Nanosuspensions for the formulation of poorly soluble drugs - I. Preparation by a size-reduction technique

被引:390
作者
Muller, RH [1 ]
Peters, K [1 ]
机构
[1] Free Univ Berlin, Dept Pharmaceut Biopharmaceut & Biotechnol, D-12169 Berlin, Germany
关键词
poorly soluble drugs; dissolution velocity; nanoparticle; high pressure homogenization; nanosuspension; solubility;
D O I
10.1016/S0378-5173(97)00311-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A basic problem of poorly soluble drugs is often an insufficient bioavailability. To allow the i.v. injection of these drugs, they were formulated as nanosuspensions by high pressure homogenization. The effect of the production parameters pressure and cycle number on the mean particle size and on the polydispersity of the nanosuspension was investigated with special attention to contamination by microparticles - the limiting factor for i.v. injection. Properties of the nanosuspensions are increased saturation solubility C(s) and dissolution rate dc/dt. These phenomena are explained using the Prandtl and the Ostwald-Freundlich equations. These properties promote the dissolution of the nanosuspensions in the blood after i.v. injection. The size distribution obtained and the use of an APV Gaulin homogenizer (FDA approved for parenterals) lead to a pharmaceutical product considered acceptable by the regulatory authorities. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:229 / 237
页数:9
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