Emulsion formulations of an NK-1 receptor antagonist and uses thereof
Inventors
Ottoboni, Thomas B. • Han, Han
Assignees
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Publication Number
US-9974742-B2
Publication Date
2018-05-22
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 provides a stable injectable pharmaceutical emulsion comprising a neurokinase-1 (NK-1) receptor antagonist, an emulsifier, an oil, a co-surfactant comprising an alcohol, a tonicity agent, a pH modifier, and water. The emulsion is an oil-in-water emulsion for intravenous/parenteral administration, and it has a pH ranging from about 7.5 to 9.0 with a ratio of emulsifier to the NK-1 receptor antagonist ranging from about 18:1 to 22:1 (wt/wt%).
The formulations are described for prevention or treatment of chemotherapy-induced emesis, including chemotherapy-induced nausea and vomiting (CINV). The disclosed compositions can include dexamethasone sodium phosphate located in the aqueous phase, and the patent emphasizes physical/chemical stability criteria, including USP <729> droplet size and PFAT5 limits, while maintaining controlled pH and low crystal formation.
A preparation approach is described in which an oil phase is formed by combining an NK-1 receptor antagonist, an emulsifier, an alcohol, and an oil, and an aqueous phase is formed by combining water, a tonicity agent, a pH modifier, and optionally a buffer. The oil phase and aqueous phase are homogenized to generate the pharmaceutical emulsion, followed by sterilizing the pharmaceutical emulsion.
Claims Coverage
The document includes two independent claims that cover an injectable oil-in-water emulsion containing an NK-1 receptor antagonist with defined pH and component ratios, and a method of preparing and sterilizing that emulsion by forming oil and aqueous phases, homogenizing them, and sterilizing the resulting emulsion. The core coverage is organized around a defined emulsion formulation and a corresponding preparative and sterilization sequence.
Injectable NK-1 receptor antagonist emulsion with defined composition and ratios
An injectable pharmaceutical emulsion comprising an NK-1 receptor antagonist, 11 wt/wt % to 15 wt/wt % of an emulsifier, an oil, a co-surfactant comprising an alcohol, a tonicity agent, a pH modifier, and water, wherein the pH of the emulsion ranges from about 7.5 to 9.0 and the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt%).
Method for preparing and sterilizing an injectable NK-1 receptor antagonist emulsion
A method comprising combining an NK-1 receptor antagonist, an emulsifier, and an alcohol with an oil to generate an oil phase; combining water, a tonicity agent, a pH modifier, and optionally a buffer to generate an aqueous phase; homogenizing the oil phase with the aqueous phase to generate the pharmaceutical emulsion; and sterilizing the pharmaceutical emulsion.
The claim set protects an injectable pharmaceutical emulsion containing an NK-1 receptor antagonist and specified excipients with a defined pH and emulsifier-to-antagonist ratio, together with a method that forms an oil phase and an aqueous phase, homogenizes them into the emulsion, and sterilizes the emulsion.
Stated Advantages
Provides stable injectable pharmaceutical emulsion formulations meeting physical/chemical stability criteria, including USP <729> droplet size and PFAT5 limits, while maintaining controlled pH and low crystal formation.
Documented Applications
Prevention or treatment of chemotherapy-induced emesis, including chemotherapy-induced nausea and vomiting (CINV), using injectable formulations comprising an NK-1 receptor antagonist.
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