Processing-Induced Phase Transformations and Their Implications on Pharmaceutical Product Quality

Selection of the physical form of the active pharmaceutical ingredient is a careful and deliberate process since it can influence the stability and performance of the dosage form. The manufacture of solid dosage forms entails several unit operations which are a source of processing stresses. There is also potential for interaction of drug with excipients. Pharmaceutical processing steps can provide an avenue to intentionally alter and control the physical form of the API (and excipients) and thereby achieve the critical product attributes. On the other hand, processing-induced transformations may be inadvertent and detrimental to product quality. Formulation and process development strategies should be aimed at reproducibly controlling the desired physical form. A QbD approach to product development should include control of material properties and process parameters to support these strategies based on a thorough understanding of such transformations.