Characteristics of polymers enabling nano-comminution of water-insoluble drugs

Abstract

Comminution has evolved into an effective method to prepare drug nanoparticles. Although nano-comminution has advantages, such as cost-effectiveness and easy scale-up, the processing is significantly sensitive to the selection of a polymeric stabilizer, which suffers from a lack of systematic understanding in this field. Herein, the combinations of various water-insoluble drugs and pharmaceutical polymers were systematically compared to assess the general relationships between the properties of the drugs and polymers. As a rule of thumb, drugs of high molecular weight, low solubility, high melting points, and a surface energy similar to that of the polymers, can be successfully processed into nanoparticles of unimodal particle size distribution. The addition of small molecular weight surfactants results in an additional size reduction in certain polymer/drug pairs, generally by reducing the size of larger particles. Both anionic and cationic surfactants produce similar size reductions in a polymer/drug pair indicating that the charge-charge interaction between polymer and surfactant is not important. (C) 2007 Elsevier B.V. All rights reserved.