DSC kinetic study of the incompatibility of doxepin with dextrose Application to pharmaceutical preformulation studies Faranak Ghaderi 1,2 • Mahboob Nemati 1,3 • Mohammad R. Siahi-Shadbad 1,4 • Hadi Valizadeh 5 • Farnaz Monajjemzadeh 1,4 Received: 10 January 2015 / Accepted: 17 August 2015 Ó Akade ´miai Kiado ´, Budapest, Hungary 2015 Abstract In the present paper, the physicochemical incompatibility of doxepin with dextrose was evaluated in solid-state mixtures. The compatibility was evaluated using different physicochemical methods such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy and mass spectrometry. Non-isothermally stressed physical mixtures were used to study the solid- state kinetic parameters. Different thermal models such as Friedman, Flynn–Wall–Ozawa and Kissinger–Akahira– Sunose were used for the characterization of the drug– excipient mixtures. Overall, the incompatibility of doxepin as a tertiary amine with dextrose as a reducing carbohy- drate was successfully assessed. DSC-based kinetic anal- ysis is a simple and fast method in evaluation of different drug–excipient mixtures incompatibility. Finally, it can be recommended to exclude dextrose from doxepin pharma- ceutical formulations and also to apply the easy and ver- satile DSC method in kinetic study of drug–excipient incompatibility. Keywords Doxepin  Dextrose  Incompatibility  Kinetic  DSC  Mass Introduction Thermal methods have been widely used for the assess- ment of possible interactions between formulation com- ponents of pharmaceutical preparations since 1970. Thermal analysis is a group of techniques in which a property of the tested material is measured versus time or temperature, whereas the sample is heated or cooled at a constant rate of temperature variations or kept at fixed temperature [1]. These techniques give valuable infor- mation about drug and excipient interaction, which might cause significant changes in the chemical properties, stability, solubility, absorption and therapeutic response of drugs [2, 3]. Application of DSC has been suggested as a fast method for evaluating the physiochemical interaction between formulation components [4–7]. Mul- tiple scan method at different heating rates using iso- conversional calculation procedures is an alternative to the conventional method, in order to calculate solid-state kinetic parameters. Friedman (FR), Kissinger–Akahira– Sunose (KAS) and Flynn–Wall–Ozawa (FWO) methods have been widely used to study the kinetic parameters [8–10]. Fourier transform infrared (FTIR) spectroscopy is a simple, rapid and precise technique for the evaluation of the drug–excipient incompatibility. Any change in position or intensity, disappearance and appearance of an absorption band in IR spectra can refer to drug–excipient interactions [11, 12]. Doxepin hydrochloride is a dibenzoxepin-derivative tricyclic antidepressant (TCA). TCAs contain a tricyclic & Farnaz Monajjemzadeh Monajjemzadehf@yahoo.com; Monaggemzadeh@tbzmed.ac.ir 1 Department of Pharmaceutical and Food Control, Tabriz University of Medical Sciences, Tabriz, Iran 2 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 3 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 4 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 5 Department of Pharmaceutics, Tabriz University of Medical Sciences, Tabriz, Iran 123 J Therm Anal Calorim DOI 10.1007/s10973-015-4995-0