The co-amorphous solid dispersion system is one of the methods to improve the physicochemical characteristics and stability of a drug. With the appropriate material ratio and preparation method, a co-amorphous solid dispersion system can increase the bioavailability of the drug due to an increase in solubility. In addition, the co-amorphous system will maintain its amorphous shape longer than a single compound. However, using unsuitable materials and methods for co-amorphous fabrication will precipitate them and diminish their bioavailability. As a result, exploring the fundamentals of co-amorphous manufacturing methods is essential. This article discusses the physicochemical properties and solubility of co-amorphous mixtures prepared by solvent evaporation, milling, and quenching methods. Scopus, PubMed, and Google Scholar literature were obtained using the keywords 'co-amorphous preparation', 'co-amorphous method', 'solvent evaporation for co-amorphous preparation', 'milling methods for co-amorphous preparation', and 'quenching method for co-amorphous preparation'. We excluded literature whose application was not in the medical field. Based on the findings, the co-amorphous preparation methods have their respective advantages and disadvantages. Solvent evaporation can only be used on a small scale. Milling techniques are laborious and time-consuming but have a large yield and less chemical destruction, while the quenching method is only intended for thermostable compounds.

Semisolid preparations are widely used to deliver drugs through the skin, cornea, rectal tissue, nasal mucosa, vagina, buccal tissue, urethral membrane, and outer ear lining. They can prevent the first-pass metabolism, reduce side effects, provide immediate local effects, and increase patient compliance. However, an improper manufacturing process will produce a system with bad characteristics, one of which is the mixing process. Several conditions that need to be considered, such as vacuum, temperature, humidity, pressure, stirring speed, stirring time, shear stress, the volume of the mixture, and type of impeller, can affect the consistency, size, and dispersion of particle size, homogeneity, porosity, reactivity, and other characteristics that affect the quality of the semisolid system. Therefore, this article discusses the critical aspects of semisolid mixing, the types, principles, and specifications of several mixer tools and impellers, and how they affect the characteristics of semisolid systems. This review concludes that each type of semisolid preparation requires an impeller and mixer with the specifications and mixing conditions that suit the needs in maintaining the stability and quality of the semisolid system.