A ready to use injectable emulsion composition of aprepitant

Abstract

The present invention relates to an injectable emulsion composition comprising a therapeutically effective amount of aprepitant, one or more emulsifiers, and one or more long chain triglycerides. The composition is optionally devoid of alcohol solvent. The emulsion may comprise an emulsifier to long chain triglycerides ratio of 1 :2 to 1 :4 and may optionally include an antioxidant. The composition may be provided as a ready-to-use formulation. The invention further relates to processes for the preparation of the injectable emulsion composition.

Description

[0001] AN INJECTABLE EMULSION COMPOSITION OF APREPITANT CROSS-REFERENCE TO RELATED APPLICATION(S) This application claims priority from Indian Provisional Application Number IN202341059913, filed on September 06, 2023, entire contents of which are incorporated herein by reference in their entireties. The present invention relates to an injectable emulsion composition comprising therapeutically effective amount of aprepitant, one or more emulsifier and one or more long chain triglycerides. The injectable emulsion composition is optionally devoid of alcohol solvent. The injectable emulsion composition may further comprise one or more antioxidant. The injectable emulsion composition may be ready to use. BACKGROUND OF INVENTION Pharmaceutical emulsions are a mixture of two or more immiscible liquids that are partitioned by liquid-liquid phase separation. Many high affinity pharmaceutical molecules face challenges of achieving optimum effect due to their low solubility. Pharmaceutical injectable emulsions are promising delivery systems for such hydrophobic compounds wherein hydrophobic and hydrophilic phases are stabilized with an emulsifier. Aprepitant is a morpholine-based antiemetic, which is used for the prevention of acute and delayed nausea and vomiting. It is presently commercialized in the US market as an injectable lipid emulsion with tradename Cinvanti® and Aponvie®. However, there are limitations or problems with respect to the currently available RLD. ^ It contains alcohol which causes alcohol intoxication. e.g Docetaxel injection which is used for chemotherapy contains alcohol and FDA has raised a warning with respect to safety of patients which may cause patient to feel drunk during and after treatment. ^ It has to be diluted with sodium chloride or dextrose solution for IV infusion in an aseptic condition that may result is some dilution error. ^ The product is to be stored at 2-8°C. Therefore, it is indicative of high instability at room temperature. ^ The marketed injectable emulsion composition contains very high concentration (i.e 11-15% w / v) of egg lecithin which makes the bulk manufacturing process and handling difficult due to the low storage (i.e.- 20°C). Ottoboni et al – 1 (US20170112847A1) relates to single use high concentration emulsion composition of Aprepitant. It has very high concentration (i.e 11-15% w / v) of egg lecithin which makes the bulk manufacturing process and handling difficult due to the low storage (i.e.- 20°C). Ottoboni et al – 1 further discloses that liquid formulations containing aprepitant are very challenging and are prone to chemical, physical and / or thermodynamic degradation. The compositions of Ottoboni et al – 1 contains alcohol which has limitation of being prone to alcohol intoxication. e.g Docetaxel injection which is used for chemotherapy contains alcohol and FDA has raised a warning with respect to safety of patients which may cause patient to alcohol consumption effects during and after treatment. Ottoboni et al – 2 (US20170216205A1) relates to single use high concentration emulsion composition of aprepitant with the pH of the emulsion in ranges from about 7.5 to 9.0. The disclosed compositions has similar drawbacks as aforementioned for Ottoboni et al – 1. Hingorani et al (US20170136027A1) relates to ready to use aprepitant injectable composition containing multiple solvent system including alcohol like ethanol. Akasapu et al (US20210212933A1) relates to ready to use aprepitant injectable composition free of long chain triglycerides and ethanol. Therefore, there is an urgent need to develop injectable emulsion composition with are safe, stable, easy to administer and easy to manufacture. There is an urgent need to develop ready to use injectable emulsion composition with are safe, stable, easy to administer and easy to manufacture. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to injectable emulsion composition comprising therapeutically effective amount of aprepitant, one or more emulsifier and one or more long chain triglycerides. The injectable emulsion composition is optionally devoid of alcohol solvent. The injectable emulsion composition may further comprise one or more antioxidant. The present invention relates to a ready to use injectable emulsion composition comprising therapeutically effective amount of aprepitant, one or more emulsifier and one or more long chain triglycerides. The injectable emulsion composition is optionally devoid of alcohol solvent. The injectable emulsion composition may further comprise one or more antioxidant. In one or more embodiments, the present invention relates to injectable emulsion composition comprising a. therapeutically effective amount of aprepitant, b. one or more emulsifier, and c. one or more long chain triglycerides, wherein the said composition is devoid of alcohol solvent. In a preferred embodiment, the said composition is devoid of ethanol. In one or more embodiments, the present invention relates to injectable emulsion composition comprising a. therapeutically effective amount of aprepitant, b. one or more emulsifier, and c. one or more long chain triglycerides, wherein the said composition is stable at ambient room temperature. In certain embodiments, the composition of the invention comprises emulsifier to long chain triglycerides in a ratio of 1:2 to 1:4. In certain embodiments, the ready to use injectable emulsion composition is devoid of polar organic solvents. In one or more embodiments, the present invention relates to injectable emulsion composition comprising a. therapeutically effective amount of aprepitant, b. one or more emulsifier, c. one or more triglycerides, and d. at least one antioxidant. In a certain, preferred embodiments, the triglyceride is long chain triglycerides. In one or more embodiments, the present invention relates to ready to use injectable emulsion composition comprising d. therapeutically effective amount of aprepitant, e. one or more emulsifier, and f. one or more long chain triglycerides, wherein the said composition is devoid of alcohol solvent. In a preferred embodiment, the said composition is devoid of ethanol. In one or more embodiments, the present invention relates to ready to use injectable emulsion composition comprising d. therapeutically effective amount of aprepitant, e. one or more emulsifier, and f. one or more long chain triglycerides, wherein the said composition is stable at ambient room temperature. In certain embodiments, the composition of the invention comprises emulsifier to long chain triglycerides in a ratio of 1:2 to 1:4. In certain embodiments, the ready to use injectable emulsion composition is devoid of polar organic solvents. In one or more embodiments, the present invention relates to ready to use injectable emulsion composition comprising e. therapeutically effective amount of aprepitant, f. one or more emulsifier, g. one or more triglycerides, and h. at least one antioxidant. In a certain preferred embodiments, the triglyceride is long chain triglycerides. Aprepitant is a substance P / neurokinin 1 (NK1) receptor antagonist, an antiemetic agent. Its empirical formula is C23H21F7N4O3, and its structural formula is: is sparingly soluble in ethanol and isopropyl acetate and slightly soluble in acetonitrile. Aprepitant is indicated for the prevention of postoperative nausea and vomiting. Currently, marketed injectable emulsion composition APONVIE (aprepitant) is a single-dose vial for intravenous use. Each vial contains 32 mg aprepitant in 4.4 mL of emulsion. The emulsion also contains the following inactive ingredients: ^ dehydrated alcohol (0.13 g), ^ egg lecithin (0.64 g), ^ sodium oleate (0.02 g), ^ soybean oil (0.42 g), ^ sucrose (0.24 g), and ^ water for injection (2.97 g) Currently, marketed injectable emulsion composition Cinvanti and Aponvie is stable only upto 6 hr at room temperature or at 25°C with sodium chloride in diluted form. The injectable emulsion composition as per present invention may be alcohol solvent free composition that reduces the risk of intravenous use of Aprepitant injectable emulsion or in combination of cancer drug therapy esp. alcohol intoxication. The ready to use injectable emulsion composition as per present invention requires no further dilution. Therefore, the risk with respect to aseptic condition as well as medication error with respect to dilution will be eliminated. Further, shortage of diluent in the market will have no impact on the ready to use injectable emulsion composition as per present invention. The injectable emulsion composition as per present invention contains low concentration of egg lecithin which improves the process as well as handling of the product during manufacturing. The injectable emulsion composition may contain different inactive ingredient like oil, emulsifier, buffer, antioxidants etc. In a more preferred embodiment, the ready to use injectable emulsion composition as per present invention comprises low concentration of egg lecithin, soybean oil, sucrose, sodium chloride, sodium hydroxide and / or alpha tocopherol. An oil phase in the emulsion assists in solubilisation or dispersion of the active pharmaceutical ingredient. Non limiting examples of oil includes soybean oil, coconut oil, olive oil, safflower oil, medium chain triglycerides, or a mixture thereof. The amount of oil in the emulsion may be in the range of 10% to 30%. In certain preferred embodiments composition as per invention comprises long chain triglycerides as oil. In certain specific embodiments, composition comprises soybean oil is within concentration of 5-15% v / v . Emulsion are prone to thermodynamic instability leading to physical breaking. Emulsifiers reduces interfacial tension of emulsions by providing surface charge that repels globules and thereby stabilizes it. Non limiting examples of emulsifier includes phospholipid, Polyethylene Glycols (PEGs), Poloxamers etc. In certain preferred embodiments composition as per invention comprises lecithin as emulsifier, more preferably egg lecithin within the range of 1.2% - 5% w / v. The amount of emulsifier in the emulsion may be in the range of 0.5% to 5.0%. Non limiting examples of tonicity adjusting agent includes sucrose, dextrose, glycerin, mannitol, sodium chloride. They are part of the water phase in the emulsion. The amount of tonicity adjusting agent in the emulsion may be in the range of 0.1% to 7.0%. In certain specific embodiments, composition comprises sucrose at a concentration of 2- 10% w / v for tonicity adjusting agent. Non limiting examples of buffering agents in compositions includes phosphate buffer, citrate buffer, Tris buffer, carbonate buffer, succinate buffer, maleate buffer or borate buffer. Non limiting examples of pH adjusting agent includes sodium hydroxide, potassium hydroxide, magnesium hydroxide, sodium carbonate, Tris or mixtures thereof. In certain preferred embodiments, composition as per invention comprises sodium hydroxide or tris buffer as pH adjusting agent Non limiting examples of antioxidants includes vitamin E, vitamin C, selenium. In certain preferred embodiments, composition as per invention comprises alpha tocopherol as an antioxidant. The amount of antioxidants in the emulsion may be in the range of 0.01% to 1%. The ready to use injectable emulsion composition as per invention may be prepared using techniques known in the art. In more preferred embodiments, composition as per invention may be prepared using high pressure homogenization. The ready to use injectable emulsion composition as per invention may be sterilized using aseptic filtration or terminal sterilization autoclaving method. In more preferred embodiments, composition as per invention may be sterilized using terminal sterilization autoclaving method. The injectable emulsion composition as per invention may be packaged in glass bottle or bags. In more preferred embodiments, composition as per invention may be packaged in glass bottles with rubber closure such as bromobutyl and chlorobutyl. Having described the invention with reference to the different embodiments of the invention, other embodiments will become apparent to one skilled in the art from consideration of the specifications. The innovation is further defined by reference to the following examples. It will be apparent to those skilled in the art that many modifications to the composition may be practiced without departing from the scope of this invention.

[0002] EXAMPLES Example – 1 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Sodium chloride 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 7 Sodium hydroxide 0.001 0.118 0.10 8 WFI 0.680 80.24 68.10 1.0 118mL 100.00 pH: 5-7 Example – 2 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Dextrose 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 7 Sodium hydroxide 0.001 0.118 0.10 8 WFI 0.680 80.24 68.10 1.0 118mL 100.00 pH: 6-7 Example – 3 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Mannitol 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 7 Sodium hydroxide 0.001 0.118 0.10 8 WFI 0.680 80.24 68.10 1.0 118mL 100.00 pH:4-7 Example – 4 Sl. No Ingredients g / mL g / 114mL Percentage 1 Aprepitant 0.00088 0.100 0.09 2 Sodium chloride 0.009 1.026 0.90 3 Egg lecithin 0.05 5.7 5.00 4 Sodium oleate 0.005 0.57 0.50 5 Soybean oil 0.200 22.8 20.00 6 Sucrose 0.0539 6.15 5.39 7 Sodium hydroxide 0.001 0.114 0.10 8 WFI 0.680 77.56 68.10 1.0 114mL 100.00 pH: 5-7 Example – 5 Sl. No Ingredients g / mL g / 114mL Percentage 1 Aprepitant 0.00088 0.100 0.09 2 Dextrose 0.009 1.026 0.90 3 Egg lecithin 0.05 5.7 5.00 4 Sodium oleate 0.005 0.57 0.50 5 Soybean oil 0.200 22.8 20.00 6 Sucrose 0.0539 6.15 5.39 7 Sodium hydroxide 0.001 0.114 0.10 8 WFI 0.680 77.56 68.10 1.0 114mL 100.00 pH:5-7 Example – 6 Sl. No Ingredients g / mL g / 114mL Percentage 1 Aprepitant 0.00088 0.100 0.09 2 Mannitol 0.009 1.026 0.90 3 Egg lecithin 0.05 5.7 5.00 4 Sodium oleate 0.005 0.57 0.50 5 Soybean oil 0.200 22.8 20.00 6 Sucrose 0.0539 6.15 5.39 7 Sodium hydroxide 0.001 0.114 0.10 8 WFI 0.680 77.56 68.10 1.0 114mL 100.00 pH: 5-7 Example – 7 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Sodium chloride 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 Sodium hydroxide / 7 tris buffer Q.s to pH 4- 7 8 All rac alpha tocopherol 0.002 0.027 0.20 9 WFI 0.680 80.24 68.10 1.0 118mL 100.00 Example – 8 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Dextrose 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 Sodium hydroxide / 7 tris buffer Q.s to pH 4- 7 8 All rac alpha tocopherol 0.002 0.027 0.20 9 WFI 0.680 80.24 68.10 1.0 118mL 100.00 Example – 9 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Mannitol 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 Sodium hydroxide / 7 tris buffer Q.s to pH 4- 7 8 All rac alpha tocopherol 0.002 0.027 0.20 9 WFI 0.680 80.24 68.10 1.0 118mL 100.00 Example – 10 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Sodium chloride 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 Sodium hydroxide / 7 Tris buffer Q.s to pH 4-7 8 All rac alpha tocopherol 0.002 0.027 0.20 9 WFI 0.680 80.24 68.10 1.0 118mL 100.00 Example – 11 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Dextrose 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 Sodium hydroxide / 7 Tris buffer Q.s to pH 4-7 8 All rac alpha tocopherol 0.002 0.027 0.20 9 WFI 0.680 80.24 68.10 1.0 118mL 100.00 Example – 12 Sl. No Ingredients g / mL g / 118mL Percentage 1 Aprepitant 0.0011 0.130 0.11 2 Mannitol 0.009 1.062 0.90 3 Egg lecithin 0.05 5.9 5.00 4 Sodium oleate 0.005 0.59 0.50 5 Soybean oil 0.2 23.6 20.00 6 Sucrose 0.0539 6.36 5.39 Sodium hydroxide / 7 Tris buffer Q.s to pH 4-7 8 All rac alpha tocopherol 0.002 0.027 0.20 9 WFI 0.680 80.24 68.10 1.0 118mL 100.00 Example 1 to 12 - Process for preparation of ready to use composition: 1. Collection of WFI - Collected WFI and purged with nitrogen for 30 minutes. 2. Dispensing - Dispensed API and excipients. 3. Preparation of oil phase - In a beaker, required qty of Soybean oil was dispensed. In another beaker, dispensed qty of API was transferred and to this above collected soybean oil 50% of batch qty was added and mixed well till we get a good dispersion of API. Then added remaining soybean oil solution for rinsing the API dispersion beaker. 4. Preparation of Aqueous phase - In a glass beaker, 150mL of nitrogen purged WFI is collected and kept on heating at 40-45°C. To this dispensed qty of Egg lecithin was added and mixed under stirrer for 20 minutes at 2500 rpm. In a clean and dried beaker, WFI was collected and to this dispensed qty of sucrose and sodium chloride was added and dissolved by mixed well. This solution was added to the above Step4. under continuous stirring at 3000 rpm at 40°C. 5. Mixing of oil phase and aqueous phase under lab stirrer. To the aq phase oil phase of was added slowly under lab stirrer at 4000 rpm, continued stirring for 10 min at 4000 rpm at RT. In a clean and dried beaker, WFI was collected and to this dispensed qty of sodium oleate was added and mixed well and added to the above step. To the above step 0.1N NaoH or tris buffer was added to adjusted the pH within range of 4-7 and continued stirring for 10 min. Mixed for 15 minutes. 6. Fluidization by High pressure homogenizer Above bulk was Micro Fluidization, fluidized the bulk emulsion was processed at 1500bar for 8-10 passes. 7. Sterilization - aseptic filtration through 0.2 micron nylon filter or autoclave. Example 13 Sl. No Ingredients g / mL g / 18mL Percentage 1 Aprepitant 0.0072 0.130 0.72 3 Egg lecithin 0.05 0.9 5.00 4 Sodium oleate 0.005 0.09 0.50 5 Soybean oil 0.200 3.6 20.00 6 Sucrose 0.0539 0.97 5.39 Sodium 7 hydroxide Q.s. to pH 4-7 8 WFI 0.690 12.42 69.0 1.0 18mL 100.00 Example 14 Sl. No Ingredients g / mL g / 4.4mL Percentage 1 Aprepitant 0.0072 0.032 0.72 3 Egg lecithin 0.05 0.22 5.00 4 Sodium oleate 0.005 0.022 0.50 5 Soybean oil 0.200 0.88 20.00 6 Sucrose 0.0539 0.237 5.39 7 Sodium hydroxide Q.s. to pH 4-7 8 WFI 0.690 3.036 69.0 1.0 4.4mL 100.00 Example 13 to 14 - Process for preparation of ready to use composition. 1. Collection of WFI - Collected WFI and purged with nitrogen for 30 minutes. 2. Dispensing - Dispensed API and excipients in clean and dried glass beaker and weighing pans. 3. Preparation of oil phase - In a beaker, required qty of Soybean oil was dispensed. In another beaker, dispensed qty of API was transferred and to this above collected soybean oil 50% of batch qty was added and mixed well till we get a good dispersion of API. Then added remaining soybean oil solution for rinsing the API dispersion beaker. 4. Preparation of Aqueous phase - In a glass beaker 150mL of nitrogen purged WFI is collected and kept on heating at 40-45°C. To this dispensed qty of Egg lecithin was added and mixed under stirrer for 20 minutes at 2500 rpm. In a clean and dried beaker, WFI was collected and to this dispensed qty of sucrose was added and dissolved by mixed well. This solution was added to the above Step4. under continuous stirring at 3000 rpm at 40°C. 5. Mixing of oil phase and aqueous phase under lab stirrer To the aq phase oil phase was added slowly under lab stirrer at 4000 rpm, continued stirring for 10 min at 4000 rpm at RT. In a clean and dried beaker, WFI was collected and to this dispensed qty of sodium oleate was added and mixed well and added to the above step. To the above step 0.1N NaoH was added and continued stirring for 10 min. Mixed for 15 minutes. 6. Fluidization by High pressure homogenizer Above bulk was taken for Fluidization, fluidized the bulk emulsion was processed at 1500bar for 8passes. 7. Sterilization - aseptic filtration through 0.2 micron nylon filter or autoclave Example 15: Sl. No Ingredients mg / mL mg / 118mL % Input 1 Aprepitant 1.10 130.0 0.11 2 Egg lecithin 20.00 2360.0 2.00 3 Sodium oleate 0.70 82.6 0.07 4 *Soybean oil 200.00 23600.0 20.00 5 Glycerine 22.00 2596.0 2.20 6 Sodium hydroxide Qs to pH Qs to pH Qs to pH 7 WFI Qs to 1mL Qs to 118mL Qs to 100% * Contains alpha tocopherol. Example 16: Sl. No Ingredients mg / mL mg / 114mL % Input 1 Aprepitant 0.877 100.0 0.088 2 Egg lecithin 20.000 2280.0 2.00 3 Sodium oleate 0.700 79.8 0.07 4 *Soybean oil 200.000 22800.0 20.00 5 Glycerine 22.000 2508.0 2.20 6 Sodium hydroxide Qs to pH Qs to pH Qs to pH 7 WFI Qs to 1mL Qs to 114mL Qs to 100% * Contains alpha tocopherol. Procedure: Collection Water for injection was collect in a vessel and purged with Step 1. of WFI nitrogen for 30 minutes API and excipients were dispensed in clean and dried glass Step 2. Dispensing beaker Batch qty of Soybean oil was dispensed and kept on heating at 40-45°C. To this heated soybean oil Egg lecithin was Preparation Step 3. added and mixed under stirrer for 20 minutes at 2500 rpm. of oil phase Temperature of above dispersion was cool down to 20°C to 25°C. Dispensed qty of API was transferred to the above dispersion and mixed under stirrer for 20 minutes at 2500 rpm, till get a good dispersion. In 50 mL of WFI nitrogen was purged and collected in a beaker. To the nitrogen purged WFI water dispensed qty of Glycerin was added and mixed under stirrer for 10 minutes Preparation at 500 rpm, to get a clear solution. Step 4. of Aqueous In 150 mL WFI nitrogen was purged and collected in a phase beaker. To this dispensed qty of nitrogen purged sodium oleate was added and mixed under stirrer for 20 minutes at 500 rpm, to get a clear solution To the aqueous phase of step 4., oil phase of Step 3 was added slowly under lab stirrer at 4000 rpm. Further it was Mixing of continued stirring for 10 mins at 4000 rpm at RT. oil phase Glycerin solution and sodium oleate solution of step 4. were Step 5. and aqueous added to above step of aqueous and oil phase mixture, one phase under after other and mixed well for 10 minutes. lab stirrer 0.1N NaOH was added to the bulk emulsion to maintain the pH to 6.0 to 9.0 and continued stirring for 10 min. Further the bulk emulsion was mixed for 15 minutes Fluidization by High Above bulk emulsion was subjected to fluidization / size Step 6. pressure reduction at 1500bar for 8passes. homogenize r Above processed bulk emulsion was filtered with 0.2µm Step 7. Filtration Nylon membrane filter. Filling and Above filtered emulsion was filled in IV infusion bags and Step 8. terminal stoppered and subjected to sterilization at 121°C for 15 sterilization minutes. Example 17: Single IV push composition: Sl. No Ingredients mg / mL mg / 18mL % Input 1 Aprepitant 7.2 130.0 0.72 2 Egg lecithin 30.0 540.0 3.00 3 Sodium oleate 10.0 180.0 1.00 4 *Soybean oil 200.0 3600.0 20.00 5 Sucrose 53.9 970.2 5.39 6 Sodium hydroxide Qs to pH Qs to pH Qs to pH 7 WFI Qs to 1mL Qs to 18mL Qs to 100% * Contains alpha tocopherol. Procedure Single IV push: Collection of Water for injection was collect in a vessel and purged Step 1. WFI with nitrogen for 30 minutes API and excipients were dispensed in clean and dried Step 2. Dispensing glass beaker. Batch qty of Soybean oil was dispensed and kept on heating at 40-45°C. To this heated soybean oil Egg lecithin was added and mixed under stirrer for 20 minutes at 2500 rpm. Preparation Step 3. Temperature of above dispersion was cool down to of oil phase 20°C to 25°C. Dispensed qty of API was transferred to the above dispersion and mixed under stirrer for 20 minutes at 2500 rpm, till get a good dispersion. In 50 mL of WFI nitrogen was purged and collected in a beaker. To the nitrogen purged WFI water dispensed qty of Glycerin was added and mixed under stirrer for Preparation 10 minutes at 500 rpm, to get a clear solution. Step 4. of Aqueous In 150 mL WFI nitrogen was purged and collected in a phase beaker. To this dispensed qty of nitrogen purged sodium oleate was added and mixed under stirrer for 20 minutes at 500 rpm, to get a clear solution To the aqueous phase of step 4., oil phase of Step 3 was added slowly under lab stirrer at 4000 rpm. Further it was continued stirring for 10 mins at 4000 rpm at RT. Mixing of oil Glycerin solution and sodium oleate solution of step 4. phase and were added to above step of aqueous and oil phase Step 5. aqueous mixture, one after other and mixed well for 10 minutes phase under 0.1N NaOH was added to the bulk emulsion to lab stirrer maintain the pH to 6.0 to 9.0 and continued stirring for 10 min. Further the bulk emulsion was mixed for 15 minutes Fluidization by High Above bulk emulsion was subjected fluidization / size Step 6. pressure reduction at 1500bar for 8passes. homogenizer Above processed bulk emulsion was filtered with Step 7. Filtration 0.2µm Nylon membrane filter. Example 18: Ingredients mg / 18mL Aprepitant 130.00 Egg lecithin 540.00 Sodium oleate 180.00 *Soybean oil 3600.00 Sucrose 970.20 Glycerine - Sodium hydroxide Qs to pH WFI Qs to 18mL Example 18 Ingredients mg / mL Aprepitant 1.10 Sodium chloride 9.00 Egg lecithin 50.00 Sodium oleate 5.00 Soybean oil 200.00 Sucrose 53.90 Sodium hydroxide Qs to pH 6 to 9 WFI Qs to 1mL Tests / Parameters Initial 3M Assay 97.0 96.6 pH 8.56 Osmolality 733 Related Substances Unknown Impurity ND Desfluoro Impurity 0.14% Total Impurities 0.14% Globule size distribution Globule size - D10 93.9 60.68 Globule size - D50 150 246.3 Globule size - D90 243 528.2 Z-Average 142.2 175.2 PDI 0.114 0.4006 Zeta Potential -15.9 NP

Claims

CLAIMS 1. An injectable emulsion composition comprising a. therapeutically effective amount of aprepitant, b. one or more emulsifier, and c. one or more long chain triglycerides, wherein the said composition is devoid of alcohol solvent.

2. The injectable emulsion composition according to claim 1, wherein emulsifier to long chain triglycerides is in a ratio of 1:2 to 1:

4.

3. The injectable emulsion composition according to claim 1, wherein said composition is devoid of polar organic solvents.

4. An injectable emulsion composition comprising a. therapeutically effective amount of aprepitant, b. one or more emulsifier, and c. one or more long chain triglycerides, wherein the said composition is stable at ambient room temperature.

5. The injectable emulsion composition according to claim 4, wherein emulsifier to long chain triglycerides in a ratio of 1:2 to 1:

4.

6. The injectable emulsion composition according to claim 4, wherein said composition is devoid of polar organic solvents.

7. An injectable emulsion composition comprising a. a therapeutically effective amount of aprepitant, b. one or more emulsifier, c. one or more triglycerides, and d. at least one antioxidant.

8. The injectable emulsion composition according to claim 7, wherein said triglyceride is long chain triglycerides.

9. The injectable emulsion composition according to claim 7, wherein emulsifier to long chain triglycerides in a ratio of 1:2 to 1:

4.

10. The injectable emulsion composition according to claim 7, wherein said composition is devoid of polar organic solvents.

11. A ready to use injectable emulsion composition comprising d. therapeutically effective amount of aprepitant, e. one or more emulsifier, and f. one or more long chain triglycerides, wherein the said composition is devoid of alcohol solvent.

12. The ready to use injectable emulsion composition according to claim 1, wherein emulsifier to long chain triglycerides is in a ratio of 1:2 to 1:

4.

13. The ready to use injectable emulsion composition according to claim 1, wherein said composition is devoid of polar organic solvents.

14. A ready to use injectable emulsion composition comprising d. therapeutically effective amount of aprepitant, e. one or more emulsifier, and f. one or more long chain triglycerides, wherein the said composition is stable at ambient room temperature.

15. The ready to use injectable emulsion composition according to claim 4, wherein emulsifier to long chain triglycerides in a ratio of 1:2 to 1:

4.

16. The ready to use injectable emulsion composition according to claim 4, wherein said composition is devoid of polar organic solvents.

17. A ready to use injectable emulsion composition comprising e. a therapeutically effective amount of aprepitant, f. one or more emulsifier, g. one or more triglycerides, and h. at least one antioxidant.

18. The ready to use injectable emulsion composition according to claim 7, wherein said triglyceride is long chain triglycerides.

19. The ready to use injectable emulsion composition according to claim 7, wherein emulsifier to long chain triglycerides in a ratio of 1:2 to 1:

4.

20. The ready to use injectable emulsion composition according to claim 7, wherein said composition is devoid of polar organic solvents.

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