Dissolution rate enhancement of the anti-inflammatory drug diflunisal by coprecipitation with a biocompatible polymer using carbon dioxide as a supercritical fluid antisolvent

作者：Zahran Fouad; Cabanas Albertina; Cheda Jose A R; Renuncio Juan A R; Pando Concepcion^*

来源：Journal of Supercritical Fluids, 2014, 88: 56-65.

DOI：10.1016/j.supflu.2014.01.015

• Diflunisal
• dissolution rate enhancement
• drug-polymer interaction
• polyvinylpyrrolidone
• supercritical antisolvent

Dissolution rate enhancement of the anti-inflammatory drug diflunisal was achieved using for the first time a supercritical fluid technology. The supercritical fluid antisolvent (SAS) method was applied to precipitate diflunisal alone and to coprecipitate the drug together with the biocompatible polymer polyvinylpyrrolidone (PVP K-30 and K-10). The untreated and SAS processed diflunisal, and the coprecipitates were characterized in terms of size, morphology, crystallinity, compositions, drug-polymer interactions, and drug release. SAS processed diflunisal exhibited a polymorphic form different from that of the untreated drug. Diflunisal crystallinity disappeared in the coprecipitates. Three different drug: polymer mass ratios were studied: 75:25, 50:50, and 25:75. Microparticle size decreased and aggregation disappeared as the relative amount of polymer increased. The 25:75 coprecipitate consisted of loose spherical particles exhibiting mean particle size of 410 nm while the 75:25 coprecipitate consisted of bigger aggregated particles. The SAS method was shown to be a suitable technology to form solid dispersions of a poorly soluble drug.

• 出版日期2014-4