title: The Roles of Vitrification of Stabilizers/Matrix Formers for the Redispersibility of Drug Nanocrystals After Solidification: a Case Study.
abstract: 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 Tgwere 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 Tgwere very important for preserving the stability of drug nanocrystals during storage.
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China. ypfpharm@126.com.
authors.forename: PengFei
authors.initials: P
authors.lastname: Yue
authors.affiliation: 94th Hospital of People's Liberation Army, Nanchang, China.
authors.forename: MingSheng
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: YuanBiao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.|94th Hospital of People's Liberation Army, Nanchang, China.
authors.forename: YueQin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: YongMei
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: ZhenFeng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: PengYi
authors.initials: P
authors.lastname: Hu
authors.affiliation: Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: YaQi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry*; D065347:Hypromellose Derivatives / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013213:Starch / Q000031:analogs & derivatives / Q000737:chemistry; D013696:Temperature; D058989:Vitrification; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D005079:Excipients; D005419:Flavonoids; D011108:Polymers; D011208:Powders; C038044:baicalin; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D013213:Starch; C034848:carboxymethyl starch; D011205:Povidone; D024502:alpha-Tocopherol
keywords: baicalin; nanocrystals; redispersibility; storage stress; vitrification