Whey proteins as stabilizers in amorphous solid dispersions.

Whey proteins are extensively used as nutritional supplements but have so far not been investigated as co-formers for amorphous solid dispersions (ASD) to enhance the solubility and dissolution rate of poorly water soluble drugs. In this study, whey protein isolate (WPI) and whey protein hydrolysate (WPH) were each mixed with three poorly water soluble drugs (indomethacin: IND, carvedilol: CAR and furosemide: FUR) and prepared as ASDs at 50% (w/w) drug loading using vibrational ball milling. Subsequently, solid state characteristics, dissolution rate and physical stability of the obtained samples were analyzed. All ASDs showed a significant increase in their glass transition temperatures, as well as faster dissolution rates and higher apparent solubilities compared to both the respective pure crystalline and amorphous drugs. The saturation solubility of the drugs was increased in the presence of the whey proteins, and the investigated ASDs showed supersaturation by attaining higher drug concentrations compared to the respective saturation solubilities. Upon storage, ASDs containing IND were found to be physically stable for at least 27 months, whereas, ASDs containing CAR or FUR were stable for about 8 months and 17 months, respectively. This was a tremendous increase in physical stability compared to the pure amorphous drugs which recrystallized within less than one week. Overall, WPI and WPH proved to be promising co-formers and amorphous stabilizers in ASD formulations.

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.