Formulation and stability of itraconazole and odanacatib nanoparticles: governing physical parameters.
The successful formulation of itraconazole and odanacatib into nanoparticle form with diameters of 145 and 350 nm, respectively, using rapid, block copolymer-directed precipitation is presented. These are the smallest stable nanoparticles that have been reported for these compounds. The difference in size of the nanoparticles for the two compounds is explained by the difference in nucleation rate and its dependence on supersaturation. The conditions for stability after formation are presented: storage at 5 degrees C and removal of residual processing solvent. These requirements are explained in terms of solute solubility and its dependence on both temperature and solvent concentration. The theory of Ostwald ripening provides the framework for understanding the differences in stability observed for the two compounds. The dynamics of the hydrophobic polymer block plays a major role in long-term stability as demonstrated by the behavior of nanoparticles stabilized by poloxamer vs polystyrene-b-polyethylene oxide polymers.
Chemical Engineering Department, Princeton University, Princeton New Jersey 08544, USA.
Varun
V
Kumar
Lei
L
Wang
Mike
M
Riebe
Hsien-Hsin
HH
Tung
Robert K
RK
Prud'homme
D000935:Antifungal Agents / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D017964:Itraconazole / Q000737:chemistry*; D053758:Nanoparticles; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties
D000935:Antifungal Agents; D001713:Biphenyl Compounds; D011108:Polymers; D011137:Polystyrenes; C541965:polystyrene-b-poly(ethylene oxide); D020442:Poloxamer; D017964:Itraconazole; D011092:Polyethylene Glycols; C527128:odanacatib