Claims for Patent: 12,409,180

Summary for Patent: 12,409,180

Title:	Formulation production process
Abstract:	The present invention relates to a process for producing a sterile liquid pharmaceutical composition suitable for administration by inhalation comprising ensifentrine particles, wherein the process comprises: (a) heating ensifentrine particles at a temperature of from 100° C. to 220° C. to obtain sterile ensifentrine particles; and (b) combining the sterile ensifentrine particles with a sterile liquid vehicle to produce the sterile liquid pharmaceutical composition suitable for administration by inhalation. A process for producing an ampule comprising the sterile liquid pharmaceutical composition is also described.
Inventor(s):	Peter Lionel Spargo, Phillip A. Haywood, Edward James French
Assignee:	Verona Pharma PLC
Application Number:	US18/946,234
Patent Claims:	1. A sterile liquid pharmaceutical composition comprising sterile ensifentrine particles suitable for administration by inhalation, wherein the composition is produced by a method comprising: (a) dry heating ensifentrine particles as a dry powder at a temperature of from 145° C. to 175° C. for 45 minutes to 160 minutes to obtain the sterile ensifentrine particles, and (b) combining the sterile ensifentrine particles with a sterile liquid vehicle to produce the sterile liquid pharmaceutical composition suitable for administration by inhalation; wherein the dry heating produces less than a 0.5% w/w increase in total impurities. 2. The composition of claim 1, wherein the dry heating is performed at a temperature of 155° C. to 165° C. for 110 minutes to 130 minutes. 3. The composition of claim 1, wherein the sterile ensifentrine particles comprise at least 95% by weight of ensifentrine or a pharmaceutically acceptable salt thereof relative to a total weight of the sterile ensifentrine particles. 4. The composition of claim 1, wherein the sterile ensifentrine particles comprise at least 95% by weight of ensifentrine free base relative to a total weight of the sterile ensifentrine particles. 5. The composition of claim 1, wherein the sterile ensifentrine particles have a particle size distribution with a Dv10 of from 0.1 μm to 1.0 μm. 6. The composition of claim 1, wherein the sterile ensifentrine particles have a particle size distribution with a Dv50 of from 0.5 μm to 5.0 μm. 7. The composition of claim 1, wherein the sterile ensifentrine particles have a particle size distribution with a Dv90 of from 2.5 μm to 6 μm. 8. The composition of claim 1, wherein the method further comprises subjecting a liquid vehicle to aseptic filtration to produce the sterile liquid vehicle. 9. The composition of claim 1, wherein the sterile liquid vehicle comprises a diluent and optionally one or more additional excipients selected from surfactants, buffers, and tonicity adjusters. 10. The composition of claim 9 comprising (a) sterile ensifentrine particles at a concentration of from 0.5 mg/mL to 6 mg/ml; (b) one or more surfactants at a concentration of from 0.01 mg/mL to 2 mg/ml; (c) a buffer at a concentration of from 0.6 mg/mL to 4 mg/mL; (d) a tonicity adjuster at a concentration of from 5 mg/mL to 12 mg/mL. 11. The composition of claim 10, wherein the sterile liquid vehicle comprises water, sodium chloride, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dihydrate, polysorbate 20, or sorbitan laurate. 12. The composition of claim 11, comprising (a) sterile ensifentrine particles at a concentration of from 0.5 mg/mL to 6 mg/ml; (b) polysorbate 20 at a concentration of from 0.1 mg/mL to 1.5 mg/ml; (c) sorbitan monolaurate at a concentration of from 0.01 mg/mL to 0.5 mg/ml; (d) sodium dihydrogen phosphate dihydrate at a concentration of from 0.3 mg/mL to 2 mg/mL; (e) disodium hydrogen phosphate dihydrate at a concentration of from 0.3 mg/mL to 2 mg/mL; and (f) sodium chloride at a concentration of from 5 mg/mL to 12 mg/mL, wherein a total weight of ensifentrine in the sterile liquid pharmaceutical composition is from 2.7 to 3.3 mg. 13. The composition of claim 1, wherein the sterile liquid pharmaceutical composition comprises the sterile ensifentrine particles at a concentration of from 0.1 mg/mL to 5 mg/mL. 14. The composition of claim 13, wherein the sterile liquid pharmaceutical composition comprises the sterile ensifentrine particles at a concentration of from 1 mg/mL to 2 mg/mL.