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

Abstract

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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is related to and claims priority under U.S. Provisional Application Ser. No. 60 / 957,044, filed on Aug. 21, 2007, U.S. Provisional Application No. 61 / 050,922, filed on May 6, 2008, application Ser. No. 12 / 196,154, filed on Aug. 21, 2008, and International Patent Application 20 PCT / US2008 / 073913, entitled “Thermo-Kinetic Mixing for Pharmaceutical Applications,” filed on Aug. 21, 2008, and is a continuation of U.S. patent application Ser. No. 13 / 190,176 filed Jul. 25, 2011 entitled “Multiple Speed Process for Preserving Heat Sensitive Portions of a Thermokinetically Melt Blended Batch”, the entire contents of each of which are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Field of the Invention[0003]The present disclosure relates in general to the field of pharmaceutical manufacturing, and more particularly, to thermokinetic mixing of active pharmaceutical ingredients (APIs) to produce novel dosage forms...

AI Technical Summary

Benefits of technology

The present disclosure is about a new thermokinetic mixer and mixing process that can blend heat sensitive or thermolabile components without excessive heat input or degradation. This is useful for processing mixtures that include thermolabile components who can degrade if exposed to high temperatures. The mixer uses multiple speeds during a single, rotationally continuous operation on a batch containing thermolabile components, and the resulting pharmaceutical compositions have increased bioavailability and stability. The mixer can be easily scaled to commercial production of pharmaceutical compositions. The invention provides a method for controlling the shear delivered to a particle, which in turn provides control over shaft energy translated into heat energy available for softening or melting a polymer part of a particle in a thermokinetic mixing chamber. The mixer is designed to maintain a hygroscopic condition or maximize shear during batch processing.

Problems solved by technology

Current high-throughput molecular screening methods used by the pharmaceutical industry have resulted in a vast increase in the proportion of newly discovered molecular entities which are poorly water-soluble.

The therapeutic potential of many of these molecules is often not fully realized either because the molecule is abandoned during development due to poor pharmacokinetic profiles, or because of suboptimal product performance.

Also, in recent years the pharmaceutical industry has begun to rely more heavily on formulational methods for improving drug solubility owing to practical limitations of salt formation and chemical modifications of neutral or weakly acidic / basic drugs.

Although the application of thermokinetic compounding in the field of pharmaceutical manufacturing offers significant advantages over other methodologies known in the pharmaceutical arts, it is possible that issues can arise in continuously melt blending certain heat sensitive or thermolabile components with certain non-thermolabile components using a thermokinetic mixer.

In certain cases, this results in an exceedance of a limit temperature or heat input for an unacceptable duration.

The batch thus experiences unacceptable degradation of the thermolabile components, as the substantial amount of heat absorbed by the entire batch results in thermal degradation of thermolabile components instead of increasing overall batch temperature.

Substantially complete amorphosity is a measure well-known in the art of pharmaceutical preparation and processing; bioavailability may be significantly impaired in compositions lacking substantially complete amorphosity.

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