Inhalable epinephrine formulation
Inventors
Fraser, John • Dalziel, Sean Mark • Iley, Teresa • Brazier, Jonathan • Lynch, Patrick Joseph • Fredatovich, John • Trout, Benjamin Barnaby
Assignees
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Publication Number
US-12029709-B2
Publication Date
2024-07-09
Expiration Date
Abstract
The present disclosure relates to an inhalable formulation, suitable for use in a dry powder inhaler, for the delivery of epinephrine, or a pharmaceutically acceptable salt or derivative thereof. The inhalable formulation further comprises a solid carrier and results in a stable formulation with useful physical properties for delivery to the lungs of a subject in need of epinephrine.
Core Innovation
The invention relates to a dry powder inhalable formulation for inhalation by negative pressure. The formulation consists of crystalline epinephrine bitartrate together with crystalline α-lactose monohydrate, with crystalline α-lactose monohydrate present in an amount of between about 50% w/w and about 99% w/w of the entire formulation.
The invention further specifies micronized crystalline epinephrine bitartrate with defined aerodynamic particle size characteristics. In particular, micronized crystalline epinephrine bitartrate has a Dv50 between about 1.5 µm and about 3 µm and a Dv90 between about 2 µm and about 5 µm, and the dry powder inhalable formulation is substantially unchanged after storage for 6 months at 25°C and 60% relative humidity.
The invention also characterizes the powder performance by defining a fine particle fraction greater than 30%, expressed as a percentage of the fine particle dose relative to the emitted dose. The dry powder inhalable formulation is formulated for inhalation by negative pressure, and the documented description further relates these properties to formulation stability and aerodynamic particle size distribution, including deep-lung fine particle fraction.
Claims Coverage
The independent claims cover three aspects of the invention: composition with crystalline epinephrine bitartrate and crystalline α-lactose monohydrate at a defined w/w range; particle size and storage performance of micronized epinephrine bitartrate; and fine particle fraction greater than 30% with storage stability. Across these independent claims, the core inventive features center on composition, controlled particle size, negative-pressure inhalation suitability, storage stability, and fine particle fraction constraints.
Crystalline epinephrine bitartrate with crystalline α-lactose monohydrate for negative pressure inhalation
A dry powder inhalable formulation consisting of crystalline epinephrine bitartrate and crystalline α-lactose monohydrate present at between about 50% w/w and about 99% w/w of the entire formulation, wherein the dry powder inhalable formulation is formulated for inhalation by negative pressure.
Micronized crystalline epinephrine bitartrate particle size with storage unchanged after 6 months and negative pressure inhalation
A dry powder inhalable formulation consisting of micronized crystalline epinephrine bitartrate having a Dv50 of between about 1.5 µm and about 3 µm and a Dv90 of between about 2 µm and about 5 µm; and crystalline α-lactose monohydrate present at between about 75% w/w and about 99% w/w of the entire formulation, wherein the dry powder inhalable formulation is substantially unchanged after storage for 6 months at 25°C and 60% relative humidity, and wherein the dry powder inhalable formulation is formulated for inhalation by negative pressure.
Fine particle fraction greater than 30% with 6-month stability and negative pressure inhalation
A dry powder inhalable formulation consisting of micronized crystalline epinephrine bitartrate having a Dv50 of between about 1.5 µm and about 3 µm and a Dv90 of between about 2 µm and about 5 µm; and crystalline α-lactose monohydrate present at between about 75% w/w and about 99% w/w of the entire formulation, wherein the dry powder inhalable formulation provides for a fine particle fraction, expressed as a percentage of the fine particle dose relative to the emitted dose, of greater than 30% and is stable for storage for 6 months at 25°C and 60% relative humidity, wherein the dry powder inhalable formulation is formulated for inhalation by negative pressure.
Overall, the independent claims define a negative-pressure dry powder inhalable formulation centered on crystalline epinephrine bitartrate and crystalline α-lactose monohydrate, with additional constraints on epinephrine bitartrate particle size distribution, stability after 6 months at 25°C/60% relative humidity, and fine particle fraction greater than 30%.
Stated Advantages
Stability for storage for 6 months at 25°C and 60% relative humidity.
A fine particle fraction greater than 30%, expressed as a percentage of the fine particle dose relative to the emitted dose.
The dry powder inhalable formulation is substantially unchanged after storage for 6 months at 25°C and 60% relative humidity.
Formulation suitability for inhalation by negative pressure.
Documented Applications
Treating an epinephrine-responsive disease, disorder or condition by administering the dry powder inhalable formulation by allowing the subject to inhale the dry powder.
Administering the formulation to a subject using negative pressure.
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