Aprepitant Injectable Formulations

a technology of aprepitant and injection formulation, which is applied in the field of parenteral, can solve the problems of insufficient stability of such compositions in solution, the inability to achieve such soluble and stable formulations of aprepitant, and the addition of fosaprepitant to the drug. achieve the effect of significant stability

Inactive Publication Date: 2013-11-28
INNOPHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014]In an embodiment, the primary co-solvent is a short-chain alcohol, the surfactant is a non-ionic surfactant, and / or the secondary co-solvent is a short-chain polyethylene glycol or dimethylacetamide. In an embodiment the sterile aqueous diluent is water. Such kits will allow for the formulation of an aqueous, ready-to-use formulation of aprepitant in which the aprepitant remains in solution upon dilution with an aqueous diluent. Moreover, it should be noted that aprepitant in the formulations presented herein has significant stability, even upon prolonged storage in liquid form.

Problems solved by technology

However, the stability of such compositions in solution is generally insufficient.
However, notwithstanding numerous attempts to increase the solubility of aprepitant, aprepitant per se is available only in a formulation for oral administration.
However, the additional steps required for the synthesis of fosaprepitant add significant complexity and cost to the drug.
However, and to the best of the inventors' knowledge, no such soluble and stable formulation of aprepitant has been reported.

Method used

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  • Aprepitant Injectable Formulations

Examples

Experimental program
Comparison scheme
Effect test

example 2

[0040]20 mL of propylene glycol was mixed with 20 mL water followed by addition of 15 mL of glacial acetic acid, 1.0 g of tartaric acid and 5 mL of 2 N hydrochloric acid. 25 mg drug was dissolved separately in 0.5 mL of tetraglycol. The drug solution is added to the mixture of propylene glycol and acids gradually with constant stiffing. pH of solution was adjusted with 10 N NaOH gradually to pH 3 to 4 resulting in a clear, colorless, particulate free drug solution.

example 3

[0041]3.0 mL of propylene glycol was added to 20 mL water followed by addition of 3.0 g of tartaric acid. 25 mg of drug was dissolved in 0.5 mL of tetraglycol separately. This drug solution was added to the mixture of propylene glycol, tartaric acid and water. pH of this solution was 1.5. The solution was made alkaline by quick addition of 3 mL of 10 N NaOH. The resulting solution had pH of 10 and was clear and colorless with an approximate concentration of 1 mg / mL of aprepitant.

[0042]Thus, while the above approaches using complexing agents and / or co-solvents led to a soluble form of aprepitant in at least some instances, concentration of aprepitant is relatively low, and aprepitant tends to precipitate out upon further dilution. As is already known in the art, solubility of aprepitant increases exponentially with increasing concentration of ethanol as shown in Table 1 in the background section. Moreover, maximum allowed concentrations of ethanol in a drug formulation are typically ...

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Abstract

An aqueous stable and ready-to-use formulation of aprepitant is prepared. Especially preferred formulations comprise a synergistic combination of a co-solvent and a surfactant and may further include a secondary co-solvent. Among other advantages of contemplated formulations, aprepitant is dissolved at high concentrations and remains dissolved and stable, even over prolonged periods of time.

Description

[0001]This application claims priority to U.S. provisional application having Ser. No. 61 / 651501, which was filed May 24, 2012, and to U.S. provisional application having Ser. No. 61 / 798276, which was filed Mar. 15, 2013, both incorporated by reference herein.FIELD OF THE INVENTION[0002]The field of the invention is parenteral, and especially injectable dosage forms for the administration of aprepitant to an individual. In especially preferred dosage forms, aprepitant is in a stable and dissolved form.BACKGROUND[0003]Aprepitant (5-([(2R,3S)-2-((R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy)-3-(4-fluoro-phenyl)morpholino]methyl)-1H-1,2,4-triazol-3(2H)-one) is an antiemetic compound that belongs to the class of substance P antagonists that mediate their effect by blocking the neurokinin (NK1) receptor. Aprepitant is a selective, high-affinity antagonist at human substance P NK-1 receptors and is manufactured by Merck & Co. (available under the brand name, Emend®). It is available as ora...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/5377
CPCA61K31/5377A61K9/0019A61K47/10A61K47/18A61K47/24A61K47/26A61K47/44A61P1/08A61K9/08
Inventor HINGORANI, TUSHARSOPPIMATH, KUMARESHPEJAVER, SATISHPURI, NAVNEET
Owner INNOPHARMA
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