Preparation and Bioavailability Evaluation of Micronized Steroidal Mecigestone Drug Substance

Abstract

Microcrystals of 6α-methyl-16α,17α-cyclohexapregn-4-ene-3,20-dione (mecigestone) that differed from the starting drug substance by decreased sizes and altered morphologies were produced using a Nano Spray Dryer B-90 (Buchi, Switzerland) that allowed operation with organic solvents in a closed cycle. The bioavailability of starting crystalline and micronized mecigestone drug substance was studied by oral administration to laboratory white rats. Mecigestone was extracted from rat blood serum using solvent extraction. The extraction coefficient was 64%. The detection limit of the drug substance was 0.08 ng/mL. The content of unaltered mecigestone in the extracts was determined using HPLC with high-resolution mass spectrometric detection. Micronized mecigestone was 7.5 times more bioavailable than the starting drug substance.