidified material is de-humidified to a moisture content in the range of 4.55.5% by weight.
21. A therapeutic composition according to claim 1, substantially as herein described witch reference to any of the specific Examples.
22. A method according to claim 14 substantially as herein described.
23. A carrier base material according to claim 19 substantially as herein described.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US68341076A | 1976-05-05 | 1976-05-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1583801A true GB1583801A (en) | 1981-02-04 |
Family
ID=24743943
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8515/77A Expired GB1583801A (en) | 1976-05-05 | 1977-05-01 | Oral carrier base its preparation and dosage units made therefrom |
Country Status (10)
Country | Link |
---|---|
JP (1) | JPS5817445B2 (en) |
BR (1) | BR7702882A (en) |
CA (1) | CA1103161A (en) |
DE (1) | DE2718260C2 (en) |
FR (1) | FR2358895A1 (en) |
GB (1) | GB1583801A (en) |
IL (1) | IL50175A0 (en) |
MX (1) | MX4545E (en) |
SE (1) | SE7704764L (en) |
YU (1) | YU43437B (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4680323A (en) * | 1983-12-01 | 1987-07-14 | Hans Lowey | Method and composition for the preparation of controlled long-acting pharmaceuticals for oral administration |
US4775535A (en) * | 1986-04-04 | 1988-10-04 | Hans Lowey | Method of preparing controlled long-acting pharmaceutical formulations in unit dosage form having uniform and comparable bioavailability characteristics |
US4855143A (en) * | 1986-04-04 | 1989-08-08 | Hans Lowey | Method of preparing controlled long-acting pharmaceutical formulations in unit dosage form having uniform and comparable bioavailability characteristics |
US5437872A (en) * | 1989-08-25 | 1995-08-01 | Bioglan Laboratories Ltd. | Pharmaceutical compositions and a device for administering the same |
US5948437A (en) * | 1996-05-23 | 1999-09-07 | Zeneca Limited | Pharmaceutical compositions using thiazepine |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2042888B (en) * | 1979-03-05 | 1983-09-28 | Teijin Ltd | Preparation for administration to the mucosa of the oral or nasal cavity |
JPS6034925B2 (en) * | 1979-07-31 | 1985-08-12 | 帝人株式会社 | Long-acting nasal preparation and its manufacturing method |
US4259314A (en) | 1979-12-10 | 1981-03-31 | Hans Lowey | Method and composition for the preparation of controlled long-acting pharmaceuticals |
US4369172A (en) * | 1981-12-18 | 1983-01-18 | Forest Laboratories Inc. | Prolonged release therapeutic compositions based on hydroxypropylmethylcellulose |
JPS59501162A (en) * | 1982-06-24 | 1984-07-05 | キイ・フア−マシユ−テイカルズ・インコ−ポレイテツド | Extended release propranolol tablets |
JPS59193831A (en) * | 1983-04-18 | 1984-11-02 | Sankyo Co Ltd | Preparation of enteric drug |
JPH07112934A (en) * | 1993-10-15 | 1995-05-02 | Taiyo Yakuhin Kogyo Kk | Sustained release preparation of pentoxyphylline and its production |
US6099859A (en) | 1998-03-20 | 2000-08-08 | Andrx Pharmaceuticals, Inc. | Controlled release oral tablet having a unitary core |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3065143A (en) * | 1960-04-19 | 1962-11-20 | Richardson Merrell Inc | Sustained release tablet |
AU452221B2 (en) * | 1971-09-20 | 1974-08-09 | Forest Laboratories, Inc. | Long-acting oral carrier |
GB1388786A (en) * | 1972-04-03 | 1975-03-26 | Scherer Corp R P | Integral solid gel-lattice dosage form of high-moisture content |
US3965256A (en) * | 1972-05-16 | 1976-06-22 | Synergistics | Slow release pharmaceutical compositions |
CA1018456A (en) * | 1972-06-26 | 1977-10-04 | Hans Lowey | Prolonged release lozenges |
-
1976
- 1976-07-26 YU YU1841/76A patent/YU43437B/en unknown
- 1976-07-30 IL IL50175A patent/IL50175A0/en unknown
-
1977
- 1977-03-25 FR FR7709055A patent/FR2358895A1/en active Granted
- 1977-04-20 CA CA276,537A patent/CA1103161A/en not_active Expired
- 1977-04-25 DE DE2718260A patent/DE2718260C2/en not_active Expired
- 1977-04-26 SE SE7704764A patent/SE7704764L/en unknown
- 1977-04-28 JP JP52049778A patent/JPS5817445B2/en not_active Expired
- 1977-05-01 GB GB8515/77A patent/GB1583801A/en not_active Expired
- 1977-05-04 BR BR2882/77A patent/BR7702882A/en unknown
- 1977-05-04 MX MX775718U patent/MX4545E/en unknown
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4680323A (en) * | 1983-12-01 | 1987-07-14 | Hans Lowey | Method and composition for the preparation of controlled long-acting pharmaceuticals for oral administration |
US4775535A (en) * | 1986-04-04 | 1988-10-04 | Hans Lowey | Method of preparing controlled long-acting pharmaceutical formulations in unit dosage form having uniform and comparable bioavailability characteristics |
US4855143A (en) * | 1986-04-04 | 1989-08-08 | Hans Lowey | Method of preparing controlled long-acting pharmaceutical formulations in unit dosage form having uniform and comparable bioavailability characteristics |
US5437872A (en) * | 1989-08-25 | 1995-08-01 | Bioglan Laboratories Ltd. | Pharmaceutical compositions and a device for administering the same |
US5948437A (en) * | 1996-05-23 | 1999-09-07 | Zeneca Limited | Pharmaceutical compositions using thiazepine |
Also Published As
Publication number | Publication date |
---|---|
JPS5817445B2 (en) | 1983-04-07 |
YU184176A (en) | 1984-02-29 |
SE7704764L (en) | 1977-11-06 |
IL50175A0 (en) | 1976-09-30 |
FR2358895B1 (en) | 1982-10-22 |
YU43437B (en) | 1989-08-31 |
JPS52145514A (en) | 1977-12-03 |
BR7702882A (en) | 1978-01-31 |
DE2718260A1 (en) | 1977-11-17 |
DE2718260C2 (en) | 1983-08-11 |
MX4545E (en) | 1982-06-10 |
CA1103161A (en) | 1981-06-16 |
FR2358895A1 (en) | 1978-02-17 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed [section 19, patents act 1949] | ||
PE20 | Patent expired after termination of 20 years |
Effective date: 19970430 |