Enhancement of Bioavailability of Non-nucleoside Reverse Transciptase Inhibitor Using Nanosponges

Abstract

Efavirenz is a non-nucleoside reverse transcriptase inhibitor which is chronically prescribed for HIV patients. However, it exhibits solubility-limited bioavailability. Aim of this work was to enhance the solubility and dissolution of the Biopharmaceutical Classification System (BCS) class II drug efavirenz, using beta-cyclodextrin-based nanosponges. Nanosponges have high drug loading capacity and are effective for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonates in different ratios to prepare nanosponges. The nanosponges were loaded with efavirenz by solvent evaporation method and the nanosponge with higher drug loading capacity was selected for further studies. Binary and ternary complexes with EFA, NS, and PVP K30 were prepared and characterized by phase solubility, solution state interaction, saturation solubility, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and field emission scanning electron microscopy was performed. Results obtained from spectral characterization confirmed inclusion complexation. Stability constant for ternary complex was found to be 1997 lit/mole, which indicates stable complex formation. The saturation solubility was found to be 17-fold higher with ternary complex in distilled water and about 4-fold in simulated gastric fluid. In vitro dissolution was improved 3 folds with ternary complex. Ternary nanosponge complexes were found to have 2-fold increase in oral bioavailability of efavirenz as compared to plain drug.

Keywords: beta-cyclodextrin; bioavailability; inclusion complex; nanosponges; solubility enhancement.