Microcrystalline diketopiperazine compositions and methods
AssigneeMannKind Corporation
InventorsBryan R. Wilson, Joseph J. Guarneri, Marshall L. Grant
Life of this patent
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Abstract
Disclosed herein are DKP microcrystals made by an improved method where they do not irreversibly self-assemble into microparticles. The microcrystals can be dispersed by atomization and re-formed by spray drying into particles having spherical shell morphology. Active agents and excipients can be incorporated into the particles by spray drying a solution containing the components to be incorporated into microcrystalline diketopiperazine particles. In particular, the microcrystalline particle compositions are suitable for pulmonary drug delivery of one or more peptides, proteins, nucleic acids and/or small organic molecules.
Claims20
A method of treating a disease or disorder comprising, administering to a subject in need of treatment a crystalline diketopiperazine composition comprising a plurality of microcrystalline primary particles of about 0.4 pm in diameter having a substantially hollow spherical structure and comprising a shell comprising interlocking crystallites of the diketopiperazine that do not irreversibly self-assemble, the diketopiperazine crystallites having a specific trans isomer content of about 45% to 65%, and wherein the primary particles are disrupted then dispersed by atomization and formed into larger microcrystalline particles of about 2.4 pm in diameter by spray-drying surfactant-free solutions comprising the primary particles, wherein about 92% of the microcrystalline larger particles have a volumetric median geometric diameter less than 5.8 pm and further comprise one or more active ingredients comprising a prostaglandin, prostaglandin analog, or derivative thereof,
- wherein said crystalline diketopiperazine composition comprises a diketopiperazine of the formula:
A method of treating a disease or disorder comprising, administering to a subject in need of treatment a crystalline diketopiperazine composition comprising a plurality of microcrystalline primary particles of about 0.4 μm diameter having a substantially hollow spherical structure and comprising a shell comprising interlocking crystallites of a diketopiperazine that do not irreversibly self-assemble, the diketopiperazine crystallites having a specific trans isomer content of about 45% to 65% and wherein the primary particles are disrupted then dispersed by atomization and formed into larger microcrystalline particles by spray-drying surfactant-free solutions comprising the primary particles, and the diketopiperazine has the formula:
- wherein the plurality of microcrystalline particles comprise a prostaglandin or an analog thereof, and about 74% of the larger microcrystalline particles have a diameter of about 2.4 μm.
Dependencies are inferred from the claim text.