Multiple speed process for preserving heat sensitive portions of a thermokinetically melt blended batch

摘要

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.

主权项

1. A method of melt-blending a composition of two or more ingredients comprising one or more crystalline, thermolabile active pharmaceutical ingredients (API's) and one or more pharmaceutically acceptable excipients or carriers, wherein a thermokinetic compounding of the ingredients takes place when the ingredients are heated by way of being processed at high rotational speeds of shaft extensions on a motor driven shaft in a mixing chamber of a thermokinetic mixer, whereby the resulting composition forms a melt blended pharmaceutical composition with a substantially higher amorphosity and reduced crystallinity of the API's than in the original ingredients, the method additionally comprising operating the motor driven shaft for a first time period at a first lower speed until achieving a predetermined parameter, at which time the shaft speed is adjusted to a second higher speed for a second time period, wherein the mixing process is uninterrupted between the first and second time periods.