Dry powder compositions for intranasal delivery
Inventors
TEMTSIN-KRAYZ, Galia • Megiddo, Dalia • Lapidot, Tair • Abrutzky, Carolina
Assignees
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Publication Number
US-11202757-B2
Publication Date
2021-12-21
Expiration Date
Abstract
A pharmaceutical composition in a form of dry powder for intranasal administration includes solid particles of at least one opioid receptor antagonist as active ingredient and two types of solid particles. A naloxone pharmaceutical composition in the form of dry powder for intranasal administration, including as active agent naloxone or a pharmaceutically acceptable salt thereof. A kit for intranasal administration of naloxone. A method of treating opioid overdose/intoxication and/or a symptom thereof in a patient in need thereof by intranasally administering a therapeutically effective amount of a composition including solid particles of at least one opioid receptor antagonist as active ingredient and two types of solid particles.
Core Innovation
The invention relates to a pharmaceutical composition in a form of dry powder for intranasal administration that includes a first type of solid particles and a second type of solid particles. The first type particles consist of at least one opioid receptor antagonist as the active ingredient, while the second type particles comprise a pharmaceutically acceptable disaggregating agent. The composition is defined by controlled particle-size distributions between the two particle types, including that at least 90% of the first type particles have a mean particle size of about 10 to about 30 microns, and less than about 10% are at or below about 10 microns.
The second type particles have a mean particle size greater than that of the first type particles, and the formulation uses substantially excipient-free compositions where a solid diluent prevents aggregation. The particle engineering supports targeted nasal deposition by providing a major deposition in the nasal turbinates region and the olfactory region, while limiting deposition to the lungs to less than about 1%.
A further aspect is the delivery as a disposable intranasal dose unit that provides a therapeutically effective metered dose of the opioid receptor antagonist. For the naloxone embodiment, the composition includes first type particles with naloxone or a pharmaceutically acceptable salt thereof and second type particles comprising lactose monohydrate as a disaggregation agent, while maintaining the specified particle-size constraints between the two particle types.
Claims Coverage
The independent claims are directed to two inventive features: a dry-powder intranasal opioid receptor antagonist composition with two particle populations having defined mean particle-size distributions, and a specific naloxone embodiment using lactose monohydrate as the disaggregation agent with a metered therapeutically effective nominal dose.
Two particle types with engineered particle-size distribution
A pharmaceutical composition in a form of dry powder for intranasal administration, comprising a first type of solid particles and a second type of solid particles, wherein the first type particles consist of at least one opioid receptor antagonist as active ingredient, and the second type of solid particles comprise a pharmaceutically acceptable disaggregating agent, wherein at least 90% of said first type particles are of a mean particle size of about 10 to about 30 microns, and less than about 10% of said first type particles are of a mean particle size equal to or below about 10 microns and said second type particles are of a mean particle size greater than that of said first type particles.
Naloxone plus lactose monohydrate disaggregation agent with controlled particle sizes
A naloxone pharmaceutical composition in the form of dry powder for intranasal administration, comprising a first type of solid particles and a second type of solid particles, wherein the first type particles consist of naloxone or a pharmaceutically acceptable salt thereof as active agent, and the second type of solid particles comprise lactose monohydrate as disaggregation agent, wherein at least about 90% of said first type particles are of a mean particle size of about 10 to 30 microns and less than about 10% of said first type particles are of a mean particle size equal to or below about 10 microns and said second type particles are of a mean particle size greater than that of said first type particles, providing a metered therapeutically effective nominal dose of said naloxone or pharmaceutically acceptable salt thereof.
The independent claim coverage is centered on engineered two-population dry-powder intranasal formulations in which an opioid receptor antagonist, including naloxone in the specific embodiment, is placed in a first particle population with a defined mean particle-size range and a limited low-end fraction, while a second particle population containing a disaggregating agent has a higher mean particle size; the naloxone embodiment further specifies lactose monohydrate as the disaggregation agent and a metered therapeutically effective nominal dose.
Stated Advantages
Provides major nasal deposition in turbinates/olfactory region while limiting deposition to the lungs to less than about 1%.
Supports treatment of opioid overdose or intoxication via intranasal administration with a dry powder formulation.
Prevents aggregation and supports substantially excipient-free compositions through use of a solid diluent/disaggregating agent.
Enables dose-device uniformity and relative exposure comparisons versus NARCAN® nasal spray.
Improves stability and performance, including amorphous retention and nasal cast deposition characteristics.
Documented Applications
Intranasal treatment of opioid overdose or intoxication using a dry-powder opioid receptor antagonist formulation, including naloxone.
Nasal deposition targeting, including deposition to the nasal turbinates region and olfactory region with lung deposition limited to less than about 1%.
Use as a kit including disposable intranasal dose units for opioid overdose treatment.
Performance evaluation including nasal cast deposition study and pharmacokinetic comparisons versus NARCAN® nasal spray.
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