Solvent effects on the controlled dense gas precipitation of model proteins

Abstract

Protein was precipitated from organic and aqueous solutions using carbon dioxide and ammonia as antisolvents. The gas antisolvent precipitation process (GAS) was used to produce lysozyme, insulin and myoglobin powders. Protein powders were produced with narrow size ranges, and particle size was controlled between 0.05 mm and 2.0 mm by changes to the solvent system. Typically the stronger the protein solvent the larger the precipitate size. The GAS process, although ideal for the micronisation of stable protein powders, was limited by the number of suitable protein solvents that were miscible with dense carbon dioxide and that did not irreversibly affect protein conformation. As a result, GAS precipitation from aqueous solutions was also assessed. Insulin was precipitated from aqueous solutions as discrete 0.2±0.3 mm spheres using ammonia as an antisolvent.

Investigation into the mechanism of (−)-epigallocatechin-3-gallate-induced precipitation of insulin

“…Insulin is susceptible to forming ␤-sheet-rich fibrils upon exposure to elevated temperatures, low pH, and agitation [9][10][11]. The addition of organic solvents, such as ethyl acetate, dimethylsulfoxide [12], and tannic acid [13], however, precipitates insulin from aqueous solutions as globular aggregates [14].…”

Morphology and growth control of griseofulvin recrystallized by compressed carbon dioxide as antisolvent

“…Crystallization assisted by supercritical fluids is a promising operation for pharmaceutical industry, since it may lead to pharmaceutical compounds of improved availability [2][3][4][5][6], and enable the production of micro-particles for drug delivery [7][8][9][10][11][12]. CO 2 is the most widely used compressed antisolvent, because it is cheap, non-toxic, nonflammable.…”

Dense Gas Processing of Micron-Sized Drug Formulations Incorporating Hydroxypropylated and Methylated Beta-Cyclodextrin

“…The alternate spray/wash mode was implemented to limit the concentration of DMSO in the precipitation vessel because, as evidenced in other studies (17,18), the extraction of DMSO during DG antisolvent processing can be otherwise unsatisfactory. The spray/wash stages were repeated until the desired volume of solution was delivered to the system.…”