Methods and compositions for treating pulmonary hypertension
AssigneeMannKind Corporation
InventorsJohn J. Freeman, Marshall L. Grant, Jason J. Antunovich, William Elliott Bay
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Abstract
Inhalable compositions for treating pulmonary hypertension comprising treprostinil, derivative thereof or analogs thereof and a method for treating pulmonary arterial hypertension and/or idiopathic pulmonary fibrosis are disclosed herein. Methods of manufacturing pharmaceutical compositions are also disclosed. Compositions are based on diketopiperazine powders for pulmonary inhalation.
Claims17
A process for making an inhalable dry powder composition comprising,
- preparing a suspension of microcrystalline particles of (E)-3,6-bis[4-(N-carbonyl 2-propenyl)amidobutyl]-2,5-diketopiperazine in an aqueous ammonia solution and combining an acetic acid solution in a high shear mixer at a temperature ranging from 13° C. to about 20° C. while mixing in a high shear mixer to form a suspension;
- washing the suspension in water;
- pelletizing the suspension in a cryogranulator, and drying the suspension in a lyophilizer to collect the microcrystalline particles of the diketopiperazine;
- resuspending the microcrystalline particles of the diketopiperazine in in a solution of deionized water and ethanol;
- preparing a hydrophobic compound in in a solution of about 70% to about 100% ethanol, and adding the solution to the suspension with mixing and drying the suspension.
An inhaler comprising a hydrophobic compound made by the process comprising,
- preparing a suspension of microcrystalline particles of (E)-3,6-bis[4-(N-carbonyl 2-propenyl)amidobutyl]-2,5-diketopiperazine in an aqueous ammonia solution and combining an acetic acid solution in a high shear mixer at a temperature ranging from 13° C. to about 20° C. while mixing in a high shear mixer to form a suspension;
- washing the suspension in water;
- pelletizing the suspension in a cryogranulator, and drying the suspension in a lyophilizer to collect the microcrystalline particles of the diketopiperazine;
- resuspending the microcrystalline particles of the diketopiperazine in in a solution of deionized water and ethanol;
- preparing the hydrophobic compound in in a solution of about 70% to about 100% ethanol, and adding the solution to the suspension with mixing and drying the suspension.
A method of treating pulmonary hypertension comprising administering to a patient in need of treatment an inhalable, substantially crystalline dry powder composition comprising a treprostinil dose in an amount of up to 200 μg and one or more pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and/or excipient, wherein said administering comprises at least one to four inhalations per day.
Dependencies are inferred from the claim text.