title: Investigation of recrystallization of amorphous trehalose through hot-humidity stage X-ray powder diffraction.
abstract: The aim of this work was an investigation of the physical changes of the amorphous model material spray-dried trehalose through the use of various analytical techniques and to identify a suitable, rapid method able to quantify the changes. The crystallinity changes and recrystallization process of amorphous samples were investigated by hot-humidity stage X-ray powder diffractometry (HH-XRPD) with fresh samples, conventional X-ray powder diffractometry (XRPD) used stored samples and by differential scanning calorimetry (DSC). The data from the three methods were compared and the various forms of trehalose were analysed. HH-XRPD demonstrated that the recrystallization began at 40 and 60°C up to 45% RH and at 70°C up to 30% RH into dihydrate form. At 70°C up to 60% RH the anhydrous form of trehalose appeared too. Conventional XRPD results showed, that in the 28days stored samples the dihydrate form was detected at 40°C, 50% RH. Storage at 60°C, 40% RH resulted in the appearance of the anhydrous form and at 60°C, 50% RH both polymorphic forms were detected. By carrying out the DSC measurements at different temperatures the fraction of recrystallized trehalose dihydrate was detected. The recrystallization investigated by HH-XRPD and DSC followed Avrami kinetics, the calculated rate constants of isothermal crystallization (K) were same. Both HH-XRPD and conventional XRPD was suitable for the detection of the physical changes of the amorphous model material. DSC measurements showed similar results as HH-XRPD. Primarily HH-XRPD could be suggested for prediction, because the method is fast and every changes could be studied on one sample.
authors: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary. Electronic address: laczkovo@pharm.u-szeged.hu.
authors: Orsolya
authors: O
authors: Jójárt-Laczkovich
authors: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary; Richter Gedeon Plc., Gyömrői 19-21, H-1103 Budapest, Hungary.
authors: Gábor
authors: G
authors: Katona
authors: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors: Zoltán
authors: Z
authors: Aigner
authors: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors: Piroska
authors: P
authors: Szabó-Révész
mesh_terms: D003460:Crystallization; D006358:Hot Temperature; D006813:Humidity; D033362:Powder Diffraction / Q000379:methods*; D014199:Trehalose / Q000032:analysis / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D014199:Trehalose
keywords: Activation energy; DSC; Hot-humidity stage XRPD; Recrystallization; Trehalose