ETOPOSIDE AMORPHOUS SOLID DISPERSION FOR IMPROVED ORAL BIOAVAILABILITY: FORMULATION, CHARACTERIZATION, PHARMACOKINETIC AND CYTOTOXICITY STUDIES

Abstract

Etoposide is a well-known anti-tumor agent used to treat a variety of cancers. Although it is a BCS class IV drug, applications are restricted due to poor solubility and bioavailability. Hence, the current research was designed to overcome these pitfalls. A total of 16 formulation batches were developed using the physical mixture and kneading method and optimized by Design-expert® software. A selected batch was evaluated using solubility, differential scanning calorimetry, X-ray diffraction, motic microscopy, scanning electron microscopy, Fourier transform infrared (FtIR), gastrointestinal distribution, pharmacokinetic and cytotoxicity study. the results showed that the saturated solubility of formulation was 19.76 mg mL -1. FtIR showed C-O=1646 cm -1, and C-H=2956 cm -1. the distribution study indicated 9.11, 5.39 and 4.23 μg mL-1 colon concentrations at 8h, 16h, and 24h, respectively. the Cmax and AUC were found at 741.17±12.29 ng mL-1 and 3089.23 ±34.69 ng mL -1 with less viability on HeLa cells. therefore, the study investigates the developed solid dispersions enhanced solubility and bioavailability with an antiproliferative effect.