In vitro and in vivo chlorpromazine availability from flocculated polysalt complex systems

An insoluble drug-polysalt complex of chlorpromazine hydrochloride, sodium carboxymethylcellulose, and protamine sulfate was selected as a model to evaluate the effects of these macromolecular constituents on the in vitro and in vivo availability of the interacted drug. The in vitro liberation of drug from the polysalt complex was studied in simulated gastrointestinal fluids as a function of particle size, pH of formation of the complex flocculate, and presence and absence of enzymes in the medium. The in vitro drug-release studies conducted under these varying conditions suggested that the product possessed prolonged-release properties. In contrast, the in vivo studies with rats revealed a promoted bioavailability of the drug in the presence of the polysalt complex. Protamine sulfate, a known pinocytotic inducer, was observed to be specifically implicated in this phenomenon.