title: Polymorphic form of piroxicam influences the performance of amorphous material prepared by ball-milling.
abstract: The objective of this study was to investigate the influence of the starting solid state form of piroxicam (anhydrate form I: PRXAH I vs form II: PRXAH II) on the properties of the resulting amorphous material. The second objective was to obtain further insight into the impact of critical factors like thermal stress, dissolution medium and storage conditions on the thermal behavior, solid state transformations and physical stability of amorphous materials. For analysis differential scanning calorimetry (DSC), Raman spectroscopy and X-ray powder diffractometry (XRPD) were used. Pair-wise distribution function (PDF) analysis of the XRPD data was performed. PDF analysis indicated that the recrystallization behavior of amorphous samples was influenced by the amount of residual order in the samples. The recrystallization behavior of amorphous samples prepared from PRXAH I showed similarity to the starting material, whereas the recrystallization behavior of amorphous samples prepared from PRXAH II resembled to that of the PRX form III (PRXAH III). Multivariate data analysis (MVDA) helped to identify that the influence of storage time and temperature was more pronounced in the case of amorphous PRX prepared from PRXAH I. Furthermore, the wet slurry experiments with amorphous materials revealed the recrystallization of amorphous material as PRXMH in the biorelevant medium.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. kn@farma.ku.dk
authors.forename: Kaisa
authors.initials: K
authors.lastname: Naelapää
authors.forename: Johan Peter
authors.initials: JP
authors.lastname: Boetker
authors.forename: Peep
authors.initials: P
authors.lastname: Veski
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Karin
authors.initials: K
authors.lastname: Kogermann
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D015999:Multivariate Analysis; D010894:Piroxicam / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam