Solid dose nanoparticulate compositions comprising a synergistic combination of a polymeric surface stabilizer and dioctyl sodium sulfosuccinate
AssigneeElan Pharma International Limited
InventorsNiels P. Ryde, Stephen B. Ruddy
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Abstract
Disclosed are solid dose nanoparticulate compositions comprising a poorly soluble active agent, at least one polymeric surface stabilizer, and dioctyl sodium sulfosuccinate (DOSS). The solid dose compositions exhibit superior redispersibility of the nanoparticulate composition upon administration to a mammal, such as a human or animal. The invention also describes methods of making and using such compositions.
Claims34
A solid dose nanoparticulate composition comprising:
- (a) an active agent which has a solubility in a liquid dispersion medium of less than about 10 mg/mL;
- (b) at least one polymeric surface stabilizer adsorbed on the surface of the active agent;
- and
- (c) about 0.1% to about 20% w/w, of dioctyl sodium sulfosuccinate (DOSS),
- wherein the effective average particle size of the nanoparticulate dispersion prior to incorporation in the solid dose formulation, comprising said poorly soluble active agent and at least one polymeric surface stabilizer, is less than about 1 micron, and upon reconstitution in media representative of human physiological conditions, the solid dose nanoparticulate composition redisperses such that 90% of the active agent particles have a particle size of less than about 5 microns.
A method of making a solid dose nanoparticulate composition having a high redispersibility upon administration to a mammal comprising:
- (a) dispersing particles of an active agent which has a solubility in a liquid dispersion medium of less than about 10 mg/mL in a liquid dispersion medium;
- (b) applying mechanical means in the presence of grinding media to reduce the effective average particle size of the active agent in the liquid dispersion medium to less than about 1 micron, wherein at least one polymeric surface stabilizer and dioctyl sodium sulfosuccinate are added to the liquid dispersion medium before or after milling;
- (c) drying the nanoparticulate dispersion comprising an active agent, at least one polymeric surface stabilizer, and dioctyl sodium sulfosuccinate;
- and
- (d) formulating the dry nanoparticulate composition into a solid dose form for administration,
- wherein upon reconstitution in media representative of human physiological conditions, the solid dose nanoparticulate composition redisperses such that 90% of the active agent particles have a particle size of less than about 5 microns.
A method of treating a patient in need with a solid dose nanoparticulate composition having high redispersibility of the nanoparticulate composition upon administration to a mammal, comprising administering to a patient in need a therapeutically effective amount of a solid dose nanoparticulate composition comprising:
- (a) an active agent which has a solubility in a liquid dispersion medium of less than about 10 mg/mL;
- (b) at least one polymeric surface stabilizer adsorbed on the surface of the active agent;
- and
- (c) about 0.1% to about 20% w/w of dioctyl sodium sulfosuccinate (DOSS),
- wherein the effective average particle size of the nanoparticulate dispersion prior to incorporation in the solid dose formulation, comprising said poorly soluble active agent and at least one polymeric surface stabilizer, is less than about 1 micron, and upon reconstitution in media representative of human physiological conditions, the solid dose nanoparticulate composition redisperses such that 90% of the active agent particles have a particle size of less than about 5 microns.
Dependencies are inferred from the claim text.