Kinetics study and Hirshfeld surface analysis for atorvastatin calcium trihydrate and furosemide system

Abstract

Atorvastatin calcium trihydrate (ATV) is used for the treatment of hyperlipidemias. The prescribed drug may be associated with an adjuvant diuretic compound such as furosemide (FUR), to treat cardiovascular disorders. This work presents the pharmaceutical development of ATV and FUR mixtures by FTIR, XRPD, and thermal analysis in a long-term study. DSC results indicate atorvastatin water loss and polymorphic furosemide conversion in the temperature range 115–160 °C, as occurs with individual drugs, so it does not attest interaction between them. These are thermal phenomena that occur at a temperature attainable during tableting technology. For this reason, the kinetic study was performed in this temperature range.The kinetics of ATV and FUR was studied by Vyazovkin isoconversional method in the times of zero and 24 months and by a neural network. Hirshfeld surface calculations are also applied. These drugs in static conditions behave as an unreactive mixture. Under heating, for 〈 = 0.3, the interaction between ATV and FUR required activation energy of ˜115 kJ mol−1 at the initial time and in 24 months, this energy increases about 10%, within the experimental error, which confirms a stable system. The ATV crystallinity decreases with heating. These results corroborate for adequate stability of the system in a combined-fixed dose.