Ganciclovir (GCV) is only slightly soluble in water and hence oral GCV gives low absolute bioavailability. Liquid precipitation is an effective way to prepare micro-sized drug particles. The solubility of GCV in several solvents or in aqueous solution at different pH values was determined. According to its solubility behavior, reactive precipitation was suggested as the micronization method of GCV. The mean particle diameter of micronized GCV powder was around 15~20 μm, smaller than that of raw GCV powder, and the size distribution of micronized GCV was narrower than that of raw GCV. The stirring rate, the type and addition of stabilizing agents seemed to have no significant effect on the particle size of micronized GCV. Micronized GCV showed much faster dissolution rate than raw GCV.

Enantiopure nipecotic acid or ethyl nipecotate are key precursors for synthesizing a variety of pharmaceutically important compounds. In this work a two-step resolution of racemic ethyl nipecotate was developed to prepare enantiopure (S)-ethyl nipecotate. In the enzymatic resolution step, six lipases were screened for their ability to enantioselectively hydrolyze rac-ethyl nipecotate in t-butanol at 30°C and Novozym 435 was found to be the most effective. Solvent effects on the hydrolysis conversion and enantioselectivity showed that water was the optimum medium. When rac-ethyl nipecotate concentration was kept at 0.5M, the hydrolysis under optimum conditions (lipase loading 5mg/mL, phosphate buffer pH 7.0, reaction temperature 30°C, reaction time 6h) afforded 68.9% ees and 69.5% eep at 49.8% conversion. Novozym 435 preferentially hydrolyzed (R)-ethyl nipecotate over (S)-enantiomer. A parallel reaction model was suggested and found to fit the experimental initial rate data very well. (S)-enriched ethyl nipecotate was further resolved using (D)-tartaric acid and enantiopure (S)-ethyl nipecotate (98.5% ee) was acquired in 84.3% yield. The overall yield of enantiopure (S)-ethyl nipecotate by this two-step resolution was up to 36.0%.