The Roles of Vitrification of Stabilizers/Matrix Formers for the Redispersibility of Drug Nanocrystals After...

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 (T _g) 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 T _g 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 T _g were very important for preserving the stability of drug nanocrystals during storage.