title: Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid.
abstract: To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI-20 °C < RDI-80 °C < RDI-196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.
authors.affiliation: a Department of Pharmaceutics , the 94th Hospital of People's Liberation Army , Nanchang , China.
authors.forename: Yue-Qin
authors.initials: YQ
authors.lastname: Ma
authors.affiliation: a Department of Pharmaceutics , the 94th Hospital of People's Liberation Army , Nanchang , China.
authors.forename: Zeng-Zhu
authors.initials: ZZ
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics , the 94th Hospital of People's Liberation Army , Nanchang , China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: a Department of Pharmaceutics , the 94th Hospital of People's Liberation Army , Nanchang , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics , the 94th Hospital of People's Liberation Army , Nanchang , China.
authors.forename: Han-Yang
authors.initials: HY
authors.lastname: Xiao
authors.affiliation: a Department of Pharmaceutics , the 94th Hospital of People's Liberation Army , Nanchang , China.
authors.forename: Xian-Fei
authors.initials: XF
authors.lastname: Li
mesh_terms: D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D005615:Freezing; D005947:Glucose / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D013395:Sucrose / Q000737:chemistry; D013535:Suspensions / Q000737:chemistry*; D013696:Temperature; D014580:Ursodeoxycholic Acid / Q000737:chemistry*
chemical_list: D013535:Suspensions; D065347:Hypromellose Derivatives; D013395:Sucrose; D014580:Ursodeoxycholic Acid; D005947:Glucose
keywords: Freeze-drying; nanocrystals; solidification stress; ursodeoxycholic acid