PREFORMULATION STUDY OF ETOPOSIDE .2. INCREASED SOLUBILITY AND DISSOLUTION RATE BY SOLID-SOLID DISPERSIONS

Etoposide, an anticancer drug, has low and erratic oral bioavailability which is due to low aqueous solubility, slow dissolution rate and instability in acidic pH. The study objective was to enhance the aqueous solubility and dissolution rate of etoposide by solid-state modifications, which was attempted by preparation of solid-solid dispersions by coprecipitating the drug with polyethylene glycols (PEG) of different molecular weights in various ratios. The solubility and dissolution rate of etoposide from the coprecipitates were evaluated. The coprecipitate of etoposide with PEG 8000 (1:10. PEG weight fraction of 0.91) increased its solubility 2-fold and dissolution rate 42-fold (190.7 mu g/ml and 0.42 mg/min per cm(2) vs 93.8 mu g/ml and 0.01 mg/min per cm(2) of etoposide pure powder, respectively). The coprecipitates with other PEGs (PEG 1500, PEG 3400, PEG 6000) and PVP 40000 also increased etoposide dissolution rate to a great extent.