Aqueous suspensions of ciclesonide for nebulisation
This invention relates to a method for the preparation of sterile aqueous suspensions of ciclesonide by sterilization with moist heat. The invention further relates to pharmaceutical compositions in particular to sterile aqueous suspensions of ciclesonide for administration by nebulization in the prophylaxis and/or treatment of respiratory diseases.
1. A sterile aqueous suspension of ciclesonide suitable for nebulization comprising
ciclesonide having a mean particle size of about 0.1 to 8 μm,
water,
an effective amount of at least one non-ionic isotonization agent for adjusting the osmolality of the suspension to about 225-430 mosmol/kg, wherein the non-ionic isotonizing agent is selected from the group consisting of mannitol, glycerol, glucose, and mixtures thereof,
an effective amount of suspending agent for homogenously suspending the ciclesonide in the sterile aqueous suspension, wherein the suspending agent comprises polysorbate, and
at least one non-ionic pharmaceutically acceptable excipient, wherein the at least one non-ionic pharmaceutically acceptable excipient comprises citric acid in an amount to adjust the pH-value of the sterile aqueous suspension to pH of 4 to 7,
wherein the sterile aqueous suspension does not comprise sodium chloride and hydroxypropylmethylcellulose, and
wherein the aqueous suspension is sterilized using moist heat.
2. The sterile aqueous suspension according to claim 1 , wherein the ciclesonide has a mean particle size of about 1 to 6 μm.
3. The sterile aqueous suspension according to claim 1 , wherein the ciclesonide has a mean particle size of about 2 to 4 μm.
4. The sterile aqueous suspension according to claim 1 , wherein the at least one non-ionic pharmaceutical excipient is selected from the group consisting of agents for modifying pH, chelating agents, preservatives, and mixtures thereof.
5. The sterile aqueous suspension according to claim 4 , wherein the suspension also includes an agent for modifying pH that is an organic acid selected from the group consisting of tartaric acid, lactic acid, and mixtures thereof.
6. The sterile aqueous suspension according to claim 5 , wherein the suspending agent further comprises tyloxapol, poloxamers, polyoxyethylene castor oil derivatives, or mixtures thereof.
7. The sterile aqueous suspension according to claim 1 , wherein the ciclesonide concentration is about 0.005% to 0.5% w/v.
8. The sterile aqueous suspension according to claim 6 , wherein the ciclesonide concentration is about 0.005% to 0.5% w/v.
9. The sterile aqueous suspension according to claim 1 , wherein the d90 mean particle size of the ciclesonide in the sterile aqueous suspension remains less than 12 μm after 4 weeks of storage at room temperature.
10. The sterile aqueous suspension according to claim 1 , wherein the citric acid is present in the sterile aqueous suspension in an amount to adjust the pH-value of the sterile aqueous suspension to pH of 5.
11. The sterile aqueous suspension according to claim 1 , wherein the ratio between ciclesonide to suspending agent ranges from 0.05 to 50.
12. The sterile aqueous suspension according to claim 1 , wherein the citric acid is present in an amount of up to about 0.001 mol/l in the sterile aqueous suspension.
13. The sterile aqueous suspension according to claim 1 , wherein the osmolality of the suspension ranges from 250 mosmol/kg to 350 mosmol/kg.
14. The sterile aqueous suspension according to claim 1 , wherein the aqueous suspension is sterilized using moist heat at 110° C. for 120 min.