Methods of use of emulsion formulations of aprepitant
Inventors
Ottoboni, Thomas B. • Han, Han
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12290520-B2
Publication Date
2025-05-06
Expiration Date
Abstract
Disclosed herein are novel pharmaceutical formulations of aprepitant suitable for parenteral administration including intravenous administration. Also included are formulations including both aprepitant 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 a physically stable injectable emulsion comprising aprepitant in water, including egg lecithin and soybean oil. The formulation further includes a co-emulsifier that is an alcohol present at less than 10 wt/wt %, together with a tonicity modifier and a pH modifier, wherein the pH modifier is sodium oleate and the pH ranges from about 7.5 to 9.0.
The injectable emulsion is characterized by a defined ratio of egg lecithin to aprepitant between about 20:1 to 25:1, and by component content ranges including 13 wt/wt % to 20 wt/wt % egg lecithin and 9 wt/wt % to 10 wt/wt % soybean oil. The emulsion is described as physically stable, including physical stability evaluated according to USP <729> using intensity-weighted mean particle size and PFAT5.
The content addresses preventing chemotherapy-induced emesis by providing stable oil-in-water injectable (IV/parenteral) emulsion formulations of aprepitant. The document also describes chemical stability requirements, including minimal drug concentration loss, and example characterization results including mean droplet size not exceeding 4500 nm and PFAT5 not less than 0.05%.
Claims Coverage
The relevant independent claim covers a physically stable injectable oil-in-water emulsion of aprepitant with specified identities and quantitative constraints for egg lecithin, soybean oil, an alcohol co-emulsifier at less than 10 wt/wt %, a tonicity modifier, and a pH modifier defined as sodium oleate. It also requires a defined egg lecithin:aprepitant ratio, a specified pH range, and physical stability.
Physically stable injectable aprepitant emulsion with egg lecithin and soybean oil
An injectable emulsion comprising aprepitant; 13 wt/wt % to 20 wt/wt % egg lecithin; 9 wt/wt % to 10 wt/wt % soybean oil; an alcohol co-emulsifier present at less than 10 wt/wt %; a tonicity modifier; a pH modifier wherein the pH modifier is sodium oleate; and water, wherein the ratio of egg lecithin to aprepitant is between about 20:1 to 25:1, wherein the pH of the emulsion ranges from about 7.5 to 9.0, and wherein the emulsion is physically stable.
The claim coverage is centered on a physically stable injectable emulsion containing aprepitant formulated with egg lecithin, soybean oil, a low-level alcohol co-emulsifier, and sodium oleate as the pH modifier, while requiring a defined egg lecithin:aprepitant ratio and a pH of about 7.5 to 9.0.
Stated Advantages
Physical stability of the emulsion.
Chemical stability, including minimal drug concentration loss.
Higher initial aprepitant levels for the emulsion versus fosaprepitant solution.
No detrimental effect of dexamethasone phosphate on aprepitant pharmacokinetics.
Documented Applications
Preventing chemotherapy-induced emesis using stable oil-in-water injectable (IV/parenteral) emulsion formulations of aprepitant.
Interested in licensing this patent?