Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients Faraat Ali 1 • Robin Kumar 1 • Puran Lal Sahu 1 • Gyanendra Nath Singh 1 Received: 29 August 2016 / Accepted: 6 March 2017 Ó Akade ´miai Kiado ´, Budapest, Hungary 2017 Abstract Roflumilast (RFL), a newly approved and highly selective phosphodiesterase 4 inhibitor for the treatment of severe chronic obstructive pulmonary disease, associated with chronic bronchitis and a history of numerous exac- erbations. The main objective of this work was to evaluate the simultaneous (TG/DSC) thermoanalytical characteri- zation and compatibility of roflumilast with the widely used excipients for solid dosage form employing differ- ential scanning calorimetry (DSC), thermogravimetric analysis (TG), optical microscopy, isothermal stress testing (IST) by HPLC and liquid chromatography–mass spec- trometer techniques with Fourier transform infrared spec- troscopy (FT-IR) as a complimentary technique to contribute in the interpretation of results. The selected excipients were pregelatinized starch (PS), magnesium stearate, croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and sodium starch glycolate (SSG). The DSC curve showed a sharp endothermic melting peak at 160.43 °C for roflumilast. On the basis of the DSC results, some interactions were found with RFL–CCS, RFL–MCC, RFL–SSG and RFL–PS. However, during IST studies less than 2% change in roflumilast content was observed in all stressed physical mixtures except RFL–SSG ( \ 14%) which showed incompatibility with roflumilast. These results would be suitable for formulation development of the film- coated tablets of roflumilast. Keywords Compatibility Á HPLC Á LC–MS Á TG Á FT-IR Á DSC Introduction COPD stands for chronic obstructive pulmonary disease, and it is a treatable and preventable disease, characterized by airflow, dyspnea and chronic bronchitis. COPD is not completely reversible. Although various experimental phosphodiesterase 4 inhibitors are under clinical develop- ment, roflumilast acts as a highly selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and has been recently approved in various countries for the treatment of severe COPD. It is administered orally and belongs to BCS (biopharmaceutics classification) class II drugs which have high permeability and low solubility [1, 2]. Roflumilast chemically is 3-(cyclopropylmethoxy)- N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)-benza- mide. It occurs as a white to off-white powder. It is practi- cally insoluble in water, heptane and hexane, sparingly soluble in ethanol and freely soluble in acetone, having a molecular formula of C 17 H 14 Cl 2 F 2 N 2 O 3 and a molecular weight of 403.21 g mol -1 [3–5]. Pharmaceutical dosage forms are made up of a combi- nation of drug or active pharmaceutical ingredients (APIs) and various excipients. Excipients are included in dosage forms to support manufacture, administration or absorption [6]. The best excipients must be able to fulfill the important functions, i.e., dose, stability and discharge of API from the formulation. Although excipients considered pharmaco- logically inert, excipients can participate, initiate and propagate in chemical or physical interactions with the API, which may compromise the efficiency of a medication [7, 8]. It is not exquisitely pure. Even for the most & Faraat Ali frhtl6@gmail.com 1 Pharmaceutical Chemistry Division, Indian Pharmacopoeia Commission, Ministry of Health and Family Welfare, Government of India, Sector-23, Rajnagar, Ghaziabad, Uttar Pradesh 201002, India 123 J Therm Anal Calorim DOI 10.1007/s10973-017-6274-8