Delivery system for the localized administration of medicaments to the upper respiratory tract and methods for preparing and using same

• US 5,912,007 A
• Filed: 12/06/1996
• Issued: 06/15/1999
• Est. Priority Date: 02/29/1996
• Status: Expired due to Term

• Current Assignee: Intercontinental Great Brands LLC (Mondelez International, Inc.)
• Original Assignee: Warner-Lambert Company (Pfizer Inc.)
• Inventors: Pan, Pauline C., Luo, Shiuh J., Sheu, Shan Shan
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US08/761,458
• Time in Patent Office: 921 Days
• Field of Search: 514/948, 514/817, 424/439, 424/440, 424/441
• US Class Current: 424/440
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/4453 only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

The present invention pertains to delivery systems for the localized administration of a medicament to the upper respiratory tract. The delivery system comprises:

(a) a safe and effective amount of a medicament useful for treating the upper respiratory tract,

(b) an ionic polysaccharide, and,

(c) a cross-linking agent.

This invention also pertains to the medicated compositions containing the targeted delivery system in a pharmaceutically acceptable carrier. The invention further pertains to methods for preparing and using the delivery systems and medicated compositions.

Claims

1. A medicated composition for the localized administration of a medicament to the upper respiratory tract which comprises:

(a) a safe and effective amount of a medicament useful for treating the upper respiratory tract,

(b) an ionic polysaccharide,

(c) a cross-linking agent to polymerize the ionic polysaccharide wherein said cross-linking agent contains a multivalent ion selected from the group consisting of aluminum, calcium, copper, iron, magnesium, manganlese, zinc, and mixtures thereof,

said components (a) (b) and (c) being incorporated into a carrier which is a soft confectionery material or a hard confectionery material, said confectionery material prepared from a high boiling syrup, said material suitable for administration of a medicament to the upper respiratory tract,

wherein said medicament is present in an amount from about 0.001% to about 12%, by weight of the delivery system, said ionic polysaccharide is present in an amount from about 0.001% to about 1%, by weight of the composition, and, said cross-linking agent is present in an amount from about 0.001% to about 1.2%, by weight of the composition,

such that said polymerization of said ionic polysaccharide takes place in said upper respiratory tract upon the dissolution of said carrier.

2. The medicated composition according to claim 1, wherein the medicament useful for treating the upper respiratory tract is selected from the group consisting of analgesics, topical anesthetics, antitussives, topical antimicrobials, antihistamines, decongestants, expectorants, cell and tissue healing agents, bronchodilators, steroidal anti-inflammatory agents, and mixtures thereof.

3. The medicated composition according to claim 2 wherein the medicament is an analgesic, topical anesthetic or antitussive.

4. The medicated composition according to claim 3 wherein the medicament is an antitussive.

5. The medicated composition according to claim 4 wherein the medicament is menthol.

6. The medicated composition according to claim 3, wherein the medicament is a topical anesthetic agent.

7. The medicated composition according to claim 6, wherein the medicament is dyclonine hydrochloride.

8. The medicated composition according to claim 1, wherein the ionic polysaccharide selected from the group consisting of algin, carrageenan and pectin.

9. The medicated composition according to claim 8 wherein the ionic polysaccharide is a monocationic salt.

10. The medicated composition according to claim 9 wherein the salt is sodium.

11. The medicated composition according to claim 1, wherein the cross-linking agent is selected from the group consisting of calcium stearate, calcium lactate, calcium tartrate, calcium sulfate, monocalcium phosphate, tricalcium phosphate, dicalcium phosphate dihydrate and mixtures thereof.

12. The medicated composition according to claim 11, wherein the cross-linking agent is calcium lactate.

13. The medicated composition according to claim 1, wherein the cross-linking agent is premixed with a sequestering agent.

14. The medicated composition according to claim 13, wherein the sequestering agent is selected from the group consisting of sodium citrate, tetrasodium phosphate, sodium hexametaphosphate, ethylene diamine tetraacetic acid.

15. The medicated composition according to claim 1, wherein the delivery system further comprises a pharmaceutically acceptable acid selected from the group consisting of citric acid, fumaric acid, malic acid, tartaric acid, lactic acid, adipic acid, phosphoric acid, benzoic acid, glutamic acid, sorbic acid, propionic acid, erythorbic acid, tannic acid, succinic acid, aconitic acid, ascorbic acid, and mixtures thereof.

16. The medicated composition according to claim 15, wherein the pharmaceutically acceptable acid is selected from the group consisting of citric acid, fumaric acid, malic acid, tartaric acid, lactic acid, adipic acid, phosphoric acid, and mixtures thereof.

17. The medicated composition according to claim 16 wherein the pharmaceutically acceptable acid is citric acid.

18. The medicated composition according to claim 1, wherein the pharmaceutically acceptable acid is present in an amount from about 0.001% to about 1.2%, by weight of the delivery system.

19. The medicated composition according to claim 1, wherein the medicament is premixed with a pharmaceutically acceptable oil and an emulsifier having a hydrophilic-lipophilic balance in the range from about 1 to about 10.

20. The medicated composition according to claim 19, wherein the pharmaceutically acceptable oil is selected from the group consisting of animal, vegetable, marine, and synthetic oils, fats, and waxes.

21. The medicated composition according to claim 19, wherein the emulsifier having a hydrophilic-lipophilic balance in the range from about 1 to about 10 is selected from the group consisting of decaglycerol decaoleate, lecithin and sorbitan fatty acid esters.

22. The medicated composition according to claim 19, wherein the pharmaceutically acceptable oil is vegetable oil and the emulsifier is decaglycerol decaoleate.

25. The medicated composition according to claim 1 wherein the confectionery material is in the form of a lozenge, toffee, nougat or chewy candy.

23. A method for preparing a medicated composition useful for the localized administration of medicaments to the upper respiratory tract which comprises the steps of:

(1) providing the following ingredients;

(a) a safe and effective amount of a medicament useful for treating the upper respiratory tract,

(b) an ionic polysaccharide,

(c) a cross-linking agent to polymerize the ionic polysaccharide wherein said cross-lining agent contains a multivalent ion selected from the group consisting of aluminum, calcium, copper, iron, magnesium, manganese, zinc, and mixtures thereof, and,

(d) a carrier which is a soft confectionery material or a hard confectionery material, said confectionery material prepared from a high boiling syrup, said material suitable for administration of a medicament to the upper respiratory tract,

wherein said medicament is provided in an amount from about 0.001% to about 12%, by weight of the delivery system, said ionic polysaccharide is provided in an amount from about 0.001% to about 1%, by weight of the composition, and, said cross-linking agent is provided in an amount from about 0.001% to about 1.2%, by weight of the composition, such that said polymerization of said ionic polysaccharide takes place in said upper respiratory tract upon the dissolution of said carrier, and,

(2) admixing the ingredients from step (1) to form the medicated composition.

26. The method according to claim 23 wherein the confectionery material is in the form of a lozenge, toffee, nougat or chewy candy.

24. A method for the local administration of a medicament to the upper respiratory tract of a patient which comprises orally administering a medicated composition which comprises:

(a) a safe and effective amount of a medicament useful for treating the upper respiratory tract,

(b) an ionic polysaccharide,

(c) a cross-linking agent to polymerize the ionic polysaccharide wherein said cross-linking agent contains a multivalent ion selected from the group consisting of aluminum, calcium, copper, iron, magnesium, manganese, zinc, and mixtures thereof,

said components (a) (b) and (c) being incorporated into a carrier which is a soft confectionery material or a hard confectionery material, said confectionery material prepared from a high boiling syrup, said material suitable for administration of a medicament to the upper respiratory tract,

wherein said medicament is present in an amount from about 0.001% to about 12%, by weight of the delivery system, said ionic polysaccharide is present in an amount from about 0.001% to about 1%, by weight of the composition, said, the cross-linking agent is present in an amount from about 0.001% to about 1.2%, by weight of the composition, such that said polymerization of said ionic polysaccharide takes place in said upper respiratory tract upon the dissolution of said carrier.

27. The method according to claim 24 wherein the confectionery material is in the form of a lozenge, toffee, nougat or chewy candy.