Liquid inhalation formulation comprising RPL554
The present invention relates to a liquid pharmaceutical composition suitable for administration by inhalation which comprises a diluent and a suspension of particles of 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable salt thereof. Also described is a liquid pharmaceutical composition according to the invention for use in the treatment of the human or animal body.
1. A liquid pharmaceutical composition suitable for administration by inhalation comprising a diluent and a suspension of particles of 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable salt thereof,
wherein the composition comprises a phosphate buffer at a concentration of less than about 5 mg/mL;
wherein the particles of RPL554 have a particle size distribution with a Dv50 (median particle size by volume) value of from about 0.2 μm to about 5 μm,
wherein the concentration of particles of RPL554 in the liquid pharmaceutical composition is from about 0.1 mg/mL to about 6 mg/mL.
2. A liquid pharmaceutical composition according to claim 1 , wherein the composition does not comprise a phosphate buffer.
3. A liquid pharmaceutical composition according to claim 2 , wherein the composition does not comprise a buffer.
4. A liquid pharmaceutical composition according to claim 1 , wherein the particles of RPL554 have a particle size distribution with a Dv50 value of from about 0.7 μm to about 2.5 μm.
5. A liquid pharmaceutical composition according to claim 1 , wherein the composition further comprises one or more surfactants.
6. A liquid pharmaceutical composition according to claim 5 , wherein the one or more surfactants are selected from one or more non-ionic surfactants.
7. A liquid pharmaceutical composition according to claim 5 , wherein the one or more surfactants are selected from polyoxyethylene glycol sorbitan alkyl esters and sorbitan alkyl esters.
8. A liquid pharmaceutical composition according to claim 1 , wherein the composition further comprises a tonicity adjuster.
9. A liquid pharmaceutical composition according to claim 1 , wherein the tonicity adjuster is sodium chloride.
10. A liquid pharmaceutical composition according to claim 1 , wherein the diluent is water.
11. A liquid pharmaceutical composition according to claim 1 , wherein composition is suitable for administration by nebulizer.
12. A nebulizer comprising a composition according to claim 1 .