Comparison of improvements of aqueous dissolution of structurally analogous hydrophobic drugs by amorphous solid dispersion

Abstract

Amorphous solid dispersion (ASD) technique is promising to increase the dissolution of hydrophobic drug in aqueous solution systems, including in vivo. However, there is a serious lack of understanding of the impact of the molecular characteristics of a hydrophobic drug on the aqueous dissolution behavior of the drug from the ASD. This is because there are many structural differences between different types of drugs, which crucially complicates our understanding of the impact of each structural difference on the drug dissolution behavior. Hence, in this study, systematically different molecular structures of model drugs (ibuprofen, IBP, and its congeners) were employed to be solid-dispersed and their aqueous dissolution profiles were compared. Amorphous solid dispersions of the model drugs were prepared by a sole-amorphous sugar-based solid dispersion, SAS-SD, in which drug carrier is comprised solely of sugar. Aqueous dissolution profiles of the drugs were characterized using the maximum concentration (Cmax) and the time-integrated concentration of the dissolved drug (AUC60min). Comparisons of the dissolution profiles and thermal characteristics of the IBP congeners revealed that the IBP congener with a lower melting point (Tm) exhibited a greater improvement in the Cmax and AUC60min by the SAS-SD. Heat treatment of SAS-SD samples at 120° C for 60 min were conducted to further improve the drug dissolution. The results indicated an enhanced increase in the dissolution of two IBP congeners whose Tm = 97°C and 117° C but no significant effect for higher Tm congeners. Based on these findings, the issue of how the drug Tm affects the improvement in the drug dissolution by the SAS-SD and heat treatment is discussed.