Beta-hairpin peptidomimetic with elastase inhibitory activity and aerosol dosage forms thereof

A kit for the preparation and delivery of a pharmaceutical aerosol for pulmonary administration comprising a dispersed liquid phase and a continuous gas phase;

• wherein the dispersed liquid phase
• (a) comprises aqueous droplets comprising the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-);
• or pharmaceutically acceptable salt thereof;
• wherein
• OctG is (S)-2-aminodecanoic acid;
• DPro is D-proline;
• (b) has a mass median diameter from about 1.5 μm to about 5 μm;
• and
• (c) has a droplet size distribution having a geometrical standard deviation from about 1.2 to about 1.7;
• and wherein the kit comprises a nebulizer and a liquid composition comprising a concentration within a range from about 4 mg/mL to about 100 mg/mL of the active compound;
• or pharmaceutically acceptable salt thereof, having a dynamic viscosity in the range from about 0.8 mPas to about 1.7 mPas and a surface tension in the range from about 25 mN/m to 80 mN/m;
• or
• wherein the dispersed liquid phase
• (a) comprises aqueous droplets comprising the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-);
• or pharmaceutically acceptable salt thereof;
• wherein
• OctG is (S)-2-aminodecanoic acid;
• DPro is D-proline;
• (b) has a mass median diameter from about 1.5 μm to about 5 μm;
• and
• (c) has a droplet size distribution having a geometrical standard deviation from about 1.2 to about 1.7;
• and
• wherein the kit comprises a nebulizer and a solid pharmaceutical composition for preparing the liquid composition, wherein the solid composition comprises the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-);
• or pharmaceutically acceptable salt thereof;
• and wherein the solid composition is dissolvable or dispersible in an aqueous liquid solvent, and wherein the liquid composition comprises a concentration within a range from about 4 mg/mL to about 100 mg/mL of the active compound;
• or pharmaceutically acceptable salt thereof, having a dynamic viscosity in the range from about 0.8 mPas to about 1.7 mPas and a surface tension in the range from about 25 mN/m to 80 mN/m.

A method of preparing and delivering an aerosol for pulmonary administration, said method comprising the steps of

• (a) providing a liquid pharmaceutical composition comprising the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-);
• or pharmaceutically acceptable salt thereof;
• in a concentration within a range from about 4 mg/mL to about 100 mg/mL;
• or providing a solid pharmaceutical composition for preparing the liquid composition, wherein the composition comprises the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-);
• or pharmaceutically acceptable salt thereof;
• and wherein the solid composition is dissolvable or dispersible in an aqueous liquid solvent, and wherein the liquid composition comprises a concentration within a range from about 4 mg/mL to about 100 mg/mL of the active compound;
• or pharmaceutically acceptable salt thereof, having a dynamic viscosity in the range from about 0.8 mPas to about 1.7 mPas and a surface tension in the range from about 25 mN/m to 80 mN/m;
• (b) providing a nebulizer capable of aerosolizing said liquid pharmaceutical composition at a mean delivery rate of at least about 0.8 mg of the active compound cyclo(-OctG-Glu-Thr-Ala-Ser-Ile-Pro-Pro-Gln-Lys-Tyr-DPro-Pro-);
• or pharmaceutically acceptable salt thereof;
• per minute;
• the nebulizer being further adapted to emit an aerosol comprising a dispersed liquid phase having a mass median diameter from about 1.5 μm to about 5 μm;
• and having a droplet size distribution having a geometrical standard deviation from about 1.2 to about 1.7;
• and
• (c) operating the nebulizer to aerosolize the liquid pharmaceutical composition.