Microparticle Formulations for Delivery to the Upper and Central Respiratory Tract and Methods of Manufacture
OwnerTiejun Li, Brian Thomeinventors
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Abstract
Microparticle formulations are produced by contacting an aqueous solution of a protein or other active agent with an organic solvent, a counterion and a scavenging agent, and chilling the solution. The microparticles are useful for preparing stable, uniform pharmaceuticals of predetermined defined dimensions.
Claims76
A method of making a composition comprising microparticles comprising DAS 181, the method comprising:
- a) providing a feedstock composition comprising DAS181, a counterion and an organic solvent;
- and
- b) cooling the feedstock composition to below 25° C., whereby a composition comprising microparticle comprising DAS 181 is formed.
The method of any of the forgoing claims further comprising isolating the microparticles from the composition comprising microparticles, whereby a dry powder formulation of microparticles is formed.
The method of any of the forgoing claims, wherein the wt/wt amount of DAS181 in the resulting microparticles when substantially dry is about 60% to about 75% (wt/wt).
The method of any of the forgoing claims, wherein the predetermined temperature below about 25° C. is between about 4° C. to about −65° C.
The method any of the forgoing claims, wherein the predetermined temperature below about 25° C. is between about −20° C. to about −65° C.
The method of any of the forgoing claims, wherein the predetermined temperature below about 25° C. is between about −40° C. to about −65° C.
The method of any of the forgoing claims, wherein the cooling rate is about −0.1° C./min to about −1° C./min.
The method of any of the forgoing claims, wherein cooling rate is about −0.1° C./min to about −0.8° C./min.
The method of any of the forgoing claims, wherein cooling rate is about −0.1° C./min to about −0.7° C./min, about −0.3° C./min to about −0.5° C./min, about −0.4° C./min.
The method of any of the forgoing claims, wherein the microparticles have a mass median aerodynamic diameter of between about 9 microns to about 10 microns.
The method of any of the forgoing claims, further comprising adding a scavenging agent to the feedstock composition.
The method of any of any of the forgoing claims, further comprising packaging the microparticle formulation in a container comprising between about 3 ppm to about 25 ppm aldehyde.
A composition comprising microparticles wherein the microparticles comprise about 60-70% wt/wt DAS181 (SEQ ID NO:17), 1-2% wt/wt histidine, 8-10% wt/wt histidine hydrochloride, 7-10% wt/wt trehalose, 4-8% wt/wt magnesium sulfate, 1-3% citrate, and 6-10% water.
A composition comprising microparticles, wherein the microparticles, when anhydrous, comprises about 65-75% wt/wt DAS181 (SEQ ID NO:1, SEQ ID NO:2 or a mixture thereof), 1-3% wt/wt histidine, 8-11% wt/wt histidine hydrochloride, 8-11% wt/wt trehalose, 5-8% wt/wt magnesium sulfate, and 1-3% citrate.
A composition comprising microparticles wherein the microparticles comprise about 60-80% wt/wt DAS181, 4.5-6.5% wt/wt histidine, 3.5-5.5% wt/wt histidine hydrochloride, 7-11% wt/wt trehalose, 1-4% citrate, and 6-10% water.
A composition comprising microparticles that, when anhydrous, comprise about 70-80% wt/wt DAS181, 5-7% wt/wt histidine, 4-6 wt/wt histidine hydrochloride, 9-11% wt/wt trehalose, and 1.5-3.5% citrate.
Dependencies are inferred from the claim text.