Considerations and Challenges to Develop Drug-drug Coamorphous System: A Recent Update

Poor water solubility of several drugs, especially BCS class II and IV drugs, restricts their dissolution and negatively affects oral absorption. Amorphization of drugs is a year-old approach to enhance solubility and dissolution of poorly water-soluble drugs. Polymeric amorphous systems have been proven effective but have disadvantages, such as low drug loading, high carrier content, etc. In a coamorphous system, a small molecule can be used as a coformer that keeps the amorphous form of a drug stable. In a drug-drug coamorphous system (CAS), one therapeutically active moiety can act as a coformer for the other drug. Although effective, the rationale of selecting the drugs and optimising the ratio without compromising therapeutic effect and safety is challenging. The preparation method is also a challenge because the stress during the processing method may result in the loss of crystallinity. Hence, the processing stability of the amorphous drug is a significant concern. A stable CAS is formed when two drugs generate some molecular-level interaction. In silico prediction of miscibility, molecular dynamic simulation, functional group analysis by Fourier Transform infrared spectroscopy, Raman spectroscopy, NMR, etc. contribute to the analysis of molecular-level interaction. Additionally, the article discusses the preparation method and the selection of excipient to form an effective CAS.