Controlled release dosage forms
View Patent ↗The invention provides stable controlled release monolithic coating compositions for use in coating pharmaceutical oral dosage forms comprising a polyglycol having a melting point greater than 55° C. and an aqueous dispersion of a neutral ester copolymer lacking functional groups.
1. A controlled release oral dosage form comprising:
a) a core, wherein said core comprises:
i) an effective amount of metformin hydrochloride, and
ii) one or more first pharmaceutically acceptable excipients, and
b) a stable controlled release monolithic coating surrounding the core, wherein the stable controlled release coating is formed by a process comprising:
coating the core with a coating composition to form a coated core, and curing the coated core to form the stable controlled release coating, wherein the coating composition comprises
i) an aqueous dispersion of a neutral ester copolymer without any functional groups;
ii) a poly glycol having a melting point of at least about 55° C., and
iii) one or more second pharmaceutically acceptable excipients; and wherein the curing is conducted at a temperature at least equal to or greater than the melting point of the poly glycol,
wherein the stable controlled release coating hydrates when placed into water, and wherein the one or more first pharmaceutically acceptable excipients comprises cross-linked polyvinylpyrrolidone.
2. The controlled release oral dosage form of claim 1 wherein the effective amount of the metformin hydrochloride is more than about 500 mg.
3. The controlled release oral dosage form of claim 1 wherein the effective amount of the metformin hydrochloride is about 1000 mg.
4. The controlled release oral dosage form of claim 1 wherein the dosage form floats when placed in an aqueous environment.
5. The controlled release oral dosage form of claim 1 wherein the dosage form expands when placed in an aqueous environment.
6. The controlled release oral dosage form of claim 1 wherein upon oral administration to a patient, an effective amount of the metformin hydrochloride is released into a region of the patient's upper gastrointestinal tract.
7. The controlled release oral dosage form of claim 1 wherein upon oral administration to a patient, the dosage form remains substantially intact until substantially all of the active agent is released.
8. The controlled release oral dosage form of claim 1 wherein the stable controlled release monolithic coating is formed by a process that excludes usage of an organic solvent.
9. The controlled release oral dosage form of claim 1 , wherein the one or more first pharmaceutically acceptable excipients comprises at least one of colloidal silicon dioxide, polyvinyl alcohol, crospovidone, glyceryl behenate, and a mixture thereof
10. The controlled release oral dosage form of claim 1 , wherein the one or more second pharmaceutically acceptable excipients comprises at least one of hypromellose, talc, titanium dioxide, simethicone, polysorbate 80, and a mixture thereof
11. The controlled release oral dosage form of claim 1 , wherein the one or more second pharmaceutically acceptable excipients comprises at least one of an anti-tacking agent agent, an emulsifying agent agent, a hydrophilic agent, an antifoaming agent, a flavorant, a colorant, a sweetener and a mixture thereof
12. The controlled release oral dosage form of claim 1 wherein the aqueous dispersion of neutral ester copolymer without any functional groups comprises at least one of a 30% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methacrylate, a 40% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methacrylate, and mixtures thereof.
13. The controlled release oral dosage form of claim 1 wherein the poly glycol comprises at least one of polyethylene glycol 4000, polyethylene glycol 4600, polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 12000, polyethylene glycol 20000, polyethylene glycol 35000, poloxamer 188, poloxamer 338, poloxamer 407, polyethylene oxides, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and a mixture thereof.
14. The controlled release oral dosage form of claim 1 wherein the curing is conducted for a time period of from about 1 to about 24 hours.
15. The controlled release oral dosage form of claim 1 wherein the curing is conducted for a time period of from about 1 to about 16 hours.
16. The controlled release oral dosage form of claim 1 wherein the curing is conducted for a time period of from about 2 to about 7 hours.
17. The controlled release oral dosage form of claim 1 wherein the curing is conducted for a time period of from about 4 to about 7 hours.
18. The controlled release oral dosage form of claim 1 wherein the curing is conducted for a time period of from about 2 to about 4 hours.
19. The controlled release oral dosage form of claim 1 wherein the curing is conducted for a time period of from about 1 to about 3 hours.
20. The controlled release oral dosage form of claim 1 wherein the curing is conducted at a temperature at least equal to or greater than about 60 degrees C.
21. A controlled release oral dosage form comprising:
a) a core, wherein said core comprises:
i) metformin hydrochloride, and
ii) one or more first pharmaceutically acceptable excipients, and
b) a stable controlled release monolithic coating surrounding the core, wherein the stable controlled release monolithic coating is formed by a process comprising:
coating the core with a coating composition to form a coated core, and curing the coated core to form the stable controlled release coating, wherein the coating composition comprises
i) an ethyl acrylate and methyl methacrylate copolymer dispersion;
ii) a poly glycol comprising at least one of polyethylene glycol 4000, polyethylene glycol 4600, polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 12000, polyethylene glycol 20000, polyethylene glycol 35000, and a mixture thereof, and
iii) one or more second pharmaceutically acceptable excipients wherein the poly glycol has a melting point of at least about 55° C; and wherein the curing is conducted at a temperature at least equal to or greater than the melting point of the poly glycol,
wherein the stable controlled release coating hydrates when placed into water, and wherein the one or more first pharmaceutically acceptable excipients comprises cross-linked polyvinylpyrrolidone.