Oral pharmaceutical composition for acid sensitive proteinaceous agents

• US 5,032,405 A
• Filed: 09/27/1989
• Issued: 07/16/1991
• Est. Priority Date: 09/27/1989
• Status: Expired due to Fees

• Current Assignee: Warner-Lambert Company (Pfizer Inc.)
• Original Assignee: Warner-Lambert Company (Pfizer Inc.)
• Inventors: Huang, Hua-pin, Fawzi, Mahdi B., Ghebre-Sellassie, Isaac
• Primary Examiner(s): Page, Thurman
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US07/413,197
• Time in Patent Office: 657 Days
• Field of Search: 424/463, 424/89, 424/465, 424/482
• US Class Current: 424/463
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004

Abstract

An orally administrable formulation of a biologically active, acid sensitive, proteinaceous agent comprises a composition of a lyophilized mixture of the proteinaceous agent and maltose, optionally with a particulate diluent. This composition is then uniformly coated with an alkaline-soluble polymeric film containing at least one partially esterified polymethacrylic acid as a major component.

Claims

1. An orally administrable formulation of a biologically active, hormone, antibiotic, or immunological agent which comprises (a) a composition of a lyophilized mixture comprising (i) the hormone, antibiotic, or immunological agent, (ii) maltose and (iii) a particulate diluent, said composition being uniformly coated with (b) an alkaline-soluble polymeric film comprising at least one partially esterified polymethacrylic acid as a major component.

2. An or administrable formulation according to claim 1 wherein said particulate diluent is a cellulose, mannitol, lactose, magnesium carbonate, magnesium oxide, calcium carbonate, calcium sulfate, dibasic calcium phosphate, bentonite, silica gel, talc, or starch.

3. An orally administrable formulation according to claim 2 wherein said particulate diluent is a cellulose.

4. An orally administrable formulation according to claim 3 wherein said particulate diluent is microcrystalline cellulose.

5. An orally administrable formulation according to claim 1 wherein said alkaline-soluble polymeric film comprises at least one partially methylated polymethacrylic acid having a mean molecular weight of from 130,000 to 140,000 with a ratio of esterified carboxy groups to unesterified carboxy groups of from about 2:

1 to about 1;

1.

6. An orally administrable formulation according to claim 1 wherein said film comprises a first partially methylated polymethacrylic acid soluble in an aqueous media at a pH above about 7 and having a mean molecular weight of about 135,000 with a ratio of esterified carboxy groups to unesterified carboxy groups of about 2:

1.

7. An orally administrable formulation according to claim 6 wherein said film comprises said first partially methylated polymethacrylic acid in combination with a second partially methylated polymethacrylic acid soluble in an aqueous media at a pH above about 6 and having a mean molecular weight of about 135,000 with a ratio of esterified carboxy groups to unesterified carboxy groups of about 1:

1.

8. An orally administrable formulation according to claim 1 wherein said acid sensitive proteinaceous agent is a vaccine.

9. An orally administrable formulation according to claim 8 wherein said acid sensitive proteinaceous agent is an influenza vaccine.

10. An orally administrable formulation of an influenza vaccine which comprises a capsule containing (a) a composition of a lyophilized mixture of (i) the influenza vaccine, (ii) maltose, and (iii) microcrystalline cellulose, said capsule being uniformly coated with (b) a film comprising as a major component a partially methylated polymethacrylic acid soluble in an aqueous media at a pH above about 7 and having a mean molecular weight of about 135,000 with a ratio of esterified carboxy groups to unesterified carboxy groups of about 2:

1.

11. An orally administrable formulation according to claim 10 wherein said film comprises said partially methylated polymethacrylic acid in combination with a second partially methylated polymethacrylic acid soluble in an aqueous media at a pH above about 6 and having a mean molecular weight of about 135,000 with a ratio of esterified carboxy groups to unesterified carboxy groups of about 1:

1.