BIOAVAILABILITY AND POLYMORPHIC STABILITY CHALLENGES AFFECTING DRUG PRODUCT’S POTENTIAL: A CRITICAL EVALUATION AND PERTINENT SOLUTION

Clinical failure remains an ongoing challenge in pharmaceutical drug product development. Solubility and permeability therefore play a very critical role in achieving desired bioavailability and pharmacological response, which in turns affects clinical safety and efficacy significantly. The situation becomes more critical when the drug candidate exhibits polymorphism and undergoes polymorphic transformation due to its meta-stable nature. This review article outlines the available technologies, pertinent regulations, the concepts involved in the enhancement of bioavailability and polymorphic stability to overcome the clinical failures. Various available technologies for bioavailability enhancement such as salification, micronization, complexation, microemulsification, nano emulsification, cocrystal formation, and amorphous solid dispersion with their advantage and disadvantage in formulating a stable drug product containing a polymorphic and meta-stable drug substance. Thermodynamic and kinetic aspects of polymorphic transformation are discussed to understand different excipient and process-induced transformation during manufacturing and shelf life of the drug product. Selecting the right instrument from the analytical toolbox is equally important to understand the diverse nature of polymorphic transformation. This review provides state-of-the-art information available on advanced analytical tools along with their capabilities, advantages, and disadvantage with respect to physical/structural analysis of polymorphs and polymorphic transformation.