Continuous preparation of solid pharmaceutical forms

• US 5,073,379 A
• Filed: 08/25/1989
• Issued: 12/17/1991
• Est. Priority Date: 09/07/1988
• Status: Expired due to Fees

• Current Assignee: BASF Coatings GmbH (BASF SE)
• Original Assignee: BASF AG (BASF SE)
• Inventors: Sanner, Axel, Farwerck, Karl-Peter, Klimesch, Roger, Schlemmer, Lothar, Bleckmann, Gerhard
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US07/398,663
• Time in Patent Office: 844 Days
• Field of Search: 424/465, 424/467, 424/441, 424/440, 425/407
• US Class Current: 424/467
• CPC Class Codes: A61J 2200/20 Extrusion means, e.g. for producing pharmaceutical forms
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: B30B 11/14 co-operating with moulds on a movable carrier other than a turntable or a rotating drum
• CPC Class Codes: B30B 11/16 using pocketed rollers, e.g. two co-operating pocketed rollers

Abstract

A mixture of one or more pharmaceutical active compounds and one or more thermoplastic polymers is tabletted by a process in which the mixture is extruded and the still moldable extrudate is pressed to give tablets, between two belts, or a belt and a roller, which make contact in parts, rotate in opposite directions and run parallel along the contact zone, the shape-imparting indentations, which may be present in complementary pairs, being located in both or in only one of the revolving shape-imparting elements.

Claims

1. A process for tabletting a mixture of

one or more pharmaceutical active compounds,

one or more pharmacologically acceptable thermoplastic polymers, said polymers having a Fikentscher K value of from 10 to 100, and

optional pharmaceutical auxiliaries,

said mixture having a glass transition temperature below the decomposition temperature of all components of said mixture

wherein said mixture is heated, without thermal and/or oxidative degradation, at a temperature of from 50°

to 180°

to render the mixture extrudable and said heated mixture is extruded at from 50°

to 180° and

the still formable extrudate is pressed between two belts or a belt and a roller to give tablets, said two belts or said belt and a roller making contact in parts, rotating in opposite directions and running parallel along a contact zone, at least one of said two belts or at least one of said belt and a roller having shape-imparting indentations.

2. A process as claimed in claim 1, wherein two resilient belts having indentations which are opposite one another and, in pairs, determine the tablet shape are used.

3. A process as claimed in claim 1, wherein two metal link belts which contain the shape-imparting indentations in corresponding pairs are used.

4. A process as claimed in claim 1, wherein a rotating roller having shape-imparting indentations engraved on the lateral surface of the roller is used together with a smooth belt which rests against a segment of the lateral surface of the roller and revolves with the said surface.

5. A process as claimed in claim 4, wherein the revolving, smooth belt is replaced by a stationary, smooth wall.

6. A process as claimed in claim 1, wherein a rotating smooth roller is used together with a resilient belt which has the shape-imparting indentations in the contact surface.

7. A process as claimed in claim 2, wherein, instead of the second belt, a roller which rotates synchronously in contact with the first belt and on whose lateral surface engraved shape-imparting indentations correspond in pairs with those of the belt is used.

8. A process as claimed in claim 1, wherein the thermoplastic polymer used is a solvent-free N-vinylpyrrolidone polymer which has a water content of not more than 3.5% by weight and contains not less than 20% by weight of N-vinylpyrrolid-2-one (NVP) as copolymerized units, all comonomers which may be copolymerized containing nitrogen and/or oxygen.

9. A process as claimed in claim 8, wherein the thermoplastic polymer used contains not less than 60% by weight of NVP as copolymerized units.

10. A process as claimed in claim 8, wherein the thermoplastic polymer used consists of polyvinylpyrrolidone or contains only vinyl acetate as copolymerized units in addition to NVP.

11. A process as claimed in claim 8, wherein a thermoplastic polymer is used whose comonomers are selected from the following group:

acrylic acid, methacrylic acid, crotonic acid, maleic acid (anhydride), itaconic acid (anhydride), esters of the stated acids or halfesters of the stated dicarboxylic acids with alcohols of 1 to 12 carbon atoms, hydroxyethyl and hydroxypropyl acrylate and methacrylate, acrylamide, methacrylamide, N-vinylcaprolactam and vinyl propionate.

12. A process as claimed in claim 8, wherein the thermoplastic polymer used is an NVP polymer which has been prepared either in an organic solvent or using an organic peroxide in water.

13. A process as claimed in claim 8, wherein not more than 20% by weight, based on the polymer, of plasticizers are used.

14. A process as claimed in claim 1, wherein the active compound used is one which is sparingly soluble in water, forms a molecular disperse phase in the polymer melt without the addition of solvents or water and forms a solid solution after solidification of the melt.

15. A process as claimed in claim 14, wherein one or more active compounds from the following group are used:

acetaminophen (=paracetamol), acetohexamide, acetyldigoxin, acetylsalicylic acid, acromycin, anipamil, benzocaine, β

-carotene, chloramphenicol, chlordiazepoxide, chlormadinone acetate, chlorothiazide, cinnarizine, clonazepam, codeine, dexamethasone, diazepam, dircumarol, digitoxin, digoxin, dihydroergotamine, drotaverine, flunitrazepam, furosemide, gramicidin, griseofulvin, hexobarbital, hydrochlorothiazide, hydrocortisone, hydroflumethiazide, indomethacin, ketoprofen, lonetil, medazepam, mefruside, methandrostenolone, methylprednisolone, methylsulfadiazine (=sulfaperin), nalidixic acid, nifedipine, nitrazepam, nitrofurantoin, nystatin, estradiol, papaverine, phenacetin, phenobarbital, phenylbutrazone, phenytoin, prednisone, reserpine, spironolactone, streptomycin, sulfadimidine(=sulfamethazine), sulfamethizole, sulfamethoxazole, sulfamethoxydiazine (=sulfameter), sulfaperin sulfathiazole, sulfisoxazole, testosterone, tolazamide, tolbutamide, trimethoprim and tyrothricin.

16. A process as claimed in claim 1, wherein an NVP polymer having a Fikentscher K value of from 10 to 50 is used.

17. A process as claimed in claim 1, wherein an NVP polymer having a Fikentscher K value of from 12 to 35 is used.

18. A process as claimed in claim 1, wherein said mixture is heated at a temperature of from 60 to 130°

C.

19. A process as claimed in claim 1, wherein said mixture has a glass transition temperature less than 180°

C.

20. A process as claimed in claim 19, wherein said mixture has a glass transition temperature less than 130°

C.