TY - JOUR

T1 - Whey proteins as stabilizers in amorphous solid dispersions

AU - Mishra, Jaya

AU - Bohr, Adam

AU - Rades, Thomas

AU - Grohganz, Holger

AU - Löbmann, Korbinian

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - Amorphous

KW - Dissolution

KW - Poorly water-soluble drugs

KW - Solid dispersions

KW - Whey proteins

U2 - 10.1016/j.ejps.2018.12.002

DO - 10.1016/j.ejps.2018.12.002

M3 - Journal article

C2 - 30528387

AN - SCOPUS:85057751811

VL - 128

SP - 144

EP - 151

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

ER -