Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir

The aim of this study was to prepare and characterize an hydroxypropyl-beta -cyclodextrin-saquinavir inclusion complex with the purpose of incorporati ng this complex into poly(alkylcyanoacrylate) nanoparticles in order to inc rease the drug loading. Hydroxypropyl-beta -cyclodextrin-saquinavi complex was characterized by thermal (differential scanning calorimetry), crystallo graphic (X-ray diffractography) and spectroscopic methods (circular dichroi sm, H-1-NMR). Nanoparticles were prepared by polymerization of alkylcyanoac rylate monomers (isobutyl- and isohexylcyanoacrylate) in a water solution o f the complex and further characterized. The apparent solubility of saquina vir was increased 400-fold at pH 7.0 in presence of hydroxypropyl-beta -cyc lodextrin owing to the formation of a drug-cyclodextrin complex as demonstr ated mainly by H-1 NMR and confirmed by other techniques. Saquinavir-loaded nanoparticles could be easily prepared in the presence of a drug-cyclodext rin complex. It was found that large amounts of cyclodextrins remained asso ciated with the particles, resulting in a 70-fold increase in saquinavir lo ading compared to nanoparticles prepared in the absence of cyclodextrins. T his study has shown that the loading in saquinavir of poly(alkylcyanoacryla te) nanospheres could be dramatically improved by simultaneously increasing the apparent solubility of the drug in the preparation medium and the amou nt of cyclodextrin associated with the particles, making these nanospheres a promising system for oral application. (C) 2001 Elsevier Science B.V. All rights reserved.