Characterization of solvent induced crystalline and amorphous homoharringtonine

Abstract

The morphologies of homoharringtonine were conveniently controlled by solvent treatment and the morphologies of homoharringtonine were characterized by XRD and SEM. Crystalline homoharringtonine was simply made by dissolving homoharringtonine in a special polar solvent containing a small amount of water (methanol/water= 98/2, v/v). On the other hand, amorphous homoharringtonine was made by dissolving homoharringtonine in relatively non-polar solvent (methylene chloride/methanol=98/2, v/v). Amorphous homoharringtonine, with a fine particle size, was obtained by dissolving in methylene chloride/methanol (98/2, v/v), following by spray drying. Also, residual solvents, methanol and methylene chloride, were easily removed to less than concentration limit in ICH (International Conference on Harmonisation) guidance by spray drying and successive drying in a vacuum oven. Amorphous homoharringtonine was more soluble in water than crystalline homoharringtonine, and the water content of amorphous homoharringtonine was less changeable than crystalline homoharringtonine at given humidity (95 RH%) during storage. This information is very useful for production and quality control of pharmaceuticals in the commercialization step.

Establishment of a solvent map for formation of crystalline and amorphous paclitaxel by solvent evaporation process

“…This result agrees with that for nevirapine, an API with a very low solubility in water; the higher the polarity index of the solvent, the higher the degree of crystallinity [27]. Since crystal shape may vary according to the evaporation rate of a solvent [28], the effect of this parameter was examined using acetonitrile at different temperatures (30,40, and 50 o C), which can affect the evaporation rate. Almost no change in the degree of crystallinity due to differences in evaporation rate was evident in the XRD pattern (data not shown).…”

“…To determine the effect of the evaporation rate on paclitaxel crystal shape, solvent evaporation was conducted with acetonitrile at different temperatures (30,40, and 50 o C). The sample was evaporated in a vacuum dryer for 24 h at each temperature, then analyzed by XRD.…”

“…This phenomenon appears to be associated with the degree of supersaturation of paclitaxel in the organic solvent used in the solvent evaporation process. For APIs, smaller final products have higher utilization value because small size is advantageous in terms of removal of residual solvent and solubility [29,30].…”

Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles – Part II. Physicochemical characterisation of spray-dried materials

“…It measures the onset relative humidity for a glass transition and crystallization processes in amorphous or partially amorphous materials, a useful parameter describing stability of solid-state forms. [12] Despite a number of theoretical studies on evaporation in spray-drying very little experimental data has been published on the residual solvent levels in spray-dried APIs [9,16] and this aspect of the process requires additional attention. This report therefore aim to investigate the solid-state physicochemical transformations of two model hydrophilic compounds, chlorothiazide sodium (CTZNa) [17] and potassium (CTZK), [18] on spray-drying and their subsequent characteri-sation in terms of residual solvent content and physical stability.…”