Moistureless oral drug delivery formulation and method for preparing same

• US 4,867,970 A
• Filed: 05/21/1987
• Issued: 09/19/1989
• Est. Priority Date: 05/21/1987
• Status: Expired due to Term

• Current Assignee: ER Squibb & Sons LLC (Bristol-Myers Squibb Company)
• Original Assignee: E R Squibb & Sons Incorporated
• Inventors: Rowley, Duncan J., Newsham, E. A., Forrester, Jeffrey W.
• Primary Examiner(s): Schofer, Joseph L.
• Assistant Examiner(s): Kulkosky, Peter F.
• Application Number:
  US07/052,297
• Time in Patent Office: 852 Days
• Field of Search: 424/81, 424/435
• US Class Current: 514/31
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Abstract

Oral drug delivery systems are provided formed of compositions which include one or more hydrocolloids solids, such as gelatin, pectin, and sodium carboxymethyl cellulose, and preferably mixtures thereof, which solids contain less than about 5% by weight moisture and preferably comprise less than about 50% by weight of the total formulation; and an ointment base such as mineral oil containing dispersed polyethylene (Plastibase). Such oral drug delivery compositions may be used to deliver to the oral mucosa active ingredients such as steroids, anti-fungal agents, anti-bacterial agents and the like and do not harden even upon prolonged storage or upon filling into containers.

Claims

1. An oral drug delivery system, in the form of an oral ointment formulation, comprising one or more hydrocolloids solids in an amount within the range of from about 0.5 to about 60% by weight of the formulation, containing less than about 5% by weight moisture, and an ointment base therefor, said formulation having resistance to hardening even upon prolonged storage or filling into containers, whereupon application of said formulation at the desired site of action in the oral cavity, moisture in said oral cavity causes said hydrocolloid to swell and medicament to be released and to adhere to and be retained at the desired site of action.

2. The formulation as defined in Claim 1 further including a medicament in an amount within the range of from about 0.01 to about 25% by weight of the total formulation.

3. The formulation as defined in claim 2 wherein the medicament is an antifungal agent.

4. The formulation as defined in claim 3 wherein the antifungal agent is nystatin, clotrimazole, amphotericin B, miconazole, ketoconazole or griseofulvin.

5. The formulation as defined in claim 2 wherein the medicament is a steroid.

6. The formulation as defined in claim 5 wherein said steroid is triamcinolone acetonide.

7. The formulation as defined in claim 1 wherein said hydrocolloid is gelatin, pectin, cellulose ether, a cellulose alkyl hydroxylate, a cellulose alkyl carboxylate, an alkali metal salt of a cellulose alkyl carboxylate, an acrylic acid homo- or copolymer or salt thereof, sodium alginate, carrageenan or mixtures thereof.

8. The formulation as defined in claim 1 wherein said hydrocolloid is a mixture of gelatin, pectin and sodium carboxymethyl cellulose.

9. The formulation as defined in claim 2 wherein said ointment base is mineral oil containing a thickening agent.

10. The formulation as defined in claim 9 wherein said ointment base is mineral oil containing polyethylene.

11. The formulation as defined claim 2 including one or more antifungal agent and/or antibacterial agents as the medicament.

12. The formulation as defined in claim 1 wherein the hydrocolloids solids contain less than 1% by weight moisture.

13. The formulation as defined in claim 1 wherein the hydrocolloids solids are present in an amount within the range of from about 30 to about 50% by weight of the total formulation.

14. The formulation as defined in claim 13 wherein the hydrocolloid is comprised of from about 0.5 to about 60% by weight gelatin, from about 0.5 to about 60% by weight pectin, and from about 0.5 to about 60% by weight sodium carboxymethyl cellulose, said % being based on the weight of the hydrocolloid mixture.

15. The formulation as defined in claim 10 wherein the medicament is triamcinolone acetonide, the ointment base is mineral oil thickened with polyethylene and said hydrocolloids solids is a mixture of gelatin, pectin and sodium carboxymethyl cellulose, said solids containing less than about 1% by weight moisture and being present in a weight ratio to said ointment base of within the range of from about 0.43:

1 to about 1;

1.

16. The formulation as defined in claim 1 wherein said hydrocolloids have an average particle size of less than about 100 micrometers.

17. A method for preparing an oral drug delivery system in the form of an oral ointment formulation having improved resistance to hardening during storage, as defined in claim 1, which comprises drying the hydrocolloids solids to a moisture content of less than about 5% by weight of said hydrocolloids solids, and mixing the so-dried hydrocolloids solids with said ointment base to form said oral ointment formulation.

18. The method as defined in claim 17 wherein said hydrocolloids solids are dried to about 0% moisture content.

19. The method as defined in claim 17 wherein said hydrocolloids solids are comprised of sodium carboxymethyl cellulose, pectin and gelatin and said ointment base is mineral oil containing polyethylene.