Abstract: A method of co-formulating two or more pharmaceutically active compounds into a particulate product including contacting a dense, supercritical or near-critical fluid With a suspension of a first active compound in a medium that is miscible with the dense fluid and a solution of a second active compound in a solvent that is miscible with the dense fluid. The product may be the first active agent coated with the second active agent. The method may use coaxial nozzles for the fluid, media or solvents. The method may be applied to production of dry powders for inhalation including beta-agonists and corticosteroids. Apparatus for use in the method comprising means for streams of solvents, media and dense fluids to enter a precipitation chamber at substantially the same point and means for collection of particles under gravity in one or more collection chambers.

Abstract: Provided herein are novel neuromodulatory compounds and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein. In other embodiments, provided herein are methods of agonizing dopaminergic D2 receptors and/or antagonizing or inhibiting activity of receptors such as the 5-HT2 receptors using the compounds and compositions disclosed herein.

Abstract: Provided herein are novel iso-ergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1Breceptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2Breceptors using the compounds and compositions disclosed herein.

Abstract: Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: A new particle morphology of glucocorticosteroids is described. The forms have a particle morphology that is particularly well suited for use in an inhaled corticosteroid drug suspension formulation for delivery from a next generation nebulizer device. Use of the new glucocorticosteroid particles enables enhanced drug delivery efficiency and increased residence time of the delivered drug in the lungs. New methods for producing glucocorticosteroid particles having these specific particle morphologies are also described. The methods provide a simplified, reproducible and scalable particle formation process that can produce glucocorticosteroid particles having a narrow particle size and shape distribution, a low surface energy, a low aspect ratio, uniform particle morphology and a reduced specific surface area.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: The invention provides an apparatus for forming fine particles of a substance in a precipitation chamber, in which the apparatus has means to convey the fine particles from the precipitation chamber to at least one particle collection chamber, downstream of the precipitation chamber, the particle collection chamber having an inlet and an outlet separate from the inlet. The invention also provides a method of forming fine particles of a substance, the method comprising contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a collection chamber, the collection chamber having an inlet and an outlet separate from the inlet.

Abstract: Described here are compositions and methods for the treatment of respiratory conditions using glucocorticosteroids delivered by a next generation nebulizer. The methods administer a therapeutic dose with nebulization time of 2 minutes or less. The faster nebulization time improves patient compliance.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: The present invention provides for an enhanced eductor element that significantly increases the amount of pressure generated at the siphon tube without significantly increasing the flow resistance through the eductor. The invention further provides for breath-actuated inhalation devices comprising the enhanced eductor element as an actuation mechanism.

Abstract: Provided herein are novel ergoline derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and or 5-HT1B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein.

Abstract: The invention provides a method for manipulating or formulating a solid substance which melts under pressure of a gas without degrading at a temperature lower than the melting point of the substance at atmospheric pressure including: applying to the substance a liquefied gas or dense gas to melt the substance without degrading the substance; then contacting the molten substance with a carrier fluid, which is at substantially the same pressure as the liquefied gas or dense gas, to form a solution or mixture of at least a part of the molten substance and the carrier fluid; and passing the solution or mixture into a vessel of lower pressure than the pressure of the liquefied gas or dense gas and carrier fluid to form particles of the substance; and particles formed by the method.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: The present disclosure describe inhalation particles where each discrete unagglomerated inhalation particle comprising 2 or more active pharmaceutical ingredients. In one embodiment, the inhalation particles comprise a first and a second API where the second API covers, at least partially, and protects the first API from degradation or instability. Inhalation particles comprising a first and a second API as described herein have many advantages over present means of delivering two or more APIs. Formulations comprising such inhalation particles are also described.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Abstract: The invention provides an apparatus for forming fine particles of a substance in a precipitation chamber, in which the apparatus has means to convey the fine particles from the precipitation chamber to at least one particle collection chamber, downstream of the precipitation chamber, the particle collection chamber having an inlet and an outlet separate from the inlet. The invention also provides a method of forming fine particles of a substance, the method comprising contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a collection chamber, the collection chamber having an inlet and an outlet separate from the inlet.

Abstract: Pharmaceutical aerosol formulations of dihydroergotamine, or pharmaceutically acceptable salts thereof, to administer dry powders and propellant suspensions via pulmonary aerosol or nasal spray inhalation. Such formulations may be used for the treatment of various disease states and conditions, including, but not limited to, migraine headaches. The dihydroergotamine particles are produced using a supercritical fluid process. The aerosol formulations disclosed have superior stability, purity and comprise particle of respirable size particularly suitable for pulmonary delivery.