Rapidly releasing and taste-masking pharmaceutical dosage form

• US 6,221,402 B1
• Filed: 09/20/1999
• Issued: 04/24/2001
• Est. Priority Date: 11/20/1997
• Status: Expired due to Fees

• Current Assignee: Pfizer Pharmaceuticals LLC (Pfizer Inc.)
• Original Assignee: Pfizer Inc.
• Inventors: Niwa, Toshiyuki, Itoh, Akinori
• Primary Examiner(s): Spear, James M.
• Application Number:
  US09/341,312
• Time in Patent Office: 582 Days
• Field of Search: 424/489, 424/464, 424/465, 424/451, 424/452, 424/455, 424/458, 424/459, 424/461, 424/462, 424/493, 424/494, 424/497, 424/490, 424/495
• US Class Current: 424/494
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings

Abstract

A rapidly-releasing and taste-masking pharmaceutical dosage form and a process for preparing such oral dosage form are disclosed.

Claims

1. A rapidly releasing and taste-masking pharmaceutical dosage form comprising a core containing a pharmaceutically active ingredient, low-substituted hydroxypropyl cellulose containing not less than 5.0% and not more than 16.0% hydroxypropoxy groups on a dried basis, and microcrystalline cellulose, the amount of the microcrystalline cellulose being at least 26.0 weight percent based on the total weight of the core;

an inner coating layer formed on the core and containing a water-soluble polymer; and

an outer coating layer formed on the inner coating layer and containing a saliva-insoluble polymer, wherein the core, the inner coating layer and the outer coating layer are contained in an amount of from 60.0 to 87.0, from 4.0 to 31.0 and from 9.0 to 36.0 weight percent, respectively, based on the total weight of the dosage form.

2. A dosage form according to claim 1, which is further coated by a sugar coating layer formed on the outer coating layer in an amount of 15.0 to 270.0 weight percent based on the total weight of a coated particle composed of the core, the inner and outer coating layers.

3. A dosage form according to claim 1, wherein the core is in a spherical form and has an average particle diameter of 80 to 400 micrometers.

4. A dosage form according to claim 1, wherein the core comprises 0.1 to 73.5 weight percent of the active ingredient, 26.0 to 99.4 weight percent of the microcrystalline cellulose and 0.5 to 34.0 weight percent of the low-substituted hydroxypropyl cellulose, the weight percent being based on the total weight of the core material.

5. A dosage form according to claim 1, wherein the core comprises 20.0 to 40.0 weight percent of the active ingredient, 30.0 to 60.0 weight percent of the microcrystalline cellulose and 3.0 to 30.0 weight percent of the low-substituted hydroxypropyl cellulose, the weight percent being based on the total weight of the core material.

6. A dosage form according to claim 1, wherein the inner coating layer comprises 70.0 to 100 weight percent of a water-soluble polymer selected from hydroxypropylmethyl cellulose and hydroxypropyl cellulose;

and up to 30.0 weight percent of a water-insoluble polymer selected from an ethylcellulose, a methacrylate copolymer and an aminoalkyl methacrylate copolymer, the weight percent being based on the total weight of the inner coating layer.

7. A dosage form according to claim 1, wherein the outer coating layer comprises 70.0 to 100 weight percent of a saliva-insoluble polymer selected form polyvinylacetal diethylaminoacetate and butyl methacrylate/(2-dimethylaminoethyl)methacrylate/methyl methacrylate copolymer;

and up to 30 weight percent of a water soluble or water-insoluble polymer selected from hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethylcellulose, an ethyl acrylate/methyl methacrylate/trimethylammonioethyl methacrylate copolymer, the weight percent being based on the total weight of the outer coating layer.

8. A process for preparing a dosage form of claim 1, which comprises mixing core materials containing a pharmaceutically active ingredient, low-substituted hydroxypropyl cellulose and microcrystalline cellulose, and subjecting the mixed core materials to wet agitation granulation, dry treatment and sieving treatment in this order to obtain core particles;

forming an inner coating layer on the core particles by spraying with an aqueous solution containing a water-soluble polymer; and

then forming an outer coating layer on the inner coating layer by spraying with an aqueous solution containing a saliva-insoluble polymer.

9. A process according to claim 8, which is carried out in the absence of a solvent harmful to a human body.