Differential Scanning Calorimetry (DSC) in the Study of Potential Incompatibilitis Between Fluconazole and Selected Pharmaceutical Excipients: Różnicowa kalorymetria skaningowa DSC w badaniu potencjalnych niezgodności pomiędzy flukonazolem a wybranymi substancjami pomocniczymi

Abstract

Studies of interactions between active pharmaceutical ingredients (APIs) and pharmaceutical excipients are one of the key aspects of quality control in the drug manufacturing. Potential physical and/or chemical incompatibilities may affect its stability, bioavailability, and consequently, the pharmacotherapeutic efficacy and safety. The aim of this work was to show the application of the differential scanning calorimetry (DSC) method in the assessment of the possible influence of selected pharmaceutical excipients on the physical properties of fluconazole. Therefore, a set of mixtures of fluconazole with microcrystalline cellulose Vivapur 12 and 112, Vitacel M80 cellulose, Maltodextrin N, corn starch - Starch 1500, agglomerated α-lactose Tabletoza, β-cyclodextrin and xylitol were examined. The measurements were carried out using both raw materials and physical mixtures in mass ratios of 1:9, 3:7, 1:1, 7:3, 9:1. In order to show the possible influence of manufacturing processes (such as milling, wet milling, granulation, compression etc.), micronized (kneaded) and co-precipitated (from water/alcohol solutions) mixtures were prepared and examined in a 1:1 weight ratio. The analysis of the DSC curves consisted in comparing the values of the maximum temperature Tmax, as well as the shape, height and area under the endothermic peaks of the melting process.

The main reason for writing this publication was the lack of easily available scripts or books in polish, concerning the subject of thermal analysis - especially differential scanning calorimetry DSC. By submitting this scientific and didactic article, we hope it would be a useful tool and teaching aids for students of pharmacy faculties and medicinal colleges.