title: Effects of Temperature and Solvent on the Solid-State Transformations of Pranlukast During Mechanical Milling.
abstract: Four solid forms of pranlukast (PRS) were obtained during mechanical milling including neat milling (NM) and solvent-drop milling (SDM), which were characterized by various analytical techniques. The effect of milling conditions including 3 milling temperatures and 6 assist solvents on the solid-state transformations of commercial PRS (PRS HH) was systemically investigated. Milling temperature significantly influenced the NM process. A low milling temperature (5°C) led to a complete amorphization of PRS HH, whereas higher milling temperatures (15°C and 30°C) only induced a partial amorphization. The milling at 5°C was proven to be a progressive amorphization process, and the amorphous material showed an increasing stability with prolonged milling time. Amorphous PRS can stay stable under low temperature and relative humidity conditions and showed significantly higher solubilities and faster dissolution rates in both water and pH 6.8 phosphate buffer solution. A total of 6 solvents were used in the SDM experiments. N,N-dimethylformamide and dimethyl sulfoxide should be avoided in the manufacturing process of PRS because corresponding solvates of PRS can be easily generated by SDM of PRS HH with short milling time and small amount of solvents.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Xinnuo
authors.initials: X
authors.lastname: Xiong
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Du
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zeng
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D018927:Anti-Asthmatic Agents / Q000737:chemistry*; D002867:Chromones / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013696:Temperature
chemical_list: D018927:Anti-Asthmatic Agents; D002867:Chromones; D012997:Solvents; C047681:pranlukast
keywords: amorphous; crystal defects; dissolution rate; milling; solid state; solubility