Preformulation studies for atorvastatin calcium An instrumental approach Mihaela Cristea 1 • Bianca Baul 2 • Ionut ¸ Ledet ¸i 2 • Adriana Ledet ¸i 2 • Gabriela Vlase 3 • Titus Vlase 3 • Bo _ zena Karolewicz 4 • Oana S ¸ tefa ˘ nescu 1 • Anca Octavia Dragomirescu 2 • Cezara Mures ¸an 5 • Dan-Simion Cipu 5 • Dana Velimirovici 5 • Mircea S ¸ tefa ˘ nescu 1 Received: 22 November 2018 / Accepted: 4 September 2019 Ó Akade ´miai Kiado ´, Budapest, Hungary 2019 Abstract This paper deals with the study of compatibility between antihyperlipidemic agent atorvastatin calcium trihydrate (ATV) and eight pharmaceutical excipients used in the development of solid dosage forms, namely citric acid, anhydrous lactose, magnesium citrate, magnesium carbonate, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, colloidal silica and sorbitol. As investigational tools, universal attenuated total reflectance Fourier transform infrared spectroscopy and powder X-ray diffractogram patterns were used for binary mixtures of ATV with each excipient at ambient condition and then completed by subjecting the samples to thermal stress using thermal analysis (TG/DTG/HF), in non-isothermal conditions and in oxidative medium. It was shown the binary mixtures do not present interactions between ATV and excipients when stored under ambient conditions for 2 months, while under thermal stress, ATV presents interactions with sorbitol. Keywords Atorvastatin Á Compatibility study Á Excipient Á FTIR Á PXRD Á Statin Á Thermal stability Introduction Pharmaceutical dosage forms contain both pharmacologically active compounds and excipients added to aid the formulation and manufacture of the subsequent dosage form for administration to patients. The properties of the final dosage forms, such as bioavailability and stability, have essential and direct impact on the therapeutic efficacy and safety of the drug. Also, the properties are highly dependent on the excipients chosen, their concentration and interaction with both the active compound and each other. Therefore, active compound–excipient compatibility studies play a key role in accelerating drug development. No longer can excipients be regarded simply as inert or inactive ingredients. There is the need of knowledge about their physical and chemical prop- erties but also about safety, handling and regulatory status of these materials, which are essential for formulators throughout the world [1, 2]. Excipients are now known to have defined functional roles in pharmaceutical dosage forms including: modulating solubility and bioavailability of the active ingre- dient(s); enhancing stability of the active ingredient(s) in final dosage forms; helping active ingredients maintain a preferred polymorphic form or conformation; acting as antioxidants, emulsifying agents, aerosol propellants, tablet binders and tablet disintegrants; preventing aggregation or dissociation. Thus, the choice of appropriate excipients is of major importance in the formulation of a new drug [3, 4]. & Ionut ¸ Ledet ¸i ionut.ledeti@umft.ro 1 Faculty of Industrial Chemistry and Environmental Engineering, Politehnica University of Timis ¸oara, Vasile Parvan Street 6, 300223 Timis ¸oara, Romania 2 Faculty of Pharmacy, University of Medicine and Pharmacy ‘‘Victor Babes ¸’’, Eftimie Murgu Square 2, 300041 Timis ¸oara, Romania 3 Research Centre for Thermal Analysis in Environmental Problems, West University of Timisoara, Pestalozzi Street 16, 300115 Timis ¸oara, Romania 4 Department of Drug Form Technology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland 5 Faculty of Medicine, University of Medicine and Pharmacy ‘‘Victor Babes ¸’’, Eftimie Murgu Square 2, 300041 Timis ¸oara, Romania 123 Journal of Thermal Analysis and Calorimetry https://doi.org/10.1007/s10973-019-08798-1