Patent ID: 7468428
Filing Date: 2008-12-23
Classification: A61K,Y02A

Abstract:
1. A method of producing a stable, sterile pharmaceutical formulation comprising lyophilized azithromycin, which method comprises: (a) preparing a liquid composition comprising an ethanolate of azithromycin, an acid selected from the group consisting of citric acid, hydrochloric acid, lactic acid, glycolic acid, acetic acid, phosphoric acid, and tartaric acid, and an aqueous solvent, (b) chilling the composition to a temperature from about −10° C. to about 15° C., wherein the temperature is maintained for at least about 20 minutes to about 2 hours, (c) freezing the composition to a temperature of from about −30° C. to about −50° C., to produce a frozen mixture, wherein the temperature is maintained for at least about 1 hour, (d) subjecting the frozen mixture to a primary drying stage, which comprises applying a vacuum to reduce the pressure by an amount effective to remove aqueous solvent from the frozen mixture, and, while applying the vacuum, changing the temperature of the frozen mixture to a primary drying temperature, wherein the primary drying temperature is from about 0° C. to about 20° C., and wherein the primary drying temperature is maintained for at least about 20 hours to about 40 hours, to produce a first intermediate, and (e) subjecting the first intermediate to a secondary drying stage, which comprises applying a vacuum to reduce the pressure by an amount effective to remove aqueous solvent from the first intermediate, and, while applying the vacuum, (i) changing the temperature of the first intermediate to a first secondary drying temperature, wherein the first secondary drying temperature is from about 20° C. to about 40° C., and wherein the first secondary drying temperature is maintained for at least about 10 hours to about 20 hours, and (ii) changing the temperature of the first intermediate to a second secondary drying temperature, wherein the second secondary drying temperature is from about 30° C. to about 50° C., and wherein the second secondary drying temperature is maintained for at least about 10 hours to about 20 hours, to produce the pharmaceutical formulation, wherein ethanol is present in an amount from about 0.005% to about 0.5% by weight of the pharmaceutical formulation.