Nanoparticulate compositions comprising amorphous cyclosporine and methods of making and using such compositions
AssigneeElan Pharma International Limited
InventorsH. William Bosch, Kevin D. Ostrander, Douglas C. Hovey
Life of this patent
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Abstract
Nanoparticulate amorphous cyclosporine formulations, and nanoparticulate cyclosporine formulations comprising a mixture of amorphous and crystalline cyclosporine, having effective average particle sizes of less than about 2000 nm are described. The compositions exhibit increased bioavailability and increased consistency of bioavailability as compared to prior macro-sized cyclosporine and formulations. Methods of making and using the compositions are also described.
Claims59
A nanoparticulate composition comprising:
- (a) amorphous cyclosporin particles;
- and
- (b) at least one non-crosslinked surface stabilizer adsorbed on the surface of the cyclosporin particles,
- wherein:
- (i) the cyclosporin particles have an effective average particle size of less than about 2000 nm, and (ii) the cyclosporin and at least one surface stabilizer are present in a ratio of about 10:1 to about 1.5:1 (w/w), cyclosporin to surface stabilizer and (iii) the nanoparticulate composition does no contain an alcohol solubilizing agent and (iv) wherein the nanoparticulate composition does not contain solvent residues resulting from solvent extraction, solvent precipitation, or solvent-mediated hydrosol formation.
A nanoparticulate composition comprising:
- (a) a mixture of amorphous and crystalline cyclosporin particles;
- and
- (b) at least one non-crosslinked surface stabilizer absorbed on the surface of the cyclosporin particles,
- wherein:
- (i) the cyclosporin particles have an effective average particle size of less than about 2000 nm, and (ii) the cyclosporin and at least one surface stabilizer are present in a ratio of about 10:1 to about 1.5:1 (w/w), cyclosporin to surface stabilizer and (iii) the nanoparticulate composition does no contain an alcohol solubilizing agent and (iv) wherein the nanoparticulate composition does not contain solvent residues resulting from solvent extraction, solvent precipitation, or solvent-mediated hydrosol formation.
A method of making a nanoparticulate composition comprising:
- (a) amorphous cyclosporin particles;
- and
- (b) at least one non-crosslinked surface stabilizer absorbed on the surface of the cyclosporin particles,
- wherein:
- (i) the cyclosporin particles have an effective average particle size of less than about 1000 nm, and (ii) the cyclosporin and the at least one surface stabilizer are present in a ratio of about 10:1 to about 1.5:1 (w/w), cyclosporin to surface stabilizer,
- said method comprising contacting cyclosporin with at least one non-crosslinked surface stabilizer for a time and under conditions sufficient to provide a nanoparticulate amorphous cyclosporin composition in which the cyclosporin particles have an average effective particle size of less than about 2000 nm and the composition has a drug to surface stabilizer ratio of about 10:1 to about 1.5:1 (w/w), cyclosporin to surface stabilizer and (iii) the nanoparticulate composition does no contain an alcohol solubilizing agent and (iv) wherein the nanoparticulate composition does not contain solvent residues resulting from solvent extraction, solvent precipitation, or solvent-mediated hydrosol formation.
Dependencies are inferred from the claim text.