Parenteral formulation of the kappa agonist analgesic, DuP 747, via micellar solubilization.
The nonopioid kappa agonist analgesic amine, DuP 747, as a hydrochloride salt exhibited an aqueous solubility of 3 mg/ml. This solubility was insufficient to provide the desired dose in a solution formulation for intramuscular administration. Aqueous solutions of the hydrochloride salt exerted surface activity behavior; however, the critical micellar concentration (CMC) was not reached at the saturation solubility. Enhanced aqueous solubility required to reach the CMC could lead to micellization of the compound and a possible i.m. solution formula. The methanesulfonate salt was more water soluble than the hydrochloride salt and yielded a micellar solution with a concentration of 60 mg/ml.
Hussain
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MA
Du Pont Merck Pharmaceutical Co., Experimental Station, Wilmington, Delaware 19880-0400.
Wu
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Koval
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Hurwitz
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D000081:Acetamides / Q000008:administration & dosage / Q000737:chemistry*; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry*; D044482:Benzeneacetamides; D002851:Chromatography, High Pressure Liquid; D008823:Micelles; D011759:Pyrrolidines / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000737:chemistry*
D000081:Acetamides; D000700:Analgesics; D044482:Benzeneacetamides; D008823:Micelles; D011759:Pyrrolidines; D013764:Tetrahydronaphthalenes; C076987:DuP 747