Preparation and characterization of efavirenz cocrystal-encapsulated pronanoliposomes for antiretroviral therapy with improved bioavailability†

Abstract

The present research work aims to improve the bioavailability of the antiretroviral drug efavirenz (EFV) using pharmaceutical cocrystallization technique. EFV is a potential antiretroviral drug that exhibits extremely poor water solubility and poor oral bioavailability and falls under the BCS-II category. EFV and L-proline were selected in a 1 : 1 equimolar ratio to formulate efavirenz proline co-crystals, and a facile method was adopted to prepare co-crystals of EFV. The formation of a new solid phase was confirmed through advanced techniques such as Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and powder X-ray diffraction (pXRD) analysis, and solubility study was conducted utilising UV visible spectroscopy. Proliposomal vesicles containing EFV or EFV cocrystals were prepared using thin film hydration methods with few modifications. The vesicle size in dispersion, zeta potential, surface morphology, drug loading and in vitro drug release were assessed. Co-crystallization increased the solubility of EFV up to 3 fold, and the liposomes were found to release the drug in a sustained manner. The optimized formulation was found to have a substantial amount of EFV loading (32.70%) and entrapment efficiency (99.28%) with a narrow range of size distribution. The liposomes containing the pure drug showed 72% release of the drug in 72 h, whereas the liposomes containing co-crystals showed 99.98% release of the drug in 72 h. This was due to the presence of L-proline in association with EFV, which led to an enhancement in the polarity of hydrophobic EFV, thus increasing its dissolution in drug release media. The present work reports a cost-effective method for the enhancement of drug solubility, providing sustained drug release from liposome and thereby improving the oral bioavailability of the antiviral agent EFV.