MICROCRYSTALLINE DIKETOPIPERAZINE COMPOSITIONS AND METHODS

• Main Authors: Guarneri, Joseph J, Wilson, Bryan R, Grant, Marshall L
• Format: Patent
• Language: English
• Published: 14.11.2019
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

A method of making microcrystalline diketopiperazine particles substantially uniform in size having a hollow spherical structure and comprising a shell comprising crystallites of the diketopiperazine that do not self-assemble in suspension, wherein the particles are suitable for pulmonary administration as a dry powder comprising: a) forming diketopiperazine crystallites in a surfactant-free suspension; wherein the crystallites have a size distribution as a bimodal curve as measured by laser diffraction having a first peak of crystallites of the bimodal distribution having an average size of 0.2 pm to 0.4 pm and a second peak of crystallites having an average size of 2.1 pm to 2.4 pm b) atomizing the suspension using a spray dryer under an air or gas stream, and c) forming a dry powder comprising the microcrystalline diketopiperazine particles having hollow spheres and a having a volumetric median geometric diameter of less than equal to 5 pm WO 2014/144895 PCT/US2014/029491 FIG, A FI, I4 IMMEN[ Ia INE 048- - R 0,2 -20 0.0 0.10 1.'00 10.00 100.00 diameter (pm).