Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

摘要: The objective of the current study is to mechanistically differentiate dissolution and supersaturation behaviors amorphous drugs from solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink conditions through a direct head-to-head comparison. ASDs indomethacin (IND) were prepared in several polymers which exhibit different solubility acidic (pH 1.2) basic 7.4) media. selected range water-soluble (e.g., PVP Soluplus) water-insoluble ethylcellulose Eudragit RL PO) those only soluble an or medium E100, L100, HPMCAS). At 20 wt.% drug loading, DSC powder XRD analysis confirmed that majority incorporated IND was present state. Our results confirm whether carrier matrix determines release mechanism ASD systems has impact rate generation, thus turn affecting evolution systems. For example, conditions, governed by dissolution-controlled leading initial surge followed sharp decline concentration due rapid nucleation crystallization. In contrast, more gradual as regulated diffusion-controlled built up gradually sustained over extended period time without any apparent decline. Since tested can be switched insoluble simply changing pH medium, obtained here provide unequivocal evidence proposed transition kinetic profiles same system induced changes pH.