Methods of use of emulsion formulations of an NK-1 receptor antagonist
Inventors
Ottoboni, Thomas B. • Han, Han
Assignees
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Publication Number
US-12115254-B2
Publication Date
2024-10-15
Expiration Date
Abstract
Disclosed herein are novel pharmaceutical formulations of a neurokinin-1 (NK-1) receptor antagonist suitable for parenteral administration including intravenous administration. Also included are formulations including both the NK-1 receptor antagonist and dexamethasone sodium phosphate. The pharmaceutical formulations are stable oil-in-water emulsions for non-oral treatment of emesis and are particularly useful for treatment of subjects undergoing highly emetogenic cancer chemotherapy.
Core Innovation
The invention relates to stable injectable oil-in-water emulsions for intravenous and parenteral administration of NK-1 receptor antagonists. The injectable oil-in-water emulsions include an NK-1 receptor antagonist selected from aprepitant, rolapitant, netupitant, and other NK-1 receptor antagonists mentioned in the document. The emulsions may further include dexamethasone sodium phosphate for co-administration in the same injectable formulation.
The formulation comprises an oil component, an emulsifier such as a phospholipid emulsifier including lecithin, a co-surfactant, and an aqueous component. The document further describes tonicity agents and pH modifiers or buffers that can be used within the formulation system, including sucrose as a tonicity agent and sodium oleate as a pH modifier, with Tris and PBS also being mentioned.
A central aspect of the invention is achieving and maintaining acceptable emulsion droplet size and large globule limits consistent with USP <729>. The document emphasizes manufacturing approaches for producing a fine emulsion and maintaining stability, including high-speed homogenization and high-pressure homogenization, and includes sterilization approaches. The resulting emulsions are characterized for stability over storage and after freeze-thaw, with physical and chemical stability assessed using particle sizing and microscopy crystal inspection.
Claims Coverage
Not explicitly described in patent.
Not explicitly described in patent.
Stated Advantages
Provides stable injectable oil-in-water emulsions suitable for intravenous and parenteral administration of NK-1 receptor antagonists.
Emulsion droplet size and large globule limits are addressed consistent with USP <729>.
Maintains physical and chemical stability over storage and after freeze-thaw.
Supports emulsion performance assessment including release and pharmacokinetic or bioequivalence comparisons versus a reference formulation such as fosaprepitant.
Allows co-release of dexamethasone in the formulation without altering aprepitant pharmacokinetics, as stated in the document.
Documented Applications
Intravenous and parenteral injection of NK-1 receptor antagonists, including aprepitant, rolapitant, and netupitant, using stable injectable oil-in-water emulsions.
Co-administration of dexamethasone sodium phosphate together with an NK-1 receptor antagonist in the same injectable oil-in-water emulsion formulation.
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