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

• Supercritical fluid antisolvent (SAS) micronization is used to obtain diflunisal and diflunisal/PVP K-30 composites.
• Composites exhibit spherical morphologies with diameters ranging from 0.4 to 8 μm.
• Crystallinity, compositions, drug-polymer interactions, and drug release are studied.
• Application of SAS to the pure drug leads to a change in its polymorphic form.
• Diflunisal dissolution rate enhancement is attained using PVP in conjunction with SAS.

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.

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