溶解
无定形固体
悬挂(拓扑)
材料科学
粒径
纳米颗粒
化学工程
降水
溶解度
色散(光学)
剂型
结块
胶体
水溶液
溶解试验
粒子(生态学)
色谱法
纳米技术
化学
有机化学
复合材料
数学
物理
生物制药分类系统
光学
海洋学
同伦
地质学
气象学
纯数学
工程类
作者
Hardeep S. Oberoi,Freddy Arce,Hitesh S. Purohit,Min Yu,Craig A. Fowler,Deliang Zhou,Devalina Law
标识
DOI:10.1016/j.xphs.2022.10.002
摘要
Amorphous solid dispersions (ASD) are a commonly used enabling formulation technology to drive oral absorption of poorly soluble drugs. To ensure adequate solid-state stability and dissolution characteristics, the ASD formulation design typically has ≤ 25% drug loading. Exposed to aqueous media, ASD formulations can produce drug-rich colloidal dispersion with particle size < 500 nm. This in situ formation of colloidal particles requires incorporation of excess excipients in the formulation. The concept of using engineered drug-rich particles having comparable size as those generated by ASDs in aqueous media is explored with the goal of increasing drug loading in the solid dosage form. Utilizing ABT-530 as model compound, a controlled solvent-antisolvent precipitation method resulted in a dilute suspension that contained drug-rich (90% (w/w)) amorphous nanoparticles (ANP). The precipitation process was optimized to yield a suspension containing < 300 nm ANP. A systematic evaluation of formulation properties and process variables resulted in the generation of dry powders composed of 1–8 µm agglomerates of nanoparticles which in contact with water regenerated the colloidal suspension having particle size comparable to primary particles. Thus, this work demonstrates an approach to designing a re-dispersible ANP based powder containing ≥90% w/w ABT-530 that could be used in preparation of a high drug load solid dosage form.
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