The Roles of Vitrification of Stabilizers/Matrix Formers for the Redispersibility of Drug Nanocrystals After Solidification: a Case Study
The Roles of Vitrification of Stabilizers/Matrix Formers for the Redispersibility of Drug Nanocrystals After Solidification: a Case Study
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稳定剂/基质形成剂的玻璃化对药物纳米晶体固化后的再分散性的作用：案例研究
DOI：
10.1208/s12249-015-0461-3
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发表时间：
2016-12
影响因子：
3.3
通讯作者：
Wang Yaqi
中科院分区：
文献类型：
--
作者：
Yue Pengfei;Xiao Mingsheng;Xie Yuanbiao;Ma Yueqin;Guan Yongmei;Wu Zhenfeng;Hu Pengyi;Wang Yaqi
为了阐明稳定剂/基质形成剂的玻璃化对药物纳米晶粉末在储存应力下固化后的再分散性的影响，系统研究了不同干燥方法和储存应力对药物纳米晶稳定性的影响。以难溶药物黄芩苷为模型药物，制备了黄芩苷纳米晶(BCN-NC)。在两种不同的应力条件下，BCN-NC的残余水分含量分别被定义为“保守”(<；1%)和“侵略性”(>；1%)。系统研究了不同稳定剂、基质形成剂和储存应力对BCN-NC粉末再分散性的影响。结果表明，储存应力对BCN-NC的再分散性有显著影响。由于玻璃化导致BCN-NC团聚加剧，侵蚀性储存温度和残留水分可能是影响药物纳米晶稳定性的不利因素。结果表明，喷雾干燥BCN-NC的玻璃化过程依赖于温度和时间。与吐温80、d-α生育酚聚乙二醇1000琥珀酸酯或RH40相比，具有较高玻璃化转变温度的聚合物稳定剂羟丙甲基纤维素和羧甲基淀粉钠在保护BCN-NC储存过程中起到更重要的保护作用。此外，高Tg的聚乙烯吡咯烷酮K30(PVP K30)和乳糖是保持BCN-NC再分散性的有效基质形成剂。结果表明，稳定剂/基质形成剂的玻璃化转变可能是药物纳米晶在储存过程中聚集的原因，这是一个与时间相关的过程。适当的残留水分(RMC)和玻璃化转变温度(Tg)对药物纳米晶在储存过程中的稳定性非常重要。
To elucidate the roles of vitrification of stabilizers/matrix formers for the redispersibility of drug nanocrystal powder after solidification at storage stress, the influence of different drying methods and storage stresses on stability of drug nanocrystals was systemically investigated. A poorly soluble drug, baicalin, used as model drug was converted into baicalin nanocrystals (BCN-NC). The residual moisture contents of BCN-NC were applied at two different stress conditions defined as “conservative” (<1%) and “aggressive” (>1%), respectively. The influence of different stabilizers, matrix formers, and storage stresses on the redispersibility of BCN-NC powder was systemically investigated, respectively. The results showed that storage stresses had significantly influence the redispersibility of BCN-NC. Aggressive storage temperature and residual moisture could be unfavorable factors for stability of drug nanocrystals, due to the exacerbation of aggregation of BCN-NC induced by vitrification. It was demonstrated that vitrification of spray-dried BCN-NC was dependent on temperature and time. The polymeric stabilizers hydroxypropylmethylcellulose (HPMC) and sodium carboxymethyl starch (CMS-Na) with high glass transition temperature (Tg) played more important role in protecting the BCN-NC from breakage during storage, compared to the surfactants Tween 80, d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS), or RH 40. Besides, the polyvinylpyrrolidone K30 (PVP K30) and lactose with high Tg were effective matrix formers for preserving the redispersibility of BCN-NC. It was concluded that the vitrification transition of stabilizers/matrix formers could be responsible for aggregation of drug nanocrystals during storage, which was a time-dependent process. The suitable residual moisture contents (RMC) and Tg were very important for preserving the stability of drug nanocrystals during storage.
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影响因子：
2.9
作者：
A. Shrestha;Tharalinee Ua-arak;B. Adhikari;T. Howes;B. Bhandari
通讯作者：
A. Shrestha;Tharalinee Ua-arak;B. Adhikari;T. Howes;B. Bhandari
影响因子：
5.8
作者：
Pengfei Yue;Changhong Wang;Jixiu Dan;Wei Liu;Zhenfeng Wu;Ming Yang
通讯作者：
Pengfei Yue;Changhong Wang;Jixiu Dan;Wei Liu;Zhenfeng Wu;Ming Yang
影响因子：
5.8
作者：
Kumar, Sumit;Gokhale, Rajeev;Burgess, Diane J.
通讯作者：
Burgess, Diane J.
DOI：
10.1016/j.ifset.2005.05.003
发表时间：
2005-12-01
影响因子：
6.6
作者：
Cano-Chauca, M;Stringheta, PC;Cal-Vidal, J
通讯作者：
Cal-Vidal, J
DOI：
10.1081/jfp-200060262
发表时间：
2005-05
期刊：
--
影响因子：
--
作者：
A. M. Righetto;F. Netto
通讯作者：
A. M. Righetto;F. Netto