溶解
无定形固体
化学工程
溶解度
色散(光学)
材料科学
化学
有机化学
光学
物理
工程类
作者
Keisuke Ueda,Kenjirou Higashi,Kunikazu Moribe
标识
DOI:10.1016/j.ijpharm.2019.02.034
摘要
Drug-rich amorphous nanodroplets have great potential to improve intestinal absorption of poorly water-soluble drugs. Spray-dried samples (SPDs) of glibenclamide (GLB) with hypromellose (HPMC) or hypromellose acetate succinate (HPMC-AS, grade AS-LF and AS-HF) were prepared to investigate how GLB-rich amorphous nanodroplets form during the dissolution of solid dispersions. The co-spray drying of AS-LF significantly enhanced GLB dissolution from the SPD, leading to the temporary formation of GLB-rich amorphous nanodroplets. However, the droplets gradually coarsened as AS-LF fails to inhibit coarsening. In contrast, the addition of HPMC to the SPD failed to aid GLB-rich amorphous nanodroplet formation during dissolution. The failure of formation of GLB-rich amorphous nanodroplet was caused by slow GLB dissolution, due to the poor controllability of the GLB dissolution by HPMC. The addition of AS-HF to the SPD produced amorphous GLB particles that contained a large amount of AS-HF during dissolution. Gel-like particles formed instead of GLB-rich amorphous nanodroplets. When the SPD containing AS-LF was dissolved in AS-HF solution, stably-dispersed GLB-rich amorphous nanodroplets were successfully formed owing to rapid GLB dissolution from the SPD containing AS-LF and strong coarsening inhibition by AS-HF. Formulation optimization considering both aqueous dissolution of the solid dispersion and the inhibition of nanodroplet coarsening achieved stably-dispersed drug-rich amorphous nanodroplets.
科研通智能强力驱动
Strongly Powered by AbleSci AI