Preparation and in vitro Evaluation of Inclusion Complexes of Nelfinavir with Chemically Modified β-cyclodextrins

Abstract

Nelfinavir is a poorly water-soluble antiretroviral drug with relatively low bioavailability. In the
present study, the practically insoluble drug, nelfinavir (NFV) and its inclusion complexes with hydroxypropyl-β-
cyclodextrin (HP-β-CD) were investigated to improve the aqueous solubility and the dissolution rate of the drug, thus
enhancing its bioavailability. The phase solubility diagram with HP-β-CD was classified as AL-type at all
temperatures investigated, indicating the formation of higher order complexes. The apparent complexation constants
(K1:1) calculated from phase solubility diagram were 145.49, 188.45 and 255.54 M-1 at 25, 37 and 45 ± 0.50C,
respectively. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably
increased; this could be mainly attributed to the improved solubility and dissolution associated with inclusion
complex between drug and HP- β -CD. Absence of endothermic and characteristic diffraction peaks corresponding to
NFV was observed for the inclusion complex in DSC and PXRD. FT-IR study indicated that the presence of
intermolecular hydrogen bonds between NFV and HP-β-CD in inclusion complex, resulting in the formation of
amorphous form.