Administration form for the oral application of poorly soluble drugs

• US 20050095293A1
• Filed: 09/03/2004
• Published: 05/05/2005
• Est. Priority Date: 03/07/2002
• Status: Abandoned Application

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Brickl, Rolf-Stefan, Brauns, Ulrich
• Application Number:
  US10/934,140
• Publication Number:
  US 20050095293A1
• Time in Patent Office: Days
• US Class Current: 424/469
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

The invention relates to a new formulation for oral administration of active substances with pH-dependent solubility characteristics and the pharmacologically acceptable salts thereof, which improves the bioavailability of the active substance.

Claims

1. Pharmaceutical composition with a bioavailability of the active substance which is substantially independent of the gastric pH, for oral administration of active substances with pH-dependent solubilities and a dose number of more than 1 at a pH>

5, comprising a plurality of pellets synthesised in each case from

a) a core material,

b) an optional insulating layer,

c) an active substance layer and

d) an optional coating,

wherein the core material consists of one or more pharmaceutically acceptable organic acid(s) with a water solubility of more than 1 g/250 ml at 20°

C., optionally with the addition of binders or other technological adjuvants.

2. Pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable organic acid is chosen from tartaric acid, fumaric acid, succinic acid, citric acid, malic acid, glutamic acid and aspartic acid or one of the hydrates or acid salts thereof.

3. Pharmaceutical composition according to claim 2, characterised in that the pharmaceutically acceptable organic acid is chosen from tartaric acid, fumaric acid, citric acid or succinic acid.

4. Pharmaceutical composition according to claim 2, characterised in that the pharmaceutically acceptable organic acid is tartaric acid.

5. Pharmaceutical composition according to claim 1, wherein the binder is selected from the group comprising the hydroxypropylcelluloses, the hydroxypropylmethylcelluloses, the methylcelluloses, the hydroxyethylcelluloses, the carboxymethylcelluloses, the polyvinylpyrrolidones, the copolymers of N-vinylpyrrolidone and vinyl acetate or combinations of these polymers.

6. Pharmaceutical composition according to claim 1 wherein the core material has an average particle size of 0.4 to 1.5 mm.

7. Pharmaceutical composition according to claim 1, wherein the insulating layer consists of a water-soluble polymer, optionally with the addition of suitable plasticisers, separating agents and pigments.

8. Pharmaceutical composition according to claim 7, wherein said water-soluble polymer consists of gum arabic or a partially or totally synthetic polymer selected from among the hydroxypropylcelluloses, the hydroxypropylmethylcelluloses, the methylcelluloses, the hydroxyethylcelluloses, the carboxymethylcelluloses, the polyvinylpyrrolidones, the copolymers of N-vinylpyrrolidone and vinyl acetate or combinations of said polymers.

9. Pharmaceutical composition according to claim 1, wherein the coating consists of film-forming agents, plasticisers and optionally pigments.

10. Pharmaceutical composition according to claim 1 wherein said pellets containing active substance are packed into hard capsules.

11. Process for preparing a pharmaceutical composition for oral administration containing an active substance with pH-dependent solubility characteristics and a dose number>

>

1 at pH>

5 or one of the physiologically acceptable salts thereof, comprising the steps of;

a) synthesising the core material from one or more pharmaceutically acceptable organic acid(s) with a water solubility of more than 1 g/250 ml at 20°

C., optionally with the addition of binders or other technological adjuvants, by pan methods, on pelleting plates or by extrusion/spheronisation,

b) applying an insulating layer consisting of one or more water-soluble, pharmaceutically acceptable polymers, optionally with the addition of plasticisers, separating agents and/or pigments, to the core material,

c) applying the active substance from a dispersion containing binder and optionally separating agent, and simultaneously or subsequently drying to eliminate the dispersing agent,

d) optionally applying a coating of film-forming agents, plasticisers and optionally pigments and

e) packing the pellets containing active substance thus obtained into hard capsules.