CHAPTER 1. Preformulation Studies

Abstract

At various stages during development, it is essential to understand the physicochemical characteristics of compounds or biological entities that can affect their development into final products. Data acquired from such preformulation studies forms an important basis for understanding the potential pharmacokinetics of a drug in humans and animals and the opportunities and limitations for process change as the product is scaled up in manufacture. Preformulation studies are also performed to predict the stability of the formulation during manufacture, transport and storage and thus determine the shelf life of the marketed product. The chapter covers the measurement of solubility and dissolution rate, molecular dissociation, pKa, diffusion, partition and permeability; and how these can be included in a biopharmaceutical classification system. Moisture uptake and sorption; the classification of hygroscopicity and evaluation of polymorphism and crystallinity is outlined together with methodology, such as differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and powder X-ray diffraction. Assessing the stability of active ingredients and excipients, both in isolation and in combination, is covered using stress testing, including the effect of pH, temperature, humidity, light and oxidizing agents. Finally, reference is made to the characterisation of powders and particulate systems by measuring their fundamental and derived properties.