Dissociation constant of chlordiazepoxide in montmorillonite suspension and its pharmaceutical application for a...

The changes in the distribution of the ionic species of a drug due to interactions with a clay surface may have important consequences in drug therapy. The binding of chlordiazepoxide (CDO) into montmorillonite clay, veegum: HV (V), surface was studied under several pH conditions. In vitro drug release behaviour from CDO-V products was investigated. Changes in the partial molar free energy of the ionic species of CDO, delta Gi (i = CDO, CDOH+) as a result of interaction with V were determined by using differential absorbance spectroscopic techniques at 260 and 310 nm. The stronger interaction between the negatively charged clay surface and the protonated species (CDOH+) relative to the parent compound is responsible for the apparent displacement of its pKa value in V suspensions from 4.64 to 5.67. In vitro drug release behaviour from CDO-V product to the simulated gastrointestinal fluids showed a controlled pattern. The in vivo results indicated a prolonged drug effect after the oral administration of drug-clay preparation.