Abstract: Embodiments of the invention relate to particles of active substances, methods for preparing the particles, formulations containing the particles, and metered dose inhalers containing the particles or formulations. In one embodiment, an inhaler contains an aerosol formulation containing a particulate active substance of non-micronized, solid particles having a mass median aerodynamic diameter of less than 10 ?m. The particles may be suspended in a nonsolvent hydrofluorocarbon fluid vehicle (e.g., HFA 134a or 227ea) at a concentration within a range from about 0.2% w/v to about 5% w/v. The formulation exhibits a flocculation volume of about 85% or greater about 1 minute after mixing the particulate active substance and the vehicle. The particulate active substance may contain salmeterol xinafoate, budesonide, salbutamol sulfate, dihydroergotamine mesylate, risperidone-(9-hydroxy)-palmitate, bromocriptine mesylate, or derivatives thereof. In some examples, the active substance is dihydroergotamine mesylate.

Abstract: The invention provides a method for forming particles of a target substance, comprising (a) co-introducing into a particle formation vessel, under controlled temperature and pressure, a supercritical or near-critical anti-solvent fluid; a first target substance in a first vehicle; and a second target substance in a second vehicle; and (b) using the anti-solvent to disperse the target substances in their respective vehicles and to extract the vehicles, substantially simultaneously and substantially immediately on introduction of the fluids into the particle formation vessel. The second vehicle is immiscible with the first, and contact between the first and second vehicles occurs a sufficiently short period of time before their dispersion by the anti-solvent, and with sufficient physical mixing, as to allow only insignificant, if any, phase separation to occur between the two vehicles between their contact with one another and their dispersion.

Abstract: Preparation of particles of an active substance having a layer of an additive at the particle surfaces, by dissolving both the active substance and the additive in a vehicle to form a target solution, and contacting the target solution with an anti-solvent fluid using a SEDS™ particle formation process, to cause the active substance and additive to coprecipitate. The additive is typically a protective additive, in particular a taste and/or odour masking agent. Also provided is a particulate coformulation made by the method, which has a finite gradient in the relative additive concentration, which concentration increases radially outwards from the active-rich core to the additive-rich surface of the particles.