Prediction of excipient-excipient incompatibility: A latent threat to pharmaceutical product development

The importance of pharmaceutical excipients in the creation of any dosage form is critical. These excipients are occasionally to blame for product underperformance and dosage form deterioration. Product deterioration and underperformance could be attributed to incompatibilities between drug and excipient or sometimes excipient and excipient either due to the presence of reactive impurities in the excipients or a reaction between the functional groups present on the excipients. Although the drug and excipient incompatibilities are monitored and reported, excipient-excipient incompatibilities are overlooked due to a paucity of the literature. Pharmaceutical companies used to work in a controlled environment (compatibility tests between excipients to determine the best excipients for dosage form creation) and utilize mitigation measures to suppress any incompatibilities between excipients when necessary. These tactics take time and money to implement, and they increase the cost of developing a dosage form. However, the primary goal of this review is to highlight some of the most prevalent excipient-excipient incompatibilities that can occur during dosage form development, possible incompatibility reactions, as well as a potential method for predicting excipient-excipient incompatibilities based on structural information. The structure incompatibility relationship strategy to forecast incompatibilities between diverse excipients is an idea based on the reactivity of pharmaceutical excipients, and it might be a useful tool in reducing the time, cost, and product failures during the product development due to excipient-excipient incompatibilities.