Thermo-kinetic mixing for pharmaceutical applications

Inventors

Brough, Chris • McGinity, James W. • Miller, Dave A. • DiNunzio, James C. • Williams, III, Robert O.

Assignees

The University of Texas System • AustinPx LLC

Abstract

Compositions and methods for making a pharmaceutical dosage form include making a pharmaceutical composition that includes one or more active pharmaceutical ingredients (API) with one or more pharmaceutically acceptable excipients by thermokinetic compounding into a composite. Compositions and methods of preprocessing a composite comprising one or more APIs with one or more excipients include thermokinetic compounding, comprising thermokinetic processing the APIs with the excipients into a composite, wherein the composite can be further processed 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.

Core Innovation

A method of making a composite processes one or more active pharmaceutical ingredients having an immiscible crystalline or intermediate morphology with one or more pharmaceutically acceptable excipients by thermokinetic compounding. The processing renders the API amorphous, and the amorphous character improves the miscibility of the API and the excipients and the dissolution rate of the composite as compared to thermally processing the crystalline or intermediate morphology API with the excipients by a process other than thermokinetic compounding.

Thermokinetic compounding in an enclosed thermokinetic chamber thermokinetically processes APIs with pharmaceutically acceptable excipients to form amorphous composites, including amorphous character and heterogeneously homogeneous composites, and in some cases a single-phase amorphous composite. The resulting composite structure supports improved miscibility between API and excipient and improved dissolution rate of the composite.

The described approach supports conversion of an API from an immiscible crystalline or intermediate morphology into an amorphous form, including single-phase amorphous material, and enables enhanced dissolution rate and supersaturation behavior in drug-excipient composites. It is further described as enabling nanocomposites and nanoconfinement and as allowing tuning of drug release when formulated as dosage forms.

Claims Coverage

The document includes one independent claim defining the thermokinetic-compounding method, with multiple dependent claims refining the method and composite characteristics. The inventive coverage centers on transforming APIs with an immiscible crystalline or intermediate morphology into an amorphous API within a composite by thermokinetic compounding and comparing dissolution and miscibility outcomes versus non-thermokinetic thermal processing.

Overall, the claim coverage focuses on converting immiscible crystalline or intermediate morphology APIs to amorphous form via thermokinetic compounding to improve miscibility and dissolution rate versus non-thermokinetic thermal processing, with refinements including potency retention, exclusion of a processing agent, single-phase amorphous composite, particular cellulose-derivative excipient options, and optional release-profile formulation types.

Stated Advantages

Documented Applications