The present disclosure is directed to compositions and methods for making a pharmaceutical composition by thermokinetic compounding, wherein the compositions include one or more thermolabile components, for example one or more active pharmaceutical ingredients (API) with one or more pharmaceutically acceptable excipients. The methods comprise thermokinetic processing of the thermolabile components into a composite by blending certain thermolabile components in a thermokinetic mixer using multiple speeds during a single, rotationally continuous operation. The composite can be further processed into pharmaceutical compositions by conventional methods known in the art, such as hot melt extrusion, melt granulation, compression molding, tablet compression, capsule filling, film-coating, or injection molding.