Detecting the Physicochemical Transformations in Solid Drug Products Stored for Long Periods of Time-Insights into...

Since differential scanning calorimetry (DSC) is an excellent method for studying phase transformations in the solid state, the purpose of this study was to assess the suitability of DSC as a method for detecting physicochemical transformations occurring in solid drug products during storage, extending also beyond their expiration date. Based on the DSC measurements of 34 commercial drug products, they were divided into three groups characterized by the fact that the DSC curves show: (I) as dominant endothermic peaks reflecting active pharmaceutical ingredients (APIs) melting, with no additional peaks from excipients, (II) in addition to the peaks reflecting APIs melting, additional peaks related to the excipients, and (III) two peaks characteristic of lactose monohydrate dehydration and melting. Analysis of the temperature ranges and the shape of the DSC peaks showed no significant differences between the six series of measurements performed between 2011 and 2022, suggesting that physicochemical changes in drug products could not be detected during storage. Only the use of principal component analysis (PCA) made it possible to separate the DSC curves obtained during long-term storage of drug products. This allows DSC to be used to detect the first signs of deterioration, but only for drug formulations in group one. Of the drug products in groups two and three, this is only possible for 14 products. It follows that the suitability of DSC for identifying physicochemical changes in products stored for long periods of time is affected by the API content and complex composition of the tablet matrix.