Mechanisms Of Solid State And Solution Instability Of Drugs

Abstract

The physical stability of pharmaceutical formulations is a critical aspect of drug development and commercialization. Solid-state reactions, including phase transformations and chemical reactivity, can significantly impact the stability and performance of drug products. This review examines the importance of solid-state properties and their relationship to the developability of drug candidates. The paper discusses analytical techniques for characterizing amorphous dispersions, the role of amorphous molecular mobility, drug-excipient interactions, and the impact of solid-state reactions on drug stability and solubility.  Practical strategies for the evaluation and development of stable solid dispersions are proposed, including the use of a working diagram to assess drug-polymer solubility and miscibility.  By understanding the complex mechanisms of solid-state and solution instability, including factors such as environmental influences and molecular interactions, researchers can optimize the design, development, and formulation of drug products to improve their overall developability and commercial viability. The acceptable physical stability of drug formulations is a fundamental requirement for the successful development, manufacturing, and commercialization of pharmaceutical products. This includes ensuring that the medications maintain their potency and effectiveness over time, as well as remain chemically stable under various storage conditions. The increasing application of enabling delivery techniques, such as amorphous dispersions and other advanced formulations, poses even greater challenges to the physical stability of pharmaceutical products. Ensuring the stability of drug formulations is crucial for their successful development, manufacturing, and commercialization.  The development and commercialization of[1] pharmaceutical products require a thorough understanding of the mechanisms underlying the solid-state and solution instability of drugs. This review paper aims to provide a comprehensive overview of the key factors and analytical techniques involved in the physical stability of pharmaceutical formulations, with a focus on amorphous dispersions. Amorphous solid dispersions, which are one of the most promising areas in the pharmaceutical field, have become increasingly important in the development of new drug products. However, the inherent thermodynamic instability of amorphous systems poses significant challenges in maintaining their physical stability during manufacturing, storage, and in vivo drug release (Vasconcelos et al., 2016).