RT Journal Article SR Electronic T1 Parenteral Formulation Development for the Positive Inotropic Agent RS-82856: Solubility and Stability Enhancement Through Complexation and Lyophilization JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 120 OP 125 VO 41 IS 4 A1 Gary C. Visor A1 LI-HWA Lin A1 Eric Benjamin A1 Robert G. Strickley A1 Leo Gu YR 1987 UL http://journal.pda.org/content/41/4/120.abstract AB Parenteral formulation development for the positive inotropic agent N-cyclohexyl-N-methyl-4 (7-oxy-l,2,3,5-Tetrahydroimidazo[2,1-b] quinazolin-2-one) butyramide (RS-82856) involved adding a complexing agent to enhance aqueous solubility and lyophilizing complexed drug to provide adequate storage stability. Our studies indicate that RS-82856 forms water soluble complexes with various bio-organic ligands, and that the complexes significantly increase the total solubility of RS-82856. Phase solubility and differential-pulse voltammetry experiments were used to study the interactions between the drug and complexing agents. Of the four ligands investigated, ascorbic acid provided the greatest enhancement in drug solubility. Further improvements in solubility were also found to occur when the complex of RS-82856 with ascorbic acid was lyophilized from an aqueous/tert-butyl alcohol solution. This lyophilization process yielded a product with acceptable chemical and physical stability.