Study on redispersibility of drug nanocrystals particles during storage: Novel understanding based on water adsorption and glass transition of amorphous matrix formers.
Study on redispersibility of drug nanocrystals particles during storage: Novel understanding based on water adsorption and glass transition of amorphous matrix formers.
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DOI：
10.1016/j.ijpharm.2019.118945
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发表时间：
2019-12
影响因子：
5.8
通讯作者：
Yijing Luo;Yang Liu;Yingchong Chen;Shuyuan Shuai;Qin Zheng;Ming Yang;Pengfei Yue
中科院分区：
文献类型：
--
作者：
Yijing Luo;Yang Liu;Yingchong Chen;Shuyuan Shuai;Qin Zheng;Ming Yang;Pengfei Yue
本研究的目的是了解药物纳米晶-聚集体(NAP)在储存过程中的吸水和玻璃化转变对NAP在水中再分散性的影响，并基于Guggenheim-Anderson-de Boer(GAB)和Gordon-Taylor模型确定NAP粉末的临界储存策略。以芹菜素为模型药物。以蔗糖(SU)、乳糖(LA)、海藻糖(TR)、菊糖(IN)、麦芽糊精(MA)和PVPK30(PV)为基质，制备了芹菜素纳米聚集态微粒(AN-NAPS)。结果表明，6种AN-NAP基质形成剂的吸附等温线均为典型的II(S)型吸附。水分活度显著影响AN-NAP的再分散性，这可能是由于在高水分活度或高水分条件下吸湿导致非晶态基质的微结构崩塌所致。MD基AN-NAP(AN-NAP/MD)在高水活度(0.689)下表现出比其他非晶态基质更好的再分散性。与其他基质形成剂相比，MD能显著增大AN-NAP体系的玻璃化转变温度，防止AN-NAP的聚集。AN-NAPs的临界水分活度和含水率分别为0.015-0.545和0.0412-0.1508微克水/克干物质。在所有基于非晶态基质的NAP中，AN-NAP/MD的临界水活度最高(0.545)，临界含水率为0.1003 g水/g干物质，其次是基于AN-NAP的TR。MD可作为纳米晶聚集颗粒在储存过程中的优良基质成形剂。基于GAB模型和Gordon-Taylor模型，成功地阐明了药物纳米粒在储存过程中的吸水性和玻璃化转变对药物纳米粒再分散性的影响，并提出了药物纳米粒再分散的临界储存策略。
The objective of this study was to understand the influence of the water adsorption and glass transition of matrix formers on redispersibility in water of drug nanocrystals-aggregated particles(NAP) during storage, and the critical storage strategy for NAP powders were determined based on the Guggenheim-Anderson-de Boer (GAB) and the Gordon-Taylor models. Apigenin was used as model drug. Six kinds of matrix formers sucrose(SU), lactose(LA), trehalose(TR), inulin(IN), maltodextrin(MA) and PVPK30(PV) were used to prepare apigenin nanocrystals-aggregated particles (AN-NAPs). The results demonstrated that the adsorption isotherms curves of six kinds of matrix formers based AN-NAPs all showed typical II (S) type adsorption. The water activity significantly influenced the redispersibility of AN-NAP, which could be attributed to the microstructure collapse of amorphous matrix induced by moisture adsorption at high water activity or high moisture. MD based AN-NAP(AN-NAP/MD) exhibited much better redispersibility at high water activity(0.689) compared with the other amorphous matrix formers. MD was able to significantly enlarge the Tg of AN-NAP system and prevent from aggregation of AN-NAP compared to other matrix formers. And the critical water activity and moisture content of AN-NAPs were in the ranges of 0.015–0.545 and 0.0412–0.1508 g water/g dry matter, respectively. Of all amorphous matrix based NAPs, the critical water activity of AN-NAP/MD was the highest (0.545), and the critical moisture content was 0.1003 g water/g dry matter, and followed by TR based on AN-NAP. MD could be used as an excellent matrix former for nanocrystals-aggregated particles during storage. Therefore, the roles of water adsorption and glass transition of matrix formers on redispersibility of drug nanocrystals-aggregated particles during storage was successful elucidated, and the critical storage strategy was proposed based on the GAB model and the Gordon-Taylor model.