Particulate materials
View Patent ↗Embodiments of the invention relate to particles of active substances, methods for preparing the particles, formulations containing the particles, and metered dose inhalers containing such particles or formulations. In one embodiment, a composition of an aerosol formulation is provided and contains a particulate active substance of non-micronized, solid particles having a mass median aerodynamic diameter of less than 10 μm suspended in a hydrofluorocarbon fluid vehicle at a concentration within a range from about 0.2% w/v to about 5% w/v. The aerosol formulation exhibits a flocculation volume of about 85% or greater about 1 minute after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle. The particulate active substance contains an alkaloid ergotamine, pharmaceutically acceptable salts thereof, analogs thereof, or derivatives thereof. In some examples, the alkaloid ergotamine contains dihydroergotamine, such as dihydroergotamine mesylate and the hydrofluorocarbon fluid vehicle contains HFA 134a, HFA 227ea, or mixtures thereof.
1. A composition of an aerosol formulation, comprising:
a particulate active substance of non-micronized, solid particles having a mass median aerodynamic diameter of less than 10 μm, suspended in a hydrofluorocarbon fluid vehicle at a concentration within a range from about 0.2% w/v to about 5% w/v, wherein the aerosol formulation exhibits a flocculation volume of about 85% or greater about 1 minute after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle, and the particulate active substance is a drug for use in the treatment of migraine.
2. The composition of claim 1 , wherein the hydrofluorocarbon fluid vehicle comprises 1, 1, 1, 2-tetrafluoroethane (HFA 134a), 1, 1, 1, 2, 3, 3, 3-heptafluoropropane (HFA 227ea), or mixtures thereof.
3. The composition of claim 1 , wherein the aerosol formulation exhibits a flocculation volume of about 85% or greater about 5 minutes after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle.
4. The composition of claim 3 , wherein the aerosol formulation exhibits a flocculation volume of about 85% or greater about 10 minutes after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle.
5. The composition of claim 4 , wherein the aerosol formulation exhibits a flocculation volume of about 100% about 10 minutes after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle.
6. The composition of claim 1 , wherein the particulate active substance is suspended in the hydrofluorocarbon fluid vehicle at a concentration within a range from about 0.2% w/v to about 3% w/v.
7. The composition of claim 6 , wherein the particulate active substance is suspended in the hydrofluorocarbon fluid vehicle at a concentration within a range from about 0.5% w/v to about 1.5% w/v.
8. The composition of claim 1 , wherein the mass median aerodynamic diameter is about 5 μm or less.
9. The composition of claim 8 , wherein the mass median aerodynamic diameter is about 3 μm or less.
10. The composition of claim 1 , wherein the particulate active substance is in a crystalline form.
11. The composition of claim 10 , wherein the crystalline form is significantly longer in one dimension than in at least one other dimension.
12. A composition of an aerosol formulation, comprising: a particulate active substance of non-micronized, solid particles having a mass median diameter of less than 15 μm, suspended in a hydrofluorocarbon fluid vehicle at a concentration within a range from about 0.2% w/v to about 5% w/v, wherein the aerosol formulation exhibits a flocculation volume of about 85% or greater about 1 minute after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle, and the particulate active substance is a drug for use in the treatment of migraine.
13. The composition of claim 12 , wherein the hydrofluorocarbon fluid vehicle comprises 1, 1, 1, 2-tetrafluoroethane (HFA 134a), 1, 1, 1, 2, 3, 3, 3-heptafluoropropane (HFA 227ea), or mixtures thereof.
14. The composition of claim 13 , wherein the mass median diameter is about 3 μm or less.
15. The composition of claim 12 , wherein the aerosol formulation exhibits a flocculation volume of about 85% or greater about 10 minutes after mixing the particulate active substance and the hydrofluorocarbon fluid vehicle.
16. The composition of claim 12 , wherein the particulate active substance is suspended in the hydrofluorocarbon fluid vehicle at a concentration within a range from about 0.2% w/v to about 3% w/v.