Polymer blends that swell in an acidic environment and deswell in a basic environment
View Patent ↗A polymer blend is prepared by dissolving chitosan and a second polymer in an acidic aqueous solution to form an aqueous polymer blend, dehydrating said aqueous polymer blend, and recovering said polymer blend. The second polymer may be selected from the group consisting of polyether glycols including polyethylene glycols; cellulose esters including cellulose acetate; poloxamers; polysaccharides including dextran and guar; polyvinylpyrrolidones; polyvinyl alcohols; and mixtures or copolymers thereof. These polymer blends swell in an acidic environment and deswell in a more neutral or basic environment. This technology is valuable for the dispensing of biologically active material or drugs into a surrounding environment, especially the environment as is found in the gastrointestinal tract. Since the various polymer blends of the present invention are not covalently or ionically crosslinked, but are physically combined, each polymer in the physical blend maintains its original chemical structure, and therefore, is safe for oral administration.
1. A method of delivering a drug into a neutral or basic environment within a warm-blooded animal comprising:
(a) providing a drug containing polymer blend that, when exposed to aqueous conditions, swells in an acidic environment and deswells in a neutral or basic environment, said polymer blend comprising:
(i) an effective amount of chitosan
(ii) an effective amount of a second polymer wherein said second polymer is selected from the group consisting of polyether glycols, cellulose esters, poloxamers, polysaccharides, poly vinylpyrrolidones, polyvinyl alcohols, and mixtures or copolymers thereof, said chitosan and said second polymer are not covalently or ionically crosslinked; and
(iii) a drug,
wherein said polymer blend is prepared by dissolving chitosan and a second polymer in an acidic aqueous solution to form an aqueous polymer blend, dehydrating said aqueous polymer blend, and recovering said polymer blend, wherein said drug is loaded simultaneous with or after said preparation of said polymer blend, and
wherein said acidic aqueous solution is comprised of water and an acidifying agent selected from the group consisting of acetic acid, citric acid, hydrochloric acid, and combinations thereof, and wherein said acidic aqueous solution has a concentration from about 0.5 M to 11 M; and
(b) orally administering said drug containing polymer blend to a warm-blooded animal wherein said polymer blend hydrates and swells in an acidic environment of the body and deswells in a more neutral to basic environment of the body thereby releasing said drug into the surrounding environment where in the acidic environment of the body is stomach and the neutral or basic environment of the body intestines.
2. A method as in claim 1 wherein said chitosan to said second polymer weight ratio is from about 1:4 to 10:1.
3. A method as in claim 2 wherein said second polymer is selected from the group consisting of polyether glycols, cellulose esters, poloxamers, polysaccharides, polyvinylpyrrolidones; polyvinyl alcohols, and mixtures or copolymers thereof.
4. A method as in claim 3 wherein said chitosan has a Brookfield viscosity from about 100 cps to 10,000 cps.
5. A method as in claim 1 wherein said drug containing polymer blend is prepared by dissolving said drug simultaneously with said chitosan and said second polymer in an acidic aqueous solution to form a drug containing aqueous polymer blend, and dehydrating said drug containing aqueous polymer blend to form a particulate drug containing polymer blend.
6. A method as in claim 1 wherein said drug containing polymer blend is prepared by swelling said polymer blend in an acidic solution containing said drug, equilibrating said swollen polymer blend and said drug, and dehydrating said swollen polymer blend containing said drug.
7. A method as in claim 4 wherein said drug containing polymer blend is prepared by admixing said drug in a particulate form with said polymer blend.
8. A method as in claim 1 wherein said drug containing polymer blend is delivered orally within a capsule.
9. A method as in claim 1 wherein pH controlling additives or excipients are admixed with said polymer blend to alter the swelling and deswelling properties of said polymer blend.
10. A method as in claim 9 wherein said additive or excipient is an acid selected from the group consisting of citric acid, tartaric acid, malic acid, maleic acid, and combinations thereof, and wherein said additive prolongs or accelerates the swelling of said polymer blend.
11. A method as in claim 9 wherein said additive or excipient is a base selected from the group consisting of sodium carbonate, magnesium hydroxide, disodium phosphate, and combinations thereof, and wherein said additive retards the swelling or accelerates the deswelling of said polymer blend.
12. A method as in claim 1 wherein the acidic environment of the body is the stomach and the more neutral to basic environment of the body is the intestines.
13. A method of delivering a drug into a neutral or basic environment within a warm-blooded animal comprising;
(a) providing a drug containing polymer blend that, when exposed to aqueous conditions, swells in an acidic environment and deswells in a neutral or basic environment, said polymer blend comprising:
(i) an effective amount of chitosan
(ii) an effective amount of a second polymer, said second polymer is selected from the group consisting of polyether glycols, cellulose esters, poloxamers, polysaccharides, polyvinylpyrrolidones, polyvinyl alcohols, and mixtures or copolymers thereof, said chitosan and said second polymer are not covalently or ionically crosslinked; and
(iii) a drug,
wherein said polymer blend is prepared by dissolving chitosan and a second polymer in an acidic aqueous solution to form an aqueous polymer blend, dehydrating said aqueous polymer blend, and recovering said polymer blend, wherein said drug is loaded simultaneous with or after said preparation of said polymer blend; and
(b) orally administering said drug containing polymer blend to a warm-blooded animal wherein said polymer blend hydrates and swells in an acidic environment of the body and deswells in a more neutral to basic environment of the body thereby releasing said drug into the surrounding environment, wherein the acidic environment of the body is the stomach and the more neutral to basic environment of the body is the intestines.
14. A method as in claim 13 wherein said chitosan to said second polymer weight ratio is from about 1:4 to 10:1.
15. A method as in claim 13 wherein said chitosan has a Brookfield viscosity from about 100 cps to 10,000 cps.
16. A method as in claim 13 wherein said drug containing polymer blend is prepared by dissolving said drug simultaneously with said chitosan and said second polymer in an acidic aqueous solution to form a drug containing aqueous polymer blend, and dehydrating said drug containing aqueous polymer blend to form a particulate drug containing polymer blend.
17. A method as in claim 13 wherein said drug containing polymer blend is prepared by swelling said polymer blend in an acidic solution containing said drug, equilibrating said swollen polymer blend and said drug, and dehydrating said swollen polymer blend containing said drug.
18. A method as in claim 15 wherein said drug containing polymer blend is prepared by admixing said drug in a particulate form with said polymer blend.
19. A method as in claim 13 wherein said drug containing polymer is delivered orally within a capsule.
20. A method as in claim 13 wherein pH controlling additives or excipients are admixed with said polymer blend to alter the swelling and deswelling properties of said polymer blend.
21. A method as in claim 20 wherein said additive or excipient is an acid selected from the group consisting of citric acid, tartaric acid, malic acid, maleic acid, and combinations thereof, and wherein said additive prolongs or accelerates the swelling of said polymer blend.
22. A method as in claim 20 wherein said additive or excipient is a base selected from the group consisting of sodium carbonate, magnesium hydroxide, disodium phosphate, and combinations thereof, and wherein said additive retards the swelling or accelerates the deswelling of said polymer blend.