Enalapril compositions
Inventors
Rajewski, Lian G. • Rajewski, Roger A. • Haslam, John L. • Heppert, Kathleen • Beckloff, Michael C. • Segrave, Frank • Mauro, Robert • Colabuono, Peter
Assignees
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Publication Number
US-8778366-B2
Publication Date
2014-07-15
Expiration Date
Abstract
Provided herein are stable enalapril powder compositions for oral liquid formulation. Also provided herein are methods of using enalapril oral liquid formulations for the treatment of certain diseases including hypertension, heart failure and asymptomatic left ventricular dysfunction.
Core Innovation
The invention relates to stable pharmaceutical powder compositions of enalapril that are reconstituted into homogeneous, stable oral liquid formulations. The powder consists of about 14% (w/w) enalapril or a pharmaceutically acceptable salt thereof, about 85% (w/w) mannitol, and about 1% (w/w) colloidal silicon dioxide.
Mannitol is used as a stabilizing component for enalapril and is described as reducing degradation to diketopiperazine. Colloidal silicon dioxide is described as improving blend uniformity and dissolution, supporting the formation of the homogeneous reconstituted liquid.
The reconstituted oral liquid is required to be homogenous and stable for at least 12 weeks at about 25±15°C and 60±10% relative humidity. The compositions are formulated for oral administration and include reconstitution into a homogeneous oral liquid formulation suitable for therapeutic treatment.
Claims Coverage
The provided claim set includes four independent claims covering treatment of hypertension, prehypertension, heart failure, and left ventricular dysfunction. Across the independent claims, the same pharmaceutical powder composition and the same reconstituted oral liquid homogeneity/stability requirement are central inventive elements.
Reconstituted enalapril powder for treating hypertension with homogenous, stable oral liquid
A method of treating hypertension comprising administering a therapeutically effective amount of a pharmaceutical powder reconstituted into an oral liquid formulation, wherein the powder consists of about 14% (w/w) enalapril or a pharmaceutically acceptable salt thereof, about 85% (w/w) mannitol, and about 1% (w/w) colloidal silicon dioxide, and wherein the reconstituted liquid is homogenous and stable for at least 12 weeks at about 25±15°C and 60±10% relative humidity.
Reconstituted enalapril powder for treating prehypertension with homogenous, stable oral liquid
A method of treating prehypertension comprising administering a therapeutically effective amount of a pharmaceutical powder reconstituted into an oral liquid formulation, wherein the powder consists of about 14% (w/w) enalapril or a pharmaceutically acceptable salt thereof, about 85% (w/w) mannitol, and about 1% (w/w) colloidal silicon dioxide, and wherein the reconstituted liquid is homogenous and stable for at least 12 weeks at about 25±15°C and 60±10% relative humidity.
Reconstituted enalapril powder for treating heart failure with homogenous, stable oral liquid
A method of treating heart failure comprising administering a therapeutically effective amount of a pharmaceutical powder reconstituted into an oral liquid formulation, wherein the powder consists of about 14% (w/w) enalapril or a pharmaceutically acceptable salt thereof, about 85% (w/w) mannitol, and about 1% (w/w) colloidal silicon dioxide, and wherein the reconstituted liquid is homogenous and stable for at least 12 weeks at about 25±15°C and 60±10% relative humidity.
Reconstituted enalapril powder for treating left ventricular dysfunction with homogenous, stable oral liquid
A method of treating left ventricular dysfunction comprising administering a therapeutically effective amount of a pharmaceutical powder reconstituted into an oral liquid formulation, wherein the powder consists of about 14% (w/w) enalapril or a pharmaceutically acceptable salt thereof, about 85% (w/w) mannitol, and about 1% (w/w) colloidal silicon dioxide, and wherein the reconstituted liquid is homogenous and stable for at least 12 weeks at about 25±15°C and relative humidity.
Across the independent claims, the inventive concept is administering a therapeutically effective amount of an enalapril-containing pharmaceutical powder that is reconstituted into a homogeneous oral liquid having specified stability for at least 12 weeks under defined temperature and relative humidity conditions, with the powder composition defined by fixed weight percentages of enalapril (or its salt), mannitol, and colloidal silicon dioxide.
Stated Advantages
Provides a reconstituted oral liquid that is homogeneous and stable for at least 12 weeks at about 25±15°C and 60±10% relative humidity.
Mannitol is described as stabilizing enalapril and reducing degradation to diketopiperazine.
Colloidal silicon dioxide is described as improving blend uniformity and dissolution.
Includes a clinical bioavailability study showing comparable pharmacokinetics to Vasotec® under fasted conditions and food effects under fed conditions.
Documented Applications
Treating hypertension in a subject in need by administering a therapeutically effective amount of the specified pharmaceutical powder reconstituted into an oral liquid formulation.
Treating prehypertension in a subject in need by administering the specified pharmaceutical powder reconstituted into an oral liquid formulation.
Treating heart failure in a subject in need by administering the specified pharmaceutical powder reconstituted into an oral liquid formulation.
Treating left ventricular dysfunction in a subject in need by administering the specified pharmaceutical powder reconstituted into an oral liquid formulation.
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