Nonaqueous cephalosporin suspension for parenteral administration: cefazolin sodium.

The flocculation-deflocculation behavior of cefazolin sodium (I) in nonaqueous media and the effect of surfactants as measured by zeta potential, sedimentation, and porosity were studied. A significant difference in zeta potential was observed when the particles were suspended in different nonaqueous media. The addition of surfactant produced a deflocculated state. The surfactant deflocculated the particles by a process of supersaturation and crystallization involving a surfactant-cefazolin complex. The shielding effect of the surfactant on the surface of the particles also apparently affected their electrophoretic properties. Kinetic studies on the stability of the drug as a function of temperature were conducted; it appears that the chemical stability in ethyl oleate at room temperature is adequate for a reasonable shelf life. The efficiency of absorption of the drug from the ethyl oleate suspension was evaluated after intramuscular administration in dogs. The area under the plasma concentration versus time curve and urinary recovery indicated that cefazolin was 100% bioavailable from this nonaqueous preparation.