Dry powder compositions for intranasal delivery
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Publication Number
US-11331270-B2
Publication Date
2022-05-17
Expiration Date
Abstract
The present application relates to a pharmaceutical composition in a form of dry powder for intranasal administration, comprising solid particles of at least one active agent and solid particles of a diluent, said pharmaceutical composition being substantially free of excipients other than the solid diluent, wherein said pharmaceutical composition having at least 90% of the particles of said at least one active agent with a mean particle size of 10-30 microns and less than 10% of the particles of said at least one active agent with a mean particle size equal to or below 5 microns. The particles of said diluent have a mean particle size of 30-200 microns. The present application also relates to an apparatus and modified spray drying method for preparation of the pharmaceutical composition of the present invention in the dry powder form.
Core Innovation
The invention relates to a pharmaceutical composition in a form of dry powder for intranasal administration to a patient in need thereof. The dry powder includes solid particles consisting of at least one active agent and solid particles of a disaggregation agent. The active-agent particle size distribution is defined such that at least 90% of the solid particles of the active agent have a mean particle size ranging from 10 microns to 30 microns, and less than 10% of the solid particles have a mean particle size equal to or below 5 microns.
A key aspect of the invention is combining the active-agent particles with solid disaggregation-agent particles to reduce aggregation and support intranasal delivery. The composition is described as substantially free of other excipients, and targeting is directed to the uppermost region of the nasal cavity. The disaggregation agent is provided as solid particles, with examples including lactose monohydrate and lactose functional analogues.
The document further describes an apparatus and dry-powder preparation workflow using spray-drying and particle separation/collection equipment. The workflow includes a spray-drying chamber, cyclone separator with vortex separation, bag filtration, and a receiving chamber that is pre-filled with diluent or disaggregation-agent particles for continuous in-situ blending with stirring/homogenising.
Claims Coverage
The independent claim covers a dry-powder intranasal pharmaceutical composition defined by two inventive features: a specific active-agent particle-size distribution and the presence of solid disaggregation-agent particles. Dependent claims further refine disaggregation-agent particle sizes, materials, anatomical targeting, and preparation apparatus/workflow.
Dry-powder composition for intranasal administration
A pharmaceutical composition in a form of dry powder for intranasal administration to a patient in need thereof, consisting of solid particles consisting of at least one active agent and solid particles of a disaggregation agent.
Active-agent particle-size distribution limits
At least 90% of the solid particles of the at least one active agent have a mean particle size ranging from 10 microns to 30 microns, and less than 10% of the solid particles of the at least one active agent have a mean particle size equal to or below 5 microns.
Uppermost nasal-region targeting for transmucosal systemic administration
Intranasal administration to target the uppermost region of the nasal cavity to achieve transmucosal systemic administration.
Disaggregation-agent particle-size range
The disaggregation-agent solid particles have a mean particle size of 50-150 microns.
Lactose functional analogue disaggregation agent
The disaggregation agent is the lactose functional analogue selected from cellulose and derivatives, starch and derivatives, dextrose, sorbitol, mannitol, maltitol, xylitol, or mixtures thereof.
Spray-drying, cyclone separator/vortex separation, bag filtration, and in-chamber continuous blending
Preparing and collecting active-agent particles using a spray-drying chamber, cyclone separator using vortex separation with bag filtration, and a receiving chamber pre-filled with solid particles of a disaggregation agent for mechanical stirring/homogenising to combine the active-agent particles with the disaggregation agent.
Overall, the claims focus on a dry-powder intranasal composition defined by a tightly specified active-agent particle-size distribution combined with solid disaggregation-agent particles, with dependent claims further specifying disaggregation-agent types and particle sizes, anatomical targeting to the uppermost nasal region for transmucosal systemic administration, and a preparation workflow using spray-drying with cyclone/vortex separation, bag filtration, and in-chamber continuous blending.
Stated Advantages
Improved intranasal pharmacokinetics compared with an oral solution for oxycodone, including faster T_max and higher brain/plasma exposure.
Reported comparative in vivo advantages for intranasal powder versus oral solution for oxycodone, including plasma and brain exposure outcomes.
Documented Applications
Intranasal administration to a patient in need thereof, including targeting of the uppermost region of the nasal cavity to achieve nose-to-brain and/or transmucosal systemic administration.
Comparative delivery of oxycodone via intranasal powder versus oral solution, evaluated using rat brain and plasma pharmacokinetics.
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