Pharmaceutical Research ( IF 3.7 ) Pub Date : 2020-09-10 , DOI: 10.1007/s11095-020-02909-6 Asmita Adhikari 1 , James E Polli 1
Purpose
The objective was to characterize hydroxypropyl methylcellulose acetate succinate (HMPCAS) grades L, M, and H to enhance itraconazole (ITZ) release and permeation from spray dried dispersions (SDDs), and to investigate underpinning molecular ITZ-HPMCAS interactions that differentiated grade performance.
Methods
ITZ or its SDDs were subjected to solution stabilization assessment, one-dimensional proton nuclear magnetic resonance (NMR) spectroscopy, saturation transfer difference NMR studies, small volume dissolution, solid state transformation studies, and in vitro dissolution/permeation flux studies.
Results
HPMCAS-L was the best performing grade overall and exhibited greatest ITZ supersaturation concentration, small volume dissolution, and in vitro dissolution/permeation flux. Meanwhile, H grade retarded ITZ precipitation to the greatest extent in solution stabilization studies and exhibited greater hydrophobic interaction with ITZ in NMR studies. However, this apparent advantage of H grade through hydrophobic interactions between drug-polymer appeared to limit overall dissolution/permeation performance of SDD.
Conclusions
In vitro SDD studies and drug-polymer interaction studies provided insight into the performance of HPMCAS grades, as well as the relative contributions of various mechanisms that polymer can promote ITZ absorption from SDD.
中文翻译:
基于过饱和动力学和影响制剂性能的分子相互作用,表征伊曲康唑HPMCAS喷雾干燥分散体的等级。
目的
目的是表征羟丙基甲基纤维素乙酸琥珀酸酯(HMPCAS)的L,M和H级,以提高伊曲康唑(ITZ)从喷雾干燥分散液(SDD)中的释放和渗透,并研究支持ITZ-HPMCAS相互作用的分子,这些相互作用可区分级性能。
方法
对ITZ或其SDD进行了溶液稳定性评估,一维质子核磁共振(NMR)光谱,饱和转移差NMR研究,小体积溶解,固态转化研究以及体外溶解/渗透通量研究。
结果
HPMCAS-L是整体性能最好的等级,并且表现出最大的ITZ过饱和浓度,小体积溶解度和体外溶解/渗透通量。同时,在溶液稳定性研究中,H级最大程度地抑制了ITZ沉淀,而在NMR研究中,H级与ITZ表现出更大的疏水相互作用。然而,通过药物-聚合物之间的疏水相互作用获得的H级的明显优势似乎限制了SDD的总体溶解/渗透性能。
结论
体外SDD研究和药物-聚合物相互作用研究提供了对HPMCAS等级性能的了解,以及聚合物可以促进ITZ从SDD吸收的各种机理的相对贡献。