The influence of fillers on theophylline release from clay matrices

Abstract: The objectives of this study were to investigate the suitability of magnesium aluminium silicate (MAS) (Veegum®) to control drug release of a model drug, theophylline, from tablet matrices. To this end, the performance of three commonly used fillers namely: lactose, microcrystalline cellulose (Avicel PH102; MCC), and pre-gelatinized starch, Starch 1500 PGS), were evaluated against Veegum®. The physico-mechanical properties of the tablet matrices were studied along with dissolution studies to determine the effect of single or binary mixtures of the excipients on the drug release pattern. A DSC hydration methodology was also employed to characterize the states of water present in the tablet matrices and to determine any impact on drug release. Formulations containing MAS alone produced compacts with the lowest hardness (4.5 kp) whereas formulations containing MCC alone produced the hardest tablets (17.2 kp). Dissolution studies suggested that matrices containing MAS alone released the theophylline quickest as compared to lactose, MCC or PGS. It was difficult to establish a trend of the bound and free water states in the tablet matrices; however the formulation containing only MAS had the highest bound water at 29 %. The results therefore show that theophylline does not interact with MAS. As such the dominant factor in controlling drug release using MAS requires interaction or intercalation with a cationic drug. In the absence of this however, other excipients can play a role in controlling drug release.
Keywords: Veegum, clay matrices, DSC hydration, Magnesium aluminium silicate, fillers