United States Patent:   6,020,004

Assignee:  Amgen Inc. (Thousand Oaks, CA)

Filed:  April 17, 1997

The present invention relates to improved methods of making polymeric microparticles containing a variety of active ingredients, e.g. protein drugs. In addition, the present invention relates to using the above active protein containing polymeric microparticles to prepare compositions for the sustained delivery of the therapeutics.

SUMMARY OF THE INVENTION

As fully described below, the present invention provides an improved method for preparing polymeric microparticles containing an active ingredient through unique utilization of direct lyophilization of emulsion or suspension. This improved method provides several significant advantages over the processes described in the art, including, for example, 1) ease of manufacture of the active ingredient loaded microparticles (i.e. fewer and less cumbersome steps); and 2) the provision of sustained release formulations that maintain the activity and integrity of the active ingredient during release, thus providing for controlled release of active ingredient over an extended period of time. Additionally, the processes of the present invention provide the advantages of versatility as relates to the class of polymers and/or active ingredient which may be utilized, as well as attainment of higher yields, high loading, and higher loading efficiencies.

Accordingly, one aspect of the present invention relates to a new and improved process for preparing a composition comprising an active ingredient contained within polymeric microparticles, wherein a mixture of the active ingredient and the polymer are dispersed within a continuous phase, the resulting dispersion is frozen, and the water and organic solvents removed from the dispersion by lyophilization. Importantly, the present process is more refined and simpler than those described in the art, and the activity and integrity of the active ingredient is maintained throughout the process.

The present process can be generally described as comprising the steps of: (a) preparing a polymeric solution; (b) adding an active ingredient to produce a mixture; (c) dispersing said mixture within a continuous phase to produce a dispersion; (d) adding an excipient to said dispersion; (e) freezing said dispersion to produce a frozen mixture; and (f) lyophilizing said frozen mixture to produce the desired active ingredient containing microparticles. Alternatively, step (b) can be omitted and "blank" microparticles prepared, onto which active ingredient is then loaded by suspending the blank microparticles in active ingredient solution.

A second aspect of the present invention is a pharmaceutical composition for the sustained-release of an active ingredient comprising a biologically active ingredient contained within polymeric microparticles, or, alternatively, a biologically active ingredient loaded onto the polymeric microparticles. Importantly, the sustained-release compositions of the present invention maintain the activity and integrity of the active ingredient during encapsulation and release, which helps to provide for longer periods of consistent release.

Claim 1 of 23 Claims

1. A method for making a composition comprising an active ingredient contained within polymeric microparticles, wherein a mixture of the active ingredient and the polymer are dispersed within a continuous phase, and the resulting dispersion is directly lyophilized to remove the water and organic solvents and form said microparticles.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.