Dissolution mechanisms: theoretical and experimental investigations

Recommended Citation Qiu, Yang. "Dissolution mechanisms: theoretical and experimental investigations. ABSTRACT Dissolution rate is an important indicator of drug bioavailability. In this work, a mixed-kinetic-controlled dissolution model was developed which encompasses transport control and interface control as limiting cases. This model is mathematically equivalent to two existing mixed-kinetic-control models, but provides physicochemical significance to the semi-empirical quantities in these models by treating a dissolving solid surface as a distribution of various types of detachment and re-deposition sites that interact with the solution according to chemical kinetic theory. The degree of interface control is determined by the ratio of the collective re-deposition rate constant to the transport rate constant. In the first experimental investigation, the intrinsic dissolution behavior of benzoic acid, salicylic acid and trans-cinnamic acid was investigated under different temperature (37°C , 10°C and 3° C) and agitation (50-800 rpm) conditions. These compounds dissolved by transport control at 37° C, but exhibited up to 27% interface control at lower temperatures, calculated from the plots of 1/J vs. ω-0.5 (J = dissolution rate, ω = rotational speed), and alternatively from the plots of ln J vs. ln ω. It was concluded that as the temperature decreases, the collective re-deposition rate constant decreases faster than the transport rate constant, thus shifting the dissolution mechanism towards interface control at low temperatures. In the second investigation, the intrinsic dissolution rate of benzoic acid as a function of agitation intensity was studied in water and various NaDS concentrations above the CMC at 25°C. The plots of J vs. ω 0.5 , fitted with the functional form of the derived mixed-kinetic-control model, indicate significant interface control. An extended dissolution model which features a micelle-interface interaction mechanism was proposed to give meaning to the fitting parameters iii and offer a possible explanation for their variation with the micelle concentration. The manner in which the parameter varies with mic C in the present study also suggests possible micellar activity effects. In the third investigation, the effects of FD&C Blue #1, a water-soluble dye on sulfathiazole dissolution were studied. It was shown that low concentrations (10-100 μg/mL) of the dye reduced the intrinsic dissolution rate of sulfathiazole by up to 34% in 0.1 N HCl, while the same levels of FD&C Blue #1 only slightly inhibited sulfathiazole dissolution in 0.01 N HCl and exhibited no effect in water. An adsorption mechanism was suggested in which the protonation of sulfathiazole …