Evaluation of The Inter-Batch Variability of An Active Pharmaceutical Ingredient: Morphologic, Rheologic And Calorimetric Characterization

Abstract

All raw materials used for solid oral drugs manufacturing must be evaluated according to the pharmacopoeial monographs, which consist in a verification of critical quality attributes related to the identity and purity of the molecule. However, active pharmaceutical ingredients may present differences in non-pharmacopoeial tests, such as particle size and shape or flow. Although these differences are not evaluated routinely by Quality Control area, they can alter the technological performance during production, as well the stability and ultimately the efficacy of a pharmaceutical product. In this study, 10 production batches of magnesium valproate were evaluated, characterizing flow index, fusion enthalpy and particle shape and size distribution. An analysis of variance was carried out, finding statistically-significant differences in the flow index, particle shape and fusion enthalpy tests for two batches. These differences may be due to small variations in the crystalline configurations. The study showed differences in the characterization of fundamental and functional properties of the particles of the active pharmaceutical ingredient evaluated, which could have an impact on the manufacturing processes and affect therapeutic efficacy.