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 ± 0.5°C, 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.