Controlled-release PH sensitive capsule and adhesive system and method

• US 5,364,634 A
• Filed: 11/08/1991
• Issued: 11/15/1994
• Est. Priority Date: 11/08/1991
• Status: Expired due to Fees

• Current Assignee: Southwest Research Institute
• Original Assignee: Southwest Research Institute
• Inventors: Lew, Chel W.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US07/790,639
• Time in Patent Office: 1,103 Days
• Field of Search: 424/435, 424/451, 424/496, 424/434, 424/471
• US Class Current: 424/451
• CPC Class Codes: A61K 2800/412 Microsized, i.e. having sizes between 0.1 and 100 microns
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61Q 11/00 Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Abstract

A capsule and method for delivery for an active ingredient in the oral cavity that has a pH sensitive encapsulant shell and is associated with an adhesive. The pH sensitive shell dissolves at a pH in the oral cavity while the adhesive allows dissolution at the selected tissue.

Claims

1. A capsule for adhesion in the oral cavity comprising

at least one internal active ingredient;

a non-toxic pH sensitive shell encapsulating said active ingredient and said shell is insoluble in a preselected pH of less than 6;

said shell dissolving at the pH 6.4 and above which is present in the oral cavity; and

a non-toxic adhesive system associated with the outer surface of said shell which permits adhesion of the capsule to selected tissue inside the oral cavity for a period of time to allow for the dissolution of said shell and release of the active ingredient.

2. A capsule for adhesion in the oral cavity of claim 1 additionally comprising a water dispersible lipid coating surrounding the active ingredient which is encapsulated with the pH sensitive shell.

3. A capsule for adhesion in the oral cavity of claim 1 wherein said active ingredient is selected from the group consisting of drugs, enzymes, breath fresheners, flavors, preservatives, or mixture thereof.

4. A capsule for adhesion in the oral cavity of claim 1 wherein said pH sensitive shell is selected from the group of pH sensitive acrylic resins, plasticized hydrocarbon gel, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, and mixtures thereof.

5. A capsule for adhesion in the oral cavity of claim 1 wherein said adhesive system is selected from the group of calcium polycarbophil, polyacrylic acid, gelatin, carboxymethyl cellulose, natural gums, algin, chitosan, hydroxypropylmethyl cellulose, starches, pectins or mixtures thereof which are applied to the outside of the shell of the capsules.

6. A capsule of claim 1 wherein the non-toxic pH sensitive shell and the adhesive are combined to form a pH sensitive bioadhesive encapsulant.

7. A formulation for adhesion in the oral cavity comprising

a plurality of capsules made of at least one internal active ingredient with a non-toxic shell encapsulating said active ingredient which is insoluble at a preselected pH of less than 6 and said non-toxic shell dissolving at the pH 6.4 and above which is present in the oral cavity;

and

said capsules contained in a non-toxic adhesive system such that the mixture of the capsules and the adhesive allows for the adhesion of the mixture to a selected site inside the oral cavity for a sustained period of time to allow for the dissolution of the shell and the release of the active ingredient.

8. A formulation for adhesion in the oral cavity of claim 7 wherein said non-toxic adhesive system comprises an aqueous gel with a pH at a preselected level to maintain the integrity of the pH sensitive shell of the capsules.

9. A method of delivering an active ingredient to the oral cavity comprising the steps of

encapsulating at least "one" active ingredient with a non-toxic shell which is insoluble at a preselected pH of less than 6 to form microcapsules;

associating a plurality of microcapsules with an adhesive system which does not affect the stability of the shell;

maintaining the stability of the microcapsules by keeping the microcapsules at a pH at which the shell is insoluble and stable; and

introducing the microcapsules with the adhesive system associated therewith into the oral cavity, the adhesive system causing the microcapsules to adhere to a selected site in the oral cavity for a period of time, the pH 6.4 and above which is present in the oral cavity destabilizing the shell of the microcapsules thereby releasing the active ingredient at the selected site in the oral cavity.

10. A method of claim 9 additionally comprising the step of encapsulating the active ingredient with an inner lipid coating which is dispersible inside the oral cavity before encapsulating with the pH sensitive material.

11. A method of claim 9 wherein said encapsulant and said adhesive are combined to form a pH sensitive bioadhesive encapsulant.

12. A method of claim 9 wherein the adhesive forms a matrix containing the capsules.

13. A method of claim 9 wherein said active ingredient is selected from the group consisting of drugs, enzymes, breath fresheners, flavors, preservatives, or mixture thereof.

14. A method of claim 9 wherein said pH sensitive shell is selected from the group of pH sensitive acrylic resins, plasticized hydrocarbon gel, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, and mixtures thereof.

15. A method of claim 9 wherein said adhesive system is selected from the group of calcium polycarbophil, polyacrylic acid, gelatin, carboxymethyl cellulose, natural gums, algin, chitosan, hydroxypropylmethyl cellulose, starches, pectins and mixtures thereof which are applied to the outside of the shell of the capsules.

16. A delivery system for adhesion to the oral cavity comprising

a plurality of microcapsules with at least one active ingredient surrounded by an outer shell that is stable at preselected pH of less than 6 and dissolves in the oral cavity at a pH of 6.4 and above which is present in the oral cavity;

an adhesive associated with the outer shell of the microcapsule which does not affect the integrity of the outer shell; and

said adhesive causing adhesion of the microcapsules in the oral cavity for a period of time to allow dissolution of the shell and release of the active ingredient.

17. A delivery system for the oral cavity of claim 16 additionally comprising a water dispersible inner lipid layer surrounding the active ingredient between the outer shell and said active ingredient.

18. A delivery system of claim 16 wherein the adhesive forms a matrix containing the microcapsules.

19. A delivery system of claim 16 wherein the adhesive is an aqueous gel with the pH adjusted to the preselected level to maintain the integrity of the outer shell of the microcapsules.

20. A delivery system of claim 16 wherein the microcapsules are a mixture of microcapsules encapsulating selected active ingredients.

21. A delivery system of claim 16 wherein said outer shell and adhesive are combined to form a pH sensitive bioadhesive encapsulant.

22. A delivery system of claim 16 wherein said adhesive is selected from the group of calcium polycarbophil, polyacrylic acid, gelatin, carboxymethyl cellulose, natural gums, algin, chitosan, hydroxypropylmethyl cellulose, starches, pectins and mixtures thereof.

23. A delivery system of claim 16 wherein said pH sensitive shell is selected from the group of pH sensitive acrylic resins, plasticized hydrocarbon gel, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate phthalate, and cellulose acetate trimellitate.

24. A delivery system of claim 16 wherein said active ingredients are selected from the group of drugs, enzymes, breath fresheners, flavors, preservatives, and mixtures thereof.