title: Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation.
abstract: The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied.
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi , Mississippi , MS , USA .
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.forename: Xingyou
authors.initials: X
authors.lastname: Ye
authors.forename: Jun-Bom
authors.initials: JB
authors.lastname: Park
authors.forename: Wenli
authors.initials: W
authors.lastname: Lu
authors.forename: Joe
authors.initials: J
authors.lastname: Morott
authors.forename: Brad
authors.initials: B
authors.lastname: Beissner
authors.forename: Zhuoyang John
authors.initials: ZJ
authors.lastname: Lian
authors.forename: Elanor
authors.initials: E
authors.lastname: Pinto
authors.forename: Vivian
authors.initials: V
authors.lastname: Bi
authors.forename: Stu
authors.initials: S
authors.lastname: Porter
authors.forename: Tom
authors.initials: T
authors.lastname: Durig
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D011345:Fenofibrate / Q000008:administration & dosage* / Q000737:chemistry; D006358:Hot Temperature; D006813:Humidity; D007700:Kinetics; D008956:Models, Chemical; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
chemical_list: D011108:Polymers; D002482:Cellulose; C008079:hydroxypropylcellulose; D011345:Fenofibrate
keywords: Avrami equation; hot-melt extrusion; kinetics model; physical stability; recrystallization