Drug Delivery through Co-amorphous Solid Dispersions: A Comprehensive and Updated Review on Physicochemical Characteristics and Biological Potential

New chemical entities with low aqueous solubility and permeability encounter significant challenges in formulation development. Low solubility is further accompanied by slow dissolution and poor bioavailability, which in turn leads to unpredictability in terms of both bioavailability and toxicity. Therefore, a significant amount of exertion is necessary to enhance solubility, dissolution, and eventually bioavailability. Additionally, to enhance the solubility properties and amorphous stability of BCS Class II medications and ultimately increase drug bioavailability, coamorphization has emerged as a promising strategy. Co-amorphous solid dispersions (CASD) are multi-component single-phase amorphous solid dispersions comprising two or more small molecules (usually known as co-formers) that might be a combination of drug-drug or drug-excipients. The selection of appropriate co-formers is critical, and the surface properties of co-amorphous formulations must be carefully evaluated, as they influence physical and chemical stability in addition to dissolution performance. Scaling up and processing co-amorphous formulations into the final dosage forms presents challenges that need to be addressed. This review will largely concentrate on the challenges, improvements, and innovations in physicochemical properties, biological characterization, and advancements of co-amorphous systems. This review will also furnish a comprehensive explanation of both established and emerging approaches utilized in the estimation of physicochemical attributes and characterization of CASD (<i>in vitro</i> and <i>in vivo</i>). Regarding CASD's potential to improve patient outcomes and therapeutic efficacy, it has emerged as a viable approach for drug candidates posing the problems of solubility and bioavailability. This approach has also increased the physical stability of drugs.