Polyethylene oxide-based films and drug delivery systems made therefrom
View Patent ↗The invention relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. Desirably, the films disintegrate in water and may be formed by a controlled drying process, or other process that maintains the required uniformity of the film. The films contain a polymer component, which includes polyethylene oxide optionally blended with hydrophilic cellulosic polymers. Desirably, the films also contain a pharmaceutical and/or cosmetic active agent with no more than a 10% variance of the active agent pharmaceutical and/or cosmetic active agent per unit area of the film.
1. A process for making a film having a substantially uniform distribution of components, comprising the steps of:
(a) forming a flowable polymer matrix comprising a water-soluble polymer composition comprising polyethylene oxide, at least 30% solvent and an active component, said matrix having a uniform distribution of said active component;
(b) casting said flowable polymer matrix;
(c) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said uniform distribution of said active component by locking-in or substantially preventing migration of said active component within said visco-elastic film; and
(d) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said uniform distribution of active by said locking-in or substantially preventing migration of said active component is maintained.
2. The process according to claim 1 , wherein the step of casting said matrix comprises casting onto a surface having top and bottom sides.
3. The process according to claim 2 , wherein the step of evaporating further comprises applying heat to said bottom side of said surface.
4. The process according to claim 1 , wherein said water-soluble polymer comprises at least about 20% by weight polyethylene oxide.
5. The process according to claim 1 , wherein said water-soluble polymer comprises about 20% to about 100% by weight polyethylene oxide.
6. The process according to claim 1 , further comprising a hydrophilic cellulosic polymer present in the amount of about 0% to about 80% by weight of said water-soluble polymer composition, wherein said hydrophilic cellulosic polymer is selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose and combinations thereof.
7. The process according to claim 6 , wherein said water-soluble polymer composition comprises said hydrophilic cellulosic polymer in a ratio of up to about 4:1 with polyethylene oxide.
8. The process according to claim 1 , wherein said water-soluble polymer composition comprises polyethylene oxide having a molecular weight of about 100,000 to about 900,000.
9. The process according to claim 1 , wherein said water-soluble polymer composition comprises polyethylene oxide having a molecular weight of about 100,000 to about 4 million.
10. The process according to claim 1 , wherein said water-soluble polymer composition comprises polyethylene oxide having a molecular weight of about 100,000 to about 300,000 in combination with polyethylene oxide having a molecular weight of about 600,000 to about 900,000.
11. The process according to claim 1 , wherein said water-soluble polymer composition comprises at least 1 mg polyethylene oxide.
12. The process according to claim 1 , wherein said water-soluble polymer composition comprises no greater than about 200 mg polyethylene oxide.
13. The process according to claim 1 , wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.
14. The process according to claim 1 , wherein said matrix of step (a) further comprises a densifying agent.
15. The process according to claim 14 , wherein said densifying agent is simethicone.
16. The process according to claim 1 , wherein said matrix of step (a) further comprises a solubility enhancing agent.
17. The process according to claim 1 , wherein said water-soluble polymer composition consists essentially of polyethylene oxide in the amount of about 20% to about 100% by weight of the polymer composition and a hydrophilic cellulosic polymer selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose and combinations thereof in the amount of about 0% to about 80% by weight of the polymer composition.
18. The process according to claim 1 , wherein said matrix of step (a) further comprises an anti-foaming or surface-tension reducing agent and is free of bubbles.
19. The process according to claim 1 , wherein the temperature of said matrix is 100° C. or less.
20. The process according to claim 1 , wherein said resulting film has a thickness of about 2 mils to about 10 mils.
21. The process of claim 1 , wherein said evaporating is conducted by applying radiant energy selected from the group consisting of air currents, heat, infrared radiation, radio frequency radiation and combinations thereof.
22. The process of claim 1 , wherein said visco-elastic film is further dried.
23. The process of claim 1 , wherein said visco-elastic film is a solid.
24. The process of claim 1 , wherein said visco-elastic film is formed within about 4 minutes.
25. A process for making a film having a substantially uniform distribution of components, comprising the steps of:
(a) forming a flowable polymer matrix comprising a water-soluble polymer, a solvent and an active, said matrix having a uniform distribution of said active;
(b) casting said flowable polymer matrix;
(c) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said uniform distribution of said active by locking-in or substantially preventing migration of said active within said visco-elastic film; and
(d) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained.
26. The process according to claim 25 , wherein said resulting film has a thickness of about 2 mils to about 10 mils.
27. The process of claim 25 , wherein said evaporating is conducted by applying radiant energy selected from the group consisting of air currents, heat, infrared radiation, radio frequency radiation and combinations thereof.
28. The process of claim 25 , wherein the visco-elastic film is formed within about 4 minutes.
29. The process of claim 25 , wherein the visco-elastic film is further dried.
30. The process of claim 25 , wherein the visco-elastic film is a solid.