A novel channel flow method in determination of solubility properties and dissolution profiles of theophylline tablets

Abstract

A recently developed channel flow dissolution method was applied in the determination of compound solubility and the dissolution profiles of theophylline tablet formulations. As reference methods were used the USP basket and intrinsic dissolution methods. The four tablet compositions studied contained various proportions of lactose, microcrystalline cellulose (MCC), talc and magnesium stearate as pharmaceutical ingredients. The equilibrium constants of the dissolution reaction of theophylline (describing the relation between the dissolution and precipitation rate constants) in the individual tablet formulations, determined by the channel flow method, were similar at pH values of 1.2 and 6.8. The intrinsic dissolution rate of theophylline was slightly increased (from 0.9 to 1.1mg/(cm2min)) as the pH of the medium was decreased. There were clear differences between the results of channel flow and USP basket methods. In the channel flow apparatus the two formulations including the highest amounts of MCC liberated the drug substance the slowest, while with the USP basket method the compositions including either MCC alone or the highest amount of lactose liberated the drug substance the slowest. These release profiles were caused by the different disintegration behaviour of the tablets in the two methods. The advantages of the channel flow method include the analysis of solubility properties of the drug substance and, in particular, when compared to the USP basket method, the study of the early stages of the dissolution process.