In vitro method for detecting precipitation of parenteral formulations after injection

Abstract

Many injectable formulations currently on the market, including diazepam and alprazolam, utilize one or more cosolvents to solubilize the active constituents. On injections into an aqueous medium, some of these components tend to precipitate. A simple procedure is described for measuring the degree of precipitation that occurs when a solubilized drug is injected. This in vitro technique was used to show that alprazolam injection shows less precipitation than diazepam injection under all tested conditions, and that the precipitation observed with diazepam can be controlled by ensuring that the formulation is injected very slowly. This simple technique also can be used during preformulation development to evaluate the relative potential for precipitation of various formulations.