JP-2022531685-A5 -

Dates

Publication Date

20230515

Application Date

20200507

Description

Figure 6 shows a comparison of the mean plasma concentration of methylnaltrexone with the time after administration of a self-emulsifying drug delivery system containing methylnaltrexone-docusate prepared according to Section 2.4 above. The highest plasma concentration of methylnaltrexone, approximately 8,000 ng/mL, was observed in dogs 5 within 1 hour of administration. The present invention encompasses the following embodiments. (Embodiment 1) (a) Formula: An ion pair having (wherein R- is an anion selected from the group consisting of lauryl sulfate and docusate); and (b) Oils, surfactants, cosolvents, or combinations thereof A pharmaceutical composition in liquid oral dosage form containing the following. (Embodiment 2) The pharmaceutical composition according to Embodiment 1, wherein R- is lauryl sulfate. (Embodiment 3) The pharmaceutical composition according to Embodiment 1, wherein R- is docusate. (Embodiment 4) A pharmaceutical composition according to any one of Embodiments 1 to 3, comprising the ion pairs in an amount of approximately 1% to approximately 75% by weight, approximately 10% to approximately 60% by weight, approximately 15% to approximately 50% by weight, or approximately 20% to approximately 40% by weight. (Embodiment 5) The pharmaceutical composition according to any one of Embodiments 1 to 4, wherein the oil comprises at least one of glyceryl monooleate, glyceryl monolinoleate, propylene glycol dicaprylate/dicaprate, soybean oil, polyglyceryl-3 dioleate, oleic acid, glyceryl caprylate, intermediate chain triglycerides, and combinations thereof. (Embodiment 6) The pharmaceutical composition according to any one of Embodiments 1 to 5, wherein the oil comprises glyceryl monolinoleate. (Embodiment 7) The pharmaceutical composition according to any one of Embodiments 1 to 6, wherein the oil contains oleic acid. (Embodiment 8) The pharmaceutical composition according to any one of Embodiments 1 to 7, wherein the oil comprises glyceryl caprylate. (Embodiment 9) The pharmaceutical composition according to any one of Embodiments 1 to 8, wherein the oil comprises an intermediate chain triglyceride. (Embodiment 10) The pharmaceutical composition according to any one of Embodiments 1 to 9, wherein the oil comprises glyceryl caprylate and intermediate chain triglycerides. (Embodiment 11) A pharmaceutical composition according to any one of Embodiments 1 to 10, comprising at least two types of oils. (Embodiment 12) The pharmaceutical composition according to any one of Embodiments 1 to 11, wherein the total oil content of the pharmaceutical composition is about 10% to about 80% by weight, about 10% to about 20% by weight, about 20% to about 50% by weight, or about 50% to about 70% by weight. (Embodiment 13) A pharmaceutical composition according to any one of Embodiments 1 to 12, comprising at least two surfactants. (Embodiment 14) The pharmaceutical composition according to any one of Embodiments 1 to 13, wherein the surfactant is selected from the group consisting of oleoyl polyoxyl-6 glyceride, linoleoyl polyoxyl-6 glyceride, caprylocaproyl polyoxyl-8 glyceride, polysorbate 80, polyoxyl 40 hydrogenated castor oil, polyoxyl 15 hydroxystearate, lauroyl polyoxyl-32 glyceride, and combinations thereof. (Embodiment 15) The pharmaceutical composition according to Embodiment 13 or 14, wherein the surfactant comprises caprylocaproyl polyoxyl-8 glyceride. (Embodiment 16) The pharmaceutical composition according to Embodiment 13 or 14, wherein the surfactant comprises polysorbate 80. (Embodiment 17) The pharmaceutical composition according to Embodiment 13 or 14, wherein the surfactant comprises linoleoyl polyoxyl-6 glyceride. (Embodiment 18) A pharmaceutical composition according to any one of Embodiments 1 to 17, comprising the surfactant in an amount of approximately 10% to approximately 70% by weight, approximately 15% to approximately 40% by weight, or approximately 20% to approximately 35% by weight. (Embodiment 19) A pharmaceutical composition according to any one of Embodiments 1 to 18, comprising the aforementioned ion pairs in amounts of approximately 1 mg to approximately 100 mg, approximately 50 mg to approximately 900 mg, approximately 75 mg to approximately 850 mg, approximately 100 mg to approximately 850 mg, approximately 150 mg to approximately 850 mg, approximately 200 mg to approximately 800 mg, or approximately 200 mg to approximately 700 mg. (Embodiment 20) A pharmaceutical composition according to any one of Embodiments 1 to 19, comprising at least about 1 mg, about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, or about 900 mg of the aforementioned ion pairs. (Embodiment 21) A pharmaceutical composition according to any one of embodiments 13 to 20, further com