Process for producing solid drug forms having at least two phases

• US 6,001,391 A
• Filed: 03/10/1998
• Issued: 12/14/1999
• Est. Priority Date: 03/12/1997
• Status: Expired due to Term

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: BASF AG (BASF SE)
• Inventors: Zeidler, Jurgen, Breitenbach, Jorg, Rosenberg, Joerg, Maier, Werner, Kleinke, Andreas
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Seidleck, Brian K.
• Application Number:
  US09/037,706
• Time in Patent Office: 644 Days
• Field of Search: 424/464, 424/472, 424/467, 424/468, 424/465, 424/480, 424/482
• US Class Current: 424/467
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• 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 11/16 using pocketed rollers, e.g. two co-operating pocketed rollers
• CPC Class Codes: B30B 11/34 for coating articles, e.g. tablets
• CPC Class Codes: B30B 15/308 in a continuous manner, e.g. for roller presses, screw extrusion presses

Abstract

A process for producing solid combination tablets which have at least two phases comprises molding a melt of a polymeric binder with or without at least one active ingredient, there being at least one solid product, which may contain an active ingredient incorporated into the still plastic composition during the molding step.

Claims

1. A process for producing solid combination drug forms which have at least a first phase and a second phase, wherein at least the first phase contains a pharmacologically acceptable polymeric binder and at least one of the first and the second phase contains a pharmaceutically active ingredient, comprising

(i) providing a plastic melt of a polymeric binder (binder A) with or without at least one active ingredient, which forms the first phase,

(ii) molding the plastic melt to the drug form, and

(iii) incorporating in the plastic melt during the molding step at least one solid product which may contain at least one active ingredient which solid product forms the second phase.

2. The process of claim 1, wherein the solid product is a solidified melt of a pharmacologically acceptable polymeric binder (binder B) containing an element of the group consisting of active ingredient, a solidified active ingredient, a solidified active ingredient melt, a tablet, a pill, a pellet, active ingredient crystals and mixtures thereof.

3. The Process of claim 2, wherein binder (B) is selected from the group consisting of an alkylcellulose, hydroxyalkylcellulose, carboxyalkylcellulose, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone and vinyl acetate, a sugar alcohol and a polyethylene glycol.

4. The process of claim 1, wherein the molding of the melt takes place by extruding and shaping in a calender with molding rolls which rotate in opposite directions and have on their surface depressions to receive and shape the melt.

5. A process as claimed in claim 4, wherein the solid product is introduced into the depressions of one molding roll.

6. A process as claimed in claim 5, wherein the melt of polymeric binder (B) containing active ingredient or the active ingredient melt is introduced into the depressions of one molding roll, and the melt is caused to solidify.

7. A process as claimed in claim 4, wherein two molding rolls which have different depressions are combined.

8. A process as claimed in claim 4, wherein a molding roll with depressions is combined with a smooth roll.

9. A process as claimed in claim 4, wherein the depressions of the molding roll(s) are coated with a mold release agent.

10. A process as claimed in claim 1, wherein the combination drug forms are provided with a coating.

16. A solid combination drug form which has at least two phases and is obtained by a process as defined in claim 1.

11. A solid combination drug form which has at least two phases which comprises a first phase of at least one pharmacologically acceptable polymeric binder (binder A) in the form of a solidified melt optionally containing, at least one pharmaceutically active ingredient and into which a solid product which contains at least one active ingredient is taken up as second phase.

12. A combination drug form as defined in claim 11, wherein the solid product is a solidified melt of a pharmacologically acceptable polymeric binder (binder B) containing one or more of an element selected from the group consisting of active ingredient, a solidified active ingredient melt, a tablet, a pill, a pellet, active ingredient crystals.

13. A combination drug form as defined in claim 12, wherein the binder (B) is an alkylcellulose, hydroxyalkylcellulose, carboxyalkylcellulose, polyvinylpyrrolidone, a copolymer of N-vinylpyrrolidone and vinyl acetate, a sugar alcohol or a polyethylene glycol.

14. A combination drug form as defined in claim 11 in the form of a tablet.

15. A combination drug form as defined in claim 11, which is provided with a coating.