Amorphous efavirenz and the production thereof

Abstract

Efavirenz compositions of enhanced bioavailability are described that contain efavirenz with at least one solubility-enhancing polymer. Described methods to produce the bioenhanced products comprise solvent spray drying. One aspect of the method includes the steps of providing a mixture comprising efavirenz, a solubility-enhancing polymer and a single solvent, a solvent blend or solvent / non-solvent blend removing and then evaporating the mixture to form amorphous efavirenz.

Description

REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Pat. App. No. 60 / 703,374, filed Jul. 28, 2005, the contents of which are hereby incorporated by reference.BACKGROUND OF THE INVENTION [0002] The present invention is directed to compositions containing amorphous efavirenz and methods for producing amorphous efavirenz. More particularly, the present invention relates to compositions and methods for preparing amorphous efavirenz utilizing at least one solubility-enhancing polymer. In accordance with one embodiment, the efavirenz is dissolved in a solvent containing the polymer. In yet another embodiment, a blend of solvent / non-solvent for the polymer is employed. The amorphous efavirenz product can be produced by any method suitable to the composition. When necessary, solvent can be removed from compositions to yield the amorphous efavirenz product. In one further development of the invention, efavirenz-polymer-solvent (or a solvent / non-solvent blend) ...

AI Technical Summary

Benefits of technology

[0010] The use of a solvent / non-solvent blend system has been found to provide additional benefits beyond the benefits obtained with a solvent only system. This solvent / non-solvent approach can produce a spray dried powder of lower residual solvent content and smaller particle size. A further consequence of this engineered particle morphology is the increase in bulk powder density. Increased powder density is an important attribute for many applications. The extent of polymer collapse—and therefore the net effect on the spray dried powder properties—depends on the polymer solvation factors, such as the initial ratio of solvent to non-solvent, the polymer chemical structure and the polymer molecular weight. In addition to reducing residual solvent content and increasing density, the primary polymer may be paired with the solvent / non-solvent system in order to affect not only the morphology of the particle, but also that of the efavirenz, and thereby affect the efavirenz loading, crystallinity, solubility, stability and release.

[0011] The presence of additional polymers may contribute to the final particle morphology by their interaction with the first polymer and the solvent system. These additional polymers may also be advantageous to create special release properties of the active. For example, the primary polymer may be paired with the solvent / non-solvent system in order to affect particle morphology, and thereby residual solvent content and bulk powder density. Additional polymeric adjuvants may be added to serve additional purposes: further inhibit active recrystallization, further maximize active concentration, and further enhance / delay / retard dissolution rate. To accomplish these functionalities, it is necessary to suitably match the adjuvant solubilities with the solvent blend selected for the primary polymer.

Problems solved by technology

Eventually, the solvent composition is insufficient to maintain the polymer in solution.

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