Thermal behavior of entacapone, a catechol-O-methyltransferase inhibitor used in Parkinson’s disease

Abstract

Entacapone, a selective and reversible inhibitor of catechol-O-methyltransferase, is used in the treatment of Parkinson’s disease in combination with levodopa/carbidopa to treat the symptoms of end-of-dose “wearing-off” effect. Considering that new formulations are researched constantly, proper knowledge of the active pharmaceutical ingredients is crucial in the preformulation stages. Kinetic analysis was performed using three methods: one integral—Flynn–Wall–Ozawa method, one differential—Friedman method, and modified nonparametric kinetics method (NPK). The thermoanalytical curves were registered at five different heating rates: β = 5, 7, 10, 12, and 15 °C min−1. Analysis was conducted in the dynamic air atmosphere to highlight potential thermooxidative processes. This paper deals with the investigation of solid-state stability and compatibility of binary mixture of entacapone with various pharmaceutical excipients by two instrumental techniques, such as universal attenuated total reflection Fourier transform infrared and thermal analysis (TG/DTG/HF). The excipients used in the mixture were: mannitol, silicon dioxide, talc, sorbitol, magnesium stearate, and povidone.