Inhalable imatinib formulations, manufacture, and uses thereof
The invention relates to inhalable imatinib formulations, manufacture, and uses thereof.
1. A method of preparing an inhalable formulation comprising:
micronizing imatinib freebase particles having type A crystal structure, the micronized imatinib freebase particles having a mass median aerodynamic diameter in the range of about 0.5 μm to about 5 μm;
suspending the micronized imatinib freebase particles in a solution;
spray drying the suspended micronized imatinib freebase particles to prepare an inhalable formulation thereof comprising less than 5% amorphous imatinib freebase particles and less than 5% water, wherein imatinib freebase is the only active pharmaceutical ingredient in the inhalable formulation.
2. The method of claim 1 wherein one or more excipients is included in the suspending step.
3. The method of claim 2 wherein the excipient is a water soluble excipient selected from the group consisting of leucine, dileucine, trileucine, trehalose, mannitol, citrate, and acetate.
4. The method of claim 2 wherein the excipient is a water insoluble excipient selected from the group consisting of lecithin and distearylphosphatidylcholine (DSPC).
5. The method of claim 1 wherein the inhalable formulation contains a therapeutically effective amount of imatinib freebase for treating a condition of the pulmonary cardiovascular system.
6. The method of claim 5 wherein the condition of the pulmonary cardiovascular system is pulmonary arterial hypertension (PAH).
7. The method of claim 1 wherein the inhalable formulation comprises less than 1% amorphous imatinib freebase particles.
8. The method of claim 1 wherein the inhalable formulation comprises less than 1% water.