Dissolvable gel-forming film for delivery of active agents
Disclosed is a dissolvable, gel-forming film, and methods for its use, comprising a water-soluble cellulose ether, a hydrophilic rheological modifying agent, and an active proteolytic enzyme or other drug substance. The gel-forming film has a water content of less than 15% w/w and is capable of forming a hydrogel when contacted with water or other aqueous medium. The disclosed films achieve delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes.
1. A dissolvable, gel-forming film comprising:
(a) a water-soluble cellulose ether;
(b) a hydrophilic rheological modifying agent; and
(c) a thermolysin or collagenase proteolytic enzyme,
wherein the dissolvable, gel-forming film has a water content of less than 15% w/w, and the dissolvable, gel-forming film is capable of forming a hydrogel having a viscosity of 1,000 to 100,000 cps, as measured using a Brookfield RV Model Viscometer using small sample adapter with spindle #SC4-14 and chamber #SC4-6R, at 10 rpm at room temperature, reading taken at 1 minute, when 1 gm of gel-forming film is contacted with 20 ml of water or other aqueous medium.
2. The dissolvable, gel-forming film of claim 1 , wherein the proteolytic enzyme is in crystalline form.
3. The dissolvable, gel-forming film of claim 1 , wherein the proteolytic enzyme is thermolysin.
4. The dissolvable, gel-forming film of claim 1 , wherein the thickness of the film ranges from 10 to 1000 μm.
5. The dissolvable, gel-forming film of claim 1 , wherein the film is capable of dissolving in water at a rate from 100 to 0.1 mg/min.
6. The dissolvable, gel-forming film of claim 5 , wherein the film is capable of dissolving in water at a rate from 0.5-10 mg/min.
7. The dissolvable, gel-forming film of claim 1 , wherein the weight percent of the proteolytic enzyme is not less than 0.1% of the dry weight of the film and does not decrease by more than 10% when stored at room temperature for 24 months.
8. The dissolvable, gel-forming film of claim 1 , wherein the water-soluble cellulose ether is a hydroxyalkyl cellulose ether.
9. The dissolvable, gel-forming film of claim 8 , wherein the hydroxyalkyl cellulose ether is hydroxyethylcellulose, hydroxypropylcellulose, or hydroxypropylmethylcellulose, or any combination thereof.
10. The dissolvable, gel-forming film of claim 1 , comprising 50 to 70% w/w or 55 to 65% w/w of the water-soluble cellulose ether.
11. The dissolvable, gel-forming film of claim 9 , comprising 25 to 35% w/w of hydroxyethylcellulose and 25 to 35% w/w of hydroxypropylmethyl cellulose.
12. The dissolvable, gel-forming film of claim 1 , comprising 15 to 25% w/w of the hydrophilic rheological modifying agent.
13. The dissolvable, gel-forming film of claim 12 , wherein the hydrophilic rheological modifying agent is a polyol.
14. The dissolvable, gel-forming film of claim 13 , wherein the polyol is polyethylene glycol.
15. The dissolvable, gel-forming film of claim 14 , wherein the polyethylene glycol is PEG-400.
16. The dissolvable, gel-forming film of claim 1 , comprising 5 to 15% w/w of the proteolytic enzyme.
17. The dissolvable, gel-forming film of claim 1 , wherein the hydrogel further comprises a metal salt.
18. The dissolvable, gel-forming film of claim 17 , wherein the metal salt is sodium chloride or calcium chloride or mixtures thereof.
19. The dissolvable, gel-forming film of claim 1 , wherein the hydrogel further comprises a preservative.
20. The dissolvable, gel-forming film of claim 19 , wherein the preservative is methylparaben, propylparaben, or phenoxyethanol, or mixtures thereof.
21. A method of debriding a wound comprising topically applying the dissolvable, gel-forming film of claim 1 to a wound in need of debridement.
22. The method of claim 21 , wherein the wound is a chronic wound.
23. The method of claim 22 , wherein the chronic wound is a diabetic foot ulcer, a venous leg ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, a dermal ulcer, a burn, or a pressure ulcer.
24. The method of claim 21 , wherein the wound includes necrotic tissue.
25. The method of claim 24 , wherein the necrotic tissue is an eschar.
26. The method of claim 21 , wherein an aqueous medium is applied to the wound before the dissolvable, gel-forming film is applied to the wound or wherein an aqueous medium is applied to the dissolvable, gel-forming film after said film is applied to the wound.
27. The method of claim 26 , wherein the aqueous medium is a saline solution.
28. The method of claim 21 , wherein a bandage, wound dressing, or gauze is applied onto the dissolvable, gel-forming film after said film is applied to the wound.
29. A dissolvable, gel-forming film comprising:
(a) 25 to 35% w/w of hydroxyethylcellulose and 25 to 35% w/w of hydroxypropylmethyl cellulose;
(b) 15 to 25% w/w of a polyethylene glycol; and
(c) 5 to 15% w/w of thermolysin,
wherein the dissolvable, gel-forming film has a water content of less than 15% w/w, and the dissolvable, gel-forming film is capable of forming a hydrogel when 1 gm of gel-forming film is contacted with 20 ml of water or other aqueous medium.
30. The dissolvable, gel-forming film of claim 29 , wherein the hydrogel that is formed has a viscosity of 1,000 to 100,000 cps, as measured using a Brookfield RV Model Viscometer using small sample adapter with spindle #SC4-14 and chamber #SC4-6R, at 10 rpm at room temperature, reading taken at 1 minute.
31. The dissolvable, gel-forming film of claim 29 , wherein the film is capable of dissolving in water at a rate from 0.5-10 mg/min.