Nanoparticulate megestrol formulations

1. A method of increasing the body mass in a human patient suffering from anorexia, cachexia, or loss of body mass comprising administering to the human patient a megestrol acetate formulation, wherein:

(a) the megestrol acetate formulation is a dose of about 40 mg to about 800 mg in about a 5 mL dose of an oral suspension;

(b) the megestrol acetate formulation comprises megestrol acetate particles, wherein about 80% of the particles are between about 250 nm and about 50 nm, and at least one surface stabilizer is associated with the surface of the megestrol acetate particles; and

(c) the administration is once daily;

wherein after a single administration in a human subject of the formulation there is no substantial difference in the C max of megestrol when the formulation is administered to the subject in a fed versus a fasted state,

wherein fasted state is defined as the subject having no food within at least the previous 10 hours, and

wherein fed state is defined as the subject having a high-calorie meal within approximately 30 minutes of dosing.

2. The method of claim 1 , wherein about 80% of the particles are between about 230 nm and about 70 nm.

3. The method of claim 1 , wherein the anorexia, cachexia or loss of body mass is associated with a diagnosis of HIV or AIDS in the human patient.

4. The method of claim 1 , wherein the anorexia, cachexia or loss of body mass is associated with a diagnosis of cancer in the human patient.

5. The method of claim 1 , wherein there is a difference in the mean T max for the nanoparticulate megestrol acetate formulation when administered in fed versus fasted states, and that difference is selected from the group consisting of less than about 100%, less than about 90%, less than about 80%, less than about 70%, less than about 60%, less than about 50%, less than about 40%, less than about 30%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, and less than about 3%.

6. The method of claim 1 , wherein the formulation exhibits a mean C max , selected from the group consisting of greater than about 5%, greater than about 10%, greater than about 15%, greater than about 20%, greater than about 30%, greater than about 40%, greater than about 50%, greater than about 60%, greater than about 70%, greater than about 80%, greater than about 90%, greater than about 100%, greater than about 110%, greater than about 120%, greater than about 130% greater than about 140%, and greater than about 150% of the mean C max exhibited by a standard commercial, non-nanoparticulate composition of megestrol, administered at the same dosage.

7. The method of claim 1 , wherein there is a difference in absorption (AUC) when the formulation is administered in fed versus fasted states, and the difference is selected from the group consisting of less than about 35%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, and less than about 3%.

8. The method of claim 1 , wherein a maximum blood plasma concentration of megestrol is attained in about 1 hour or less after administration of the megestrol acetate formulation in fasting subjects.

9. The method of claim 1 , wherein a maximum blood plasma concentration of megestrol of at least about 700 ng/ml is obtained.

10. The method of claim 9 , wherein the maximum blood plasma concentration of megestrol is at least about 700 ng/ml and is attained in less than 5 hours after administration of the megestrol acetate formulation.

11. The method of claim 1 , wherein the maximum blood plasma concentration of megestrol is at least about 400 ng/ml and is attained in less than 5 hours after administration of the megestrol acetate formulation.

12. The method of claim 1 , wherein a mean C max of about 300 ng/ml to about 2000 ng/ml is obtained after a single administration of the formulation in the human subject in a fasted state.

13. The method of claim 1 , wherein the surface stabilizer is selected from the group consisting of nonionic surfactants, cationic surfactants, ionic surfactants, and zwitterionic surfactants.

14. The method of claim 1 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, sodium lauryl sulfate, dioctylsulfosuccinate, polyoxyethylene alkyl etherspolyoxyethylene sorbitan fatty acid esters, 4-(1,1,3,3-tetramethylbutyl)-phenol polymer with ethylene oxide and formaldehyde, lysozyme, and random copolymers of vinyl pyrrolidone and vinyl acetate.

15. The method of claim 14 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose, dioctylsulfosuccinate, and a combination thereof.

16. A method of increasing the body mass in a human patient suffering from anorexia, cachexia, or loss of body mass comprising administering to the human patient a megestrol acetate formulation, wherein:

(a) the megestrol acetate formulation is a dose of about 40 mg to about 800 mg in about a 5 mL dose of an oral suspension;

(b) the megestrol acetate formulation comprises megestrol acetate particles, wherein about 90% of the particles are less than or equivalent to about 250 nm, and about 10% of the particles are less than or equivalent to about 50 nm, and at least one surface stabilizer is associated with the surface of the megestrol acetate particles; and

(c) the administration is once daily;

wherein after a single administration in a human subject of the formulation there is no substantial difference in the C max of megestrol when the formulation is administered to the subject in a fed versus a fasted state,

wherein fasted state is defined as the subject having no food within at least the previous 10 hours, and

wherein fed state is defined as the subject having a high-calorie meal within approximately 30 minutes of dosing.

17. The method of claim 16 , wherein about 90% of the particles are less than or equivalent to about 230 nm, and about 10% of the particles are less than or equivalent to about 70 nm.

18. The method of claim 16 , wherein the anorexia, cachexia or loss of body mass is associated with a diagnosis of HIV or AIDS in the human patient.

19. The method of claim 16 , wherein the anorexia, cachexia or loss of body mass is associated with a diagnosis of cancer in the human patient.

20. The method of claim 16 , wherein the surface stabilizer is selected from the group consisting of nonionic surfactants, cationic surfactants, ionic surfactants, and zwitterionic surfactants.

21. The method of claim 16 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, sodium lauryl sulfate, dioctylsulfosuccinate, polyoxyethylene alkyl etherspolyoxyethylene sorbitan fatty acid esters, 4-(1,1,3,3-tetramethylbutyl)-phenol polymer with ethylene oxide and formaldehyde, lysozyme, and random copolymers of vinyl pyrrolidone and vinyl acetate.

22. The method of claim 21 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose, dioctylsulfosuccinate, and a combination thereof.

23. A method of increasing the body mass in a human patient suffering from anorexia, cachexia, or loss of body mass comprising administering to the human patient a megestrol acetate formulation, wherein:

(a) the megestrol acetate formulation is a dose of about 40 mg to about 800 mg in about a 5 mL dose of an oral suspension;

(b) the megestrol acetate formulation comprises megestrol acetate particles, wherein about 90% of the particles have a size less than or equivalent to about 250 nm and about 90% of particles have a size greater than or equivalent to about 50 nm, and at least one surface stabilizer is associated with the surface of the megestrol acetate particles; and

(c) the administration is once daily;

wherein after a single administration in a human subject of the formulation there is no substantial difference in the C max of megestrol when the formulation is administered to the subject in a fed versus a fasted state,

wherein fasted state is defined as the subject having no food within at least the previous 10 hours, and

wherein fed state is defined as the subject having a high-calorie meal within approximately 30 minutes of dosing.

24. The method of claim 23 , wherein about 90% of the particles have a size less than or equivalent to about 230 nm and about 90% of particles have a size greater than or equivalent to about 70 nm.

25. The method of claim 23 , wherein the anorexia, cachexia or loss of body mass is associated with a diagnosis of HIV or AIDS in the human patient.

26. The method of claim 23 , wherein the anorexia, cachexia or loss of body mass is associated with a diagnosis of cancer in the human patient.

27. The method of claim 23 , wherein the surface stabilizer is selected from the group consisting of nonionic surfactants, cationic surfactants, ionic surfactants, and zwitterionic surfactants.

28. The method of claim 23 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, sodium lauryl sulfate, dioctylsulfosuccinate, polyoxyethylene alkyl etherspolyoxyethylene sorbitan fatty acid esters, 4-(1,1,3,3-tetramethylbutyl)-phenol polymer with ethylene oxide and formaldehyde, lysozyme, and random copolymers of vinyl pyrrolidone and vinyl acetate.

29. The method of claim 19 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose, dioctylsulfosuccinate, and a combination thereof.