Fenretinide formulations, systems incorporating same, and methods for their use

1 . A formulation comprising:

(a) about 10 wt. % to about 20 wt. % fenretinide;

(b) about 6 wt. % to about 9 wt. % propylene glycol;

(c) about 12 wt. % to about 18 wt. % menthol;

(d) about 20 wt. % to about 25 wt. % polyvinyl pyrrolidone;

(e) about 3 wt. % to about 8 wt. % triethyl citrate;

(f) about 10 wt. % to about 20 wt. % triethyl-2-acetylcitrate; and

(g) about 15 wt. % to about 25 wt. % hydroxypropyl cellulose,

wherein the weight percents are based on the total weight of the formulation excluding any volatile ingredients.

2 . The formulation according to claim 1 , wherein the formulation comprises:

(a) about 15 wt. % fenretinide;

(b) about 7.5 wt. % propylene glycol;

(c) about 15 wt. % menthol;

(d) about 20 wt. % polyvinyl pyrrolidone;

(e) about 5 wt. % triethyl citrate;

(f) about 15 wt. % triethyl-2-acetylcitrate;

(g) about 20 wt. % hydroxypropyl cellulose; and

(h) about 2.5 wt. % of a nonionic surfactant;

wherein the weight percent of each ingredient in the formulation is based on the total weight of the formulation excluding any volatile ingredients.

3 . The formulation according to claim 2 , wherein the formulation is in the form of a film.

4 . The formulation according to claim 3 , wherein the film has an average thickness of about 0.1 mm to about 0.2 mm.

5 . A mucoadhesive delivery system comprising:

(a) a backing layer, and

(b) a formulation comprising:

(i) about 10 wt. % to about 20 wt. % fenretinide;

(ii) about 6 wt. % to about 9 wt. % propylene glycol;

(iii) about 12 wt. % to about 18 wt. % menthol;

(iv) about 20 wt. % to about 25 wt. % polyvinyl pyrrolidone;

(v) about 3 wt. % to about 8 wt. % triethyl citrate;

(vi) about 10 wt. % to about 20 wt. % triethyl-2-acetylcitrate; and

(v) about 15 wt. % to about 25 wt. % hydroxypropyl cellulose,

wherein the weight percents are based on the total weight of the formulation excluding any volatile ingredients.

6 . The system of claim 5 , wherein the formulation comprises:

(i) about 15 wt. % fenretinide;

(ii) about 7.5 wt. % propylene glycol;

(iii) about 15 wt. % menthol;

(iv) about 20 wt. % polyvinyl pyrrolidone;

(v) about 5 wt. % triethyl citrate;

(vi) about 15 wt. % triethyl-2-acetylcitrate,

(vii) about 20 wt. % hydroxypropyl cellulose; and

(viii) about 2.5 wt. % of a nonionic surfactant;

wherein the weight percent of each ingredient in the formulation is based on the total weight of the formulation excluding any volatile ingredients.

7 . The system of claim 6 , wherein the formulation is in the form of a film having a thickness of about 0.1 mm to about 0.2 mm.

8 . A formulation consisting of:

(a) about 15 wt. % fenretinide;

(b) about 7.5 wt. % propylene glycol;

(c) about 15 wt. % menthol;

(d) about 20 wt. % polyvinyl pyrrolidone;

(e) about 5 wt. % triethyl citrate;

(f) about 15 wt. % triethyl-2-acetylcitrate;

(g) about 20 wt. % hydroxypropyl cellulose; and

(h) about 2.5 wt. % of a nonionic surfactant;

wherein the weight percent of each ingredient in the formulation is based on the total weight of the formulation excluding any volatile ingredients.

9 . A mucoadhesive delivery system comprising:

(a) a backing layer, and

(b) a formulation consisting of:

(i) about 10 wt. % to about 20 wt. % fenretinide;

(ii) about 6 wt. % to about 9 wt. % propylene glycol;

(iii) about 12 wt. % to about 18 wt. % menthol;

(iv) about 20 wt. % to about 25 wt. % polyvinyl pyrrolidone;

(v) about 3 wt. % to about 8 wt. % triethyl citrate;

(vi) about 10 wt. % to about 20 wt. % triethyl-2-acetylcitrate;

(vii) about 15 wt. % to about 25 wt. % hydroxypropyl cellulose; and

(viii) about 2.5 wt. % of a nonionic surfactant;

wherein the weight percents are based on the total weight of the formulation excluding any volatile ingredients.

10 . The composition of claim 1 , wherein the hydroxypropyl cellulose in the formulation has an average MW of about 200,000 to about 300,000.

11 . A method for the treatment of a patient afflicted with a precancerous lesion in the stratified squamous epithelium of mucosal tissue comprising:

a) Providing the mucoadhesive delivery system of claim 1 ;

b) Applying the formulation onto the precancerous lesion.

12 . The method of claim 11 , wherein the formulation is applied onto the precancerous lesion for between about 1 and about 60 minutes.

13 . The method of claim 12 , wherein the formulation is applied onto the lesion at least once per week for between 1 and 12 weeks.

14 . The method of claim 11 , wherein the hydroxypropyl cellulose in the formulation has an average MW of about 200,000 to about 300,000.

15 . The method of claim 11 , wherein the formulation is in the form of a film.

16 . The method of claim 15 , wherein the film has an average thickness of about 0.1 mm to about 0.2 mm.