Formulation and Stability of ltraconazole and Odanacatib Nanoparticles: Governing Physical Parameters

被引：84

作者：

Kumar, Varun ^{[1
]}

Wang, Lei ^{[2
]}

Riebe, Mike ^{[2
]}

Tung, Hsien-Hsin ^{[2
]}

Prud'homme, Robert K. ^{[1
]}

机构：

[1] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA

[2] Merck Res Lab, West Point, PA 19486 USA

来源：

MOLECULAR PHARMACEUTICS | 2009年 / 6卷 / 04期

关键词：

Nanoparticle; nucleation; precipitation; solubility; stability; supersaturation; Ostwald ripening; itraconazole; odanacatib; poloxamer; DISSOLUTION RATES; GLASS-TRANSITION; DRUG;

D O I：

10.1021/mp900002t

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The successful formulation of itraconazole and odanacatib into nanoparticle form with diameters of 145 and 350 rim, 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.

引用

页码：1118 / 1124

页数：7

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