CA1157776A - Directly compressible acetaminophen granulation - Google Patents
Directly compressible acetaminophen granulationInfo
- Publication number
- CA1157776A CA1157776A CA000392780A CA392780A CA1157776A CA 1157776 A CA1157776 A CA 1157776A CA 000392780 A CA000392780 A CA 000392780A CA 392780 A CA392780 A CA 392780A CA 1157776 A CA1157776 A CA 1157776A
- Authority
- CA
- Canada
- Prior art keywords
- acetaminophen
- granulation
- weight
- lubricant
- nacmc
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
-
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Abstract
Abstract of the Disclosure Free flowing granulation, comprising a high concentration of acetaminophen and a low level of excip-ient, including ground cross-linked sodium carboxy-methylcellulose fiber, allows the manufacture of anal-gesic tables by direct compression. The method pro-vides improvements in manufacturing economics and tablet properties.
Description
DIRECTLY COMPRESSIBLE ACETAMINOPHEN
GRANULATION
Background of the Invention This invention relates to the preparation of tablets comprising acetaminophen. In general, there are four principle methods widely used in the United States for tablet manufacture. The four methods are:
- Direct Compression - In this method, all re-quired tableting aids are incorporated in a free flowing granulation as supplied by the bulk - analgesic manufacturer. The granulation re-quires no pre-processing, or blending with additional aids, and is charged directly to a tableting press. This method is used extensively in the manufacture of generic aspirin tablets.
- Dry Powder Blend - In this method all required tableting aids are blended with crystal grade acetaminophen or aspirin. The blend is then charged directly to a tableting press. Gelatin or polyvinylpyrrolidone coated acetaminophen powder is sometimes used in place of crystal grade acetaminophen.
- Pre-Compressed Dry Powder Blend - In this method the dry powder blend containing all required tableting aids -is pre-compressed either by roll compaction or slugging. Roll compaction is the most popular method of preparing granulated ~$
GRANULATION
Background of the Invention This invention relates to the preparation of tablets comprising acetaminophen. In general, there are four principle methods widely used in the United States for tablet manufacture. The four methods are:
- Direct Compression - In this method, all re-quired tableting aids are incorporated in a free flowing granulation as supplied by the bulk - analgesic manufacturer. The granulation re-quires no pre-processing, or blending with additional aids, and is charged directly to a tableting press. This method is used extensively in the manufacture of generic aspirin tablets.
- Dry Powder Blend - In this method all required tableting aids are blended with crystal grade acetaminophen or aspirin. The blend is then charged directly to a tableting press. Gelatin or polyvinylpyrrolidone coated acetaminophen powder is sometimes used in place of crystal grade acetaminophen.
- Pre-Compressed Dry Powder Blend - In this method the dry powder blend containing all required tableting aids -is pre-compressed either by roll compaction or slugging. Roll compaction is the most popular method of preparing granulated ~$
-2-aspirin. A homogenous blend of aspirin and starch is roll compacted, milled, sifted and drummed. The granulated product is charged directly to a tableting press.
- Wet Granulation - This is the most popular method of granulating acetaminophen. In this method acetaminophen crystal or powder is blended with intragranular excipients, then wetted to a moist powder consistency with an aqueous binder solution. In some cases the powder is wetted to a dough consistency and forced through a 10-14 mesh screen. The wetted mass is then dried by conventional means, milled, sifted, and blended with extragranular excipients and lubricant. This mixture is then fed to a tableting press.
Acetaminophen is not ordinarily amenable to tableting by the same methods as aspirin. These materials have significantly different properties.
Thus, crystalline aspirin is easily tableted, since the crystals are quite soft and exhibit good plasticity/
elasticity when compacted to tablets. Further, cohesive/
adhesive bonding within the aspirin tablet is strong and the aspirin, itself, provides good lubricity to the formula. Accordingly, no lubricant is necessary in the formula used for aspirin tableting. In contrast, acetaminophen crystals are very hard and brittle and fracture very easily. The crystals have essentially no plasticity/elasticity and can be tableted by the normal aspirin tableting methods only by using high levels of excipients and large crystalline grade acet-aminophen~ Furthermore, at least 25% or more excip-ients are required in addition to high levels of lubri-cant. The large acetaminophen crystals have the dis-advantage of being slowly dissolved in the body and require additional tableting aids to increase the rate 1 1~777~
of dissolution.
Accordingly, acetaminophen has been prefer-ably tableted using the wet granulation method since the direct compression method, the dry powder blending method and the pre-compression method have not been shown to be amenable in acetaminophen tableting for the reasons noted above.
The direct compression method of preparing tablets would be the method of choice for preparing acetaminophen tablets if a formulation comprising acetaminophen could be prepared which would allow the use of such method. Accordingly, there is a need for an acetaminophen formulation containing all required tableting aids which may be used in direct compression tableting.
Summary of the Invention It is an object of this invention to provide a formulation comprising acetaminophen which is directly compressible to tablets.
It is a further object of this invention to provide an acetaminophen tablet which is prepared by a direct compression method.
The above objects of this invention are achieved by the process and formulation of the present invention, whereby an acetaminophen formulation having a low excipient level is provided which thereby allows economics in manufacture, because of the high cost of excipients, and the ability to prepare a smaller tablet having the same dosage of acetaminophen as larger tablets prepared by other methods. Further,the costly and tedious process of wet granulating is elim-inated.
Although direct compression aspirin granula-tion is extensively used to prepare aspirin tablets, a similar formula and granulating process are not directly 1 15777~
convertible to granulating acetaminophen because of the difference in characteristics between aspirin and acet-aminophen. The present invention describes a formula and process which affords manufacture of direct com-pression acetaminophen granulation having similar excip-ient level and tableting characteristics as direct compression aspirin granulation. Excellent quality acetaminophen tablets having a high concentration of acetaminophen are attained by the direct compression method. Further, the granulation and tablets afforded by this invention are stable and non-pinking. The granulation is tabletable at a wide range of pressures providing tablets having remarkably rapid disintegra-tion and dissolution features.
The uniqueness of the acetaminophen granula-tions of the present invention is due to the following considerations: (1) all excipients are incorporated in the granulation. No further addition of excipients is necessary for tableting. (2) the granulation 2~ contains a high, i.e. 80-90 wt. ~, concentrat~.on of active analgesic agent, i.e. acetaminophen and (3) the granulation requires no pre-processing prior to tableting.
In general, the method of preparing the acet-aminophen granulation of the invention comprises charging acetaminophen powder and other ingredients to be used in the tablet to a fluidizer, fluidizing the mixture with warm air while spraying the mixture with an aqueous starch slurry, drying the mixture, adding lubricant and mixing the ingredients to uniformity.
Preferred Embodiments of the Invention In accordance with the present invention, it has been found that an acetaminophen formulation con-taining ground cross-linked sodium carboxymethylcellulose (NaCMC) fiber allows tableting of the acetaminophen formulation by the direct compression method, a method which has heretofore been unavailable for the tablet-ing of acetaminophen formulations. The formulation comprising acetaminophen and ground NaCMC fiber pro-vides superior quality tablets with respect to fri-ability, dissolution, disintegration and tablet aesthetics.
Typically, prior acetaminophen granulations used for preparing tablets by the wet granulation method contained approximately 25-40% excipients.
Commonly used excipients include binders such as gelatin, polyvinylpyrrolidone, and gelatinized starch, disintegrants such as corn starch and microcrystalline cellulose, glidants such as silica, talc, and corn - starch, and lubricants such as stearic acid and stearate salts, e.g. magnesium stearate.
In contrast to the prior methods of tableting acetaminophen granulations, the process and granula-tion of the present invention allows the preparation of acetaminophen tablets containing 80-90% acetaminophen.
The unique qualities of the granulation of the present invention are attributable to the use of ground NaCMC fiber during the fluidized bed granulation, thereby allowing the higher percentages of acetaminophen in the granulation and still achieving high quality tablets.
In general, the granulations of the present invention comprise from about 80 to about 90% by weight acetaminophen, from about 0.1 to about 5.0% by weight ground NaCMC fiber, from about 1.0 to about 15.0% by weight pregelatinized starch, from about 0.1 to about 2.0% by weight lubricant, e.g. stearic acid or magnesium stearate. Alternative or additional excipients may include a binder, e.g. purified wood fiber; a disinte-grant, e.g. sodium starch glycolate; an antioxidant, e.g. sodium metabisulfite; a preservative, e.g. propyl-paraben; a surfactant, e.g. alkali metal salts of high molecular weight alkyl sulfates or sulfonates and similar materials of like nature.
A typical preferred formula useful for gran-ulation in accordance with the present invention, itsmethod of preparation and the properties of the tablets obtained thereby as compared to commercial tablets are set forth in the following example and Table 1.
Example The following formula is utilized in this example:
Table 1 Ingredient Weight %
Milled Acetaminophen 90.0 Ground NaCMC Fi~er 3.50 Pregelatinized Starch 6.00 Stearic Acid 0-50 The above formulation is granulated in a fluidized bed granulator. The granulating conditions utilizing the formula are as follows:
6300 grams of milled acetaminophen and 245 grams ground NaCMC fiber are charged to the granulator and fluidized for about 2 to 5 minutes in order to homogenize the ingredients. A dispersion is then pre-pared utilizing 420 grams pregelationized starch in5,580 grams water via vigorous agitation. While mixing, the suspension is warmed to about 85C. to effect gelling. The mixture is cooled and maintained at 60-70C.
Agitation is maintained to avoid film formation on the surface. Just prior to use, 1.6 grams sodium meta-bisulfite dissolved in 50 ml water is introduced and mixed into the starch suspension. The dispersion is atomized onto the fluidized acetaminophen/ground NaCMC
fiber over a period of 30-90 minutes under typical granulating conditions of air flow rate, temperature and spray nozzle parameters. When binder addition is completed, the batch is dried by continued fluidization with warmair to a moisture level of 0.7 to 1.5%.
Magnesium stearate or stearic acid is added and blended into the product by fluidization for 1 to 5 minutes with ambient temperature air.
Although a 10% excipient level is shown in the above example, excipient levels of up to 20~ and even higher, e.g. 25-40~, can be selected so long as ground NaCMC fiber is present in a range of about 0.1 to about 5.0% by weight. Other tableting aids and con-centrations thereof besides those listed in thq example can also be selected. Other acceptable binder solutions lS which can be used are solutions of gelatin, polyvinyl-pyrrolidone, polyethylene glycol or mixtures thereof separately or admixed with gelatinous starch or other binders.
- Wet Granulation - This is the most popular method of granulating acetaminophen. In this method acetaminophen crystal or powder is blended with intragranular excipients, then wetted to a moist powder consistency with an aqueous binder solution. In some cases the powder is wetted to a dough consistency and forced through a 10-14 mesh screen. The wetted mass is then dried by conventional means, milled, sifted, and blended with extragranular excipients and lubricant. This mixture is then fed to a tableting press.
Acetaminophen is not ordinarily amenable to tableting by the same methods as aspirin. These materials have significantly different properties.
Thus, crystalline aspirin is easily tableted, since the crystals are quite soft and exhibit good plasticity/
elasticity when compacted to tablets. Further, cohesive/
adhesive bonding within the aspirin tablet is strong and the aspirin, itself, provides good lubricity to the formula. Accordingly, no lubricant is necessary in the formula used for aspirin tableting. In contrast, acetaminophen crystals are very hard and brittle and fracture very easily. The crystals have essentially no plasticity/elasticity and can be tableted by the normal aspirin tableting methods only by using high levels of excipients and large crystalline grade acet-aminophen~ Furthermore, at least 25% or more excip-ients are required in addition to high levels of lubri-cant. The large acetaminophen crystals have the dis-advantage of being slowly dissolved in the body and require additional tableting aids to increase the rate 1 1~777~
of dissolution.
Accordingly, acetaminophen has been prefer-ably tableted using the wet granulation method since the direct compression method, the dry powder blending method and the pre-compression method have not been shown to be amenable in acetaminophen tableting for the reasons noted above.
The direct compression method of preparing tablets would be the method of choice for preparing acetaminophen tablets if a formulation comprising acetaminophen could be prepared which would allow the use of such method. Accordingly, there is a need for an acetaminophen formulation containing all required tableting aids which may be used in direct compression tableting.
Summary of the Invention It is an object of this invention to provide a formulation comprising acetaminophen which is directly compressible to tablets.
It is a further object of this invention to provide an acetaminophen tablet which is prepared by a direct compression method.
The above objects of this invention are achieved by the process and formulation of the present invention, whereby an acetaminophen formulation having a low excipient level is provided which thereby allows economics in manufacture, because of the high cost of excipients, and the ability to prepare a smaller tablet having the same dosage of acetaminophen as larger tablets prepared by other methods. Further,the costly and tedious process of wet granulating is elim-inated.
Although direct compression aspirin granula-tion is extensively used to prepare aspirin tablets, a similar formula and granulating process are not directly 1 15777~
convertible to granulating acetaminophen because of the difference in characteristics between aspirin and acet-aminophen. The present invention describes a formula and process which affords manufacture of direct com-pression acetaminophen granulation having similar excip-ient level and tableting characteristics as direct compression aspirin granulation. Excellent quality acetaminophen tablets having a high concentration of acetaminophen are attained by the direct compression method. Further, the granulation and tablets afforded by this invention are stable and non-pinking. The granulation is tabletable at a wide range of pressures providing tablets having remarkably rapid disintegra-tion and dissolution features.
The uniqueness of the acetaminophen granula-tions of the present invention is due to the following considerations: (1) all excipients are incorporated in the granulation. No further addition of excipients is necessary for tableting. (2) the granulation 2~ contains a high, i.e. 80-90 wt. ~, concentrat~.on of active analgesic agent, i.e. acetaminophen and (3) the granulation requires no pre-processing prior to tableting.
In general, the method of preparing the acet-aminophen granulation of the invention comprises charging acetaminophen powder and other ingredients to be used in the tablet to a fluidizer, fluidizing the mixture with warm air while spraying the mixture with an aqueous starch slurry, drying the mixture, adding lubricant and mixing the ingredients to uniformity.
Preferred Embodiments of the Invention In accordance with the present invention, it has been found that an acetaminophen formulation con-taining ground cross-linked sodium carboxymethylcellulose (NaCMC) fiber allows tableting of the acetaminophen formulation by the direct compression method, a method which has heretofore been unavailable for the tablet-ing of acetaminophen formulations. The formulation comprising acetaminophen and ground NaCMC fiber pro-vides superior quality tablets with respect to fri-ability, dissolution, disintegration and tablet aesthetics.
Typically, prior acetaminophen granulations used for preparing tablets by the wet granulation method contained approximately 25-40% excipients.
Commonly used excipients include binders such as gelatin, polyvinylpyrrolidone, and gelatinized starch, disintegrants such as corn starch and microcrystalline cellulose, glidants such as silica, talc, and corn - starch, and lubricants such as stearic acid and stearate salts, e.g. magnesium stearate.
In contrast to the prior methods of tableting acetaminophen granulations, the process and granula-tion of the present invention allows the preparation of acetaminophen tablets containing 80-90% acetaminophen.
The unique qualities of the granulation of the present invention are attributable to the use of ground NaCMC fiber during the fluidized bed granulation, thereby allowing the higher percentages of acetaminophen in the granulation and still achieving high quality tablets.
In general, the granulations of the present invention comprise from about 80 to about 90% by weight acetaminophen, from about 0.1 to about 5.0% by weight ground NaCMC fiber, from about 1.0 to about 15.0% by weight pregelatinized starch, from about 0.1 to about 2.0% by weight lubricant, e.g. stearic acid or magnesium stearate. Alternative or additional excipients may include a binder, e.g. purified wood fiber; a disinte-grant, e.g. sodium starch glycolate; an antioxidant, e.g. sodium metabisulfite; a preservative, e.g. propyl-paraben; a surfactant, e.g. alkali metal salts of high molecular weight alkyl sulfates or sulfonates and similar materials of like nature.
A typical preferred formula useful for gran-ulation in accordance with the present invention, itsmethod of preparation and the properties of the tablets obtained thereby as compared to commercial tablets are set forth in the following example and Table 1.
Example The following formula is utilized in this example:
Table 1 Ingredient Weight %
Milled Acetaminophen 90.0 Ground NaCMC Fi~er 3.50 Pregelatinized Starch 6.00 Stearic Acid 0-50 The above formulation is granulated in a fluidized bed granulator. The granulating conditions utilizing the formula are as follows:
6300 grams of milled acetaminophen and 245 grams ground NaCMC fiber are charged to the granulator and fluidized for about 2 to 5 minutes in order to homogenize the ingredients. A dispersion is then pre-pared utilizing 420 grams pregelationized starch in5,580 grams water via vigorous agitation. While mixing, the suspension is warmed to about 85C. to effect gelling. The mixture is cooled and maintained at 60-70C.
Agitation is maintained to avoid film formation on the surface. Just prior to use, 1.6 grams sodium meta-bisulfite dissolved in 50 ml water is introduced and mixed into the starch suspension. The dispersion is atomized onto the fluidized acetaminophen/ground NaCMC
fiber over a period of 30-90 minutes under typical granulating conditions of air flow rate, temperature and spray nozzle parameters. When binder addition is completed, the batch is dried by continued fluidization with warmair to a moisture level of 0.7 to 1.5%.
Magnesium stearate or stearic acid is added and blended into the product by fluidization for 1 to 5 minutes with ambient temperature air.
Although a 10% excipient level is shown in the above example, excipient levels of up to 20~ and even higher, e.g. 25-40~, can be selected so long as ground NaCMC fiber is present in a range of about 0.1 to about 5.0% by weight. Other tableting aids and con-centrations thereof besides those listed in thq example can also be selected. Other acceptable binder solutions lS which can be used are solutions of gelatin, polyvinyl-pyrrolidone, polyethylene glycol or mixtures thereof separately or admixed with gelatinous starch or other binders.
Claims (15)
1. A directly compressible analgesic gran-ulation comprising from about 80% to about 90% by weight acetaminophen, from about 0.1% to about 5.0% by weight ground NaCMC fiber, from about 1.0% to about 15.0% binder and from about 0.1% to about 2.0% by weight lubricant.
2. Granulation of Claim 1 which contains about 80% by weight acetaminophen.
3. Granulation of Claim 1 which contains about 85% by weight acetaminophen.
4. Granulation of Claim 1 which contains about 90% by weight acetaminophen.
5. Granulation of Claim 1 which contains about 3.5% by weight NaCMC fiber.
6. Granulation of Claim 1 wherein said binder is pregelatinized starch.
7. Granulation of Claim 6 wherein said starch is present in an amount of about 6% by weight.
8. Granulation of Claim 1 wherein said lubricant is selected from the group consisting of stearic acid and magnesium stearate.
9. Granulation of Claim 8 wherein said lubricant is present in an amount of about 0.5% by weight.
10. A directly compressible analgesic gran-ulation comprising about 90% by weight acetaminophen, about 3.5% by weight ground NaCMC, about 6% by weight pregelatinized starch and about 0.5% stearic acid.
11. An analgesic tablet comprising the gran-ulation of Claim 1.
12. An analgesic tablet comprising the gran-ulation of Claim 10.
13. A method of preparing an analgesic gran-ulation which comprises admixing acetaminophen and ground NaCMC fiber in a granulator and fluidizing same, forming a dispersion of binder in water and atomizing said dispersion onto said fluidized admixture, drying same by continued fluidization in the presence of heated air and adding thereto a lubricant.
14. Method of Claim 13 wherein said binder is pregelatinized starch.
15. Method of Claim 1 wherein said lubricant is stearic acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21929080A | 1980-12-22 | 1980-12-22 | |
| US219,290 | 1980-12-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1157776A true CA1157776A (en) | 1983-11-29 |
Family
ID=22818680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000392780A Expired CA1157776A (en) | 1980-12-22 | 1981-12-21 | Directly compressible acetaminophen granulation |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS57130913A (en) |
| AR (1) | AR226763A1 (en) |
| AU (1) | AU545475B2 (en) |
| BE (1) | BE891557A (en) |
| CA (1) | CA1157776A (en) |
| DE (1) | DE3150557A1 (en) |
| FR (1) | FR2496461B1 (en) |
| GB (1) | GB2090739B (en) |
| MY (1) | MY8600144A (en) |
| PH (1) | PH18488A (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4600579A (en) * | 1983-06-07 | 1986-07-15 | Mallinckrodt, Inc. | N-acetyl-p-aminophenol compositions containing partially gelatinized starch and method for preparing same |
| US4661521A (en) * | 1984-04-30 | 1987-04-28 | Mallinckrodt, Inc. | Direct tableting acetaminophen compositions |
| JPS61145111A (en) * | 1984-12-20 | 1986-07-02 | Lion Corp | Production of tablet |
| US4757090A (en) * | 1986-07-14 | 1988-07-12 | Mallinckrodt, Inc. | Direct tableting acetaminophen compositions |
| DE3636209A1 (en) * | 1986-10-24 | 1988-04-28 | Lentia Gmbh | METHOD FOR PRODUCING A BINDER-FREE TABLET-TABLE CELIPROLOL HYDROCHLORIDE GRANULATE |
| IE61676B1 (en) * | 1987-07-08 | 1994-11-30 | American Home Prod | Spray dried ibuprofen composition |
| JP2804048B2 (en) * | 1987-09-11 | 1998-09-24 | イー・アール・スクイブ・アンド・サンズ・インコーポレイテッド | High drug content pharmaceutical composition and method for producing the same |
| FR2638971B1 (en) * | 1988-11-15 | 1993-01-08 | Vacher Dominique | INSTANTLY AND / OR INSTANT DISSOLUTION TABLET |
| FR2672212B1 (en) * | 1991-02-04 | 1993-05-28 | Lille Ii Universite | PARACETAMOL CRYSTALS FOR DIRECT COMPRESSION, PROCESS FOR PREPARING SUCH CRYSTALS, AND TABLET OBTAINED WITH SUCH CRYSTALS. |
| JPH0656659A (en) * | 1992-06-10 | 1994-03-01 | Natl Sci Council | Pharmaceutical composition which can be directly made into tablet and preparation of said tablet |
| DE4327462A1 (en) * | 1993-08-16 | 1995-02-23 | Carl Heinrich Dr Weischer | N-Acetyl-p-aminophenol derivatives for controlling pain |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1390032A (en) * | 1971-08-27 | 1975-04-09 | Sterling Winthrop Group Ltd | Pharmaceutical compositions |
| JPS535725B2 (en) * | 1973-03-05 | 1978-03-01 | ||
| US3873694A (en) * | 1973-09-27 | 1975-03-25 | Cpc International Inc | Direct compression tabletting composition and pharmaceutical tablets produced therefrom |
| US4097606A (en) * | 1975-10-08 | 1978-06-27 | Bristol-Myers Company | APAP Tablet containing an alkali metal carboxymethylated starch and processes for manufacturing same |
| JPS5344618A (en) * | 1976-10-04 | 1978-04-21 | Takeda Chem Ind Ltd | Preparation of tablet |
| DE2713197A1 (en) * | 1977-03-25 | 1978-10-05 | Bayer Ag | Paracetamol spray dried granulate - contg. 0.5-3 wt. per cent polyvinyl-pyrrolidone and less than 0.3 per cent water |
-
1981
- 1981-12-18 AR AR287856A patent/AR226763A1/en active
- 1981-12-21 CA CA000392780A patent/CA1157776A/en not_active Expired
- 1981-12-21 JP JP56206798A patent/JPS57130913A/en active Granted
- 1981-12-21 PH PH26660A patent/PH18488A/en unknown
- 1981-12-21 DE DE19813150557 patent/DE3150557A1/en active Granted
- 1981-12-21 GB GB8138417A patent/GB2090739B/en not_active Expired
- 1981-12-21 AU AU78720/81A patent/AU545475B2/en not_active Expired
- 1981-12-21 FR FR8123864A patent/FR2496461B1/en not_active Expired
- 1981-12-21 BE BE0/206891A patent/BE891557A/en not_active IP Right Cessation
-
1986
- 1986-12-30 MY MY144/86A patent/MY8600144A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB2090739A (en) | 1982-07-21 |
| FR2496461B1 (en) | 1985-07-12 |
| BE891557A (en) | 1982-06-21 |
| PH18488A (en) | 1985-08-02 |
| MY8600144A (en) | 1986-12-31 |
| DE3150557C2 (en) | 1991-10-02 |
| JPH044297B2 (en) | 1992-01-27 |
| JPS57130913A (en) | 1982-08-13 |
| AU7872081A (en) | 1982-07-01 |
| AU545475B2 (en) | 1985-07-18 |
| FR2496461A1 (en) | 1982-06-25 |
| GB2090739B (en) | 1984-09-19 |
| DE3150557A1 (en) | 1982-09-02 |
| AR226763A1 (en) | 1982-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4439453A (en) | Directly compressible acetaminophen granulation | |
| EP1231911B1 (en) | Directly compressible, ultra fine acetaminophen compositions and process for producing same | |
| US5830576A (en) | Solid dosage forms | |
| CA1315202C (en) | Oral sustained release acetaminophen formulation and process | |
| US5104648A (en) | High ibuprofen content granulations | |
| KR100618038B1 (en) | Process for forming solid oral dosage of valsartan | |
| KR100642976B1 (en) | Tablets quickly disintegrating in the oral cavity and process for producing the same | |
| EP0689841B1 (en) | Powder preparation for healing damaged skin | |
| US5370878A (en) | Method for preparing a direct compression granulated acetaminophen composition | |
| CA1157776A (en) | Directly compressible acetaminophen granulation | |
| EP0456720B1 (en) | High ibuprofen content granulations | |
| EP0377658A1 (en) | A free-flowing granular composition containing ibuprofen and a method for its preparation. | |
| US4839176A (en) | Therapeutic agents | |
| JPH0696523B2 (en) | Granular N-acetyl-P-aminophenol composition and method for producing the same | |
| JP4709379B2 (en) | Pharmaceutical formulation containing levothyroxine sodium | |
| US5322698A (en) | Process for the preparation of a tablet or dragee composition containing a heat-, light- and moisture-sensitive active ingredient having monoclinic crystal structure | |
| US5037658A (en) | Direct dry compressible acetaminophen composition | |
| JP4280074B2 (en) | Multiple unit type sustained release tablets | |
| JP4293572B2 (en) | Loxoprofen sodium-containing tablets | |
| JPH08310969A (en) | Solid pharmaceutical composition and its preparation | |
| JPH1059842A (en) | Composition for tablet and making tablet | |
| AU611740B2 (en) | Pharmaceutical composition and process for its preparation | |
| US5130140A (en) | Method of making direct dry compressible acetaminophen composition | |
| SK18582000A3 (en) | Cyclophosphamide coated tablets | |
| DE3045488A1 (en) | Stabilised kallikrein contg. tablets prodn. - by mixing enzyme with sugar etc. soln., freeze drying blending with granular premix and compressing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry | ||
| MKEX | Expiry |
Effective date: 20001129 |