The application of a crosslinked pectin-based wafer matrix for gradual buccal drug delivery.

The purpose of this study was to develop crosslinked wafer matrices and establish the influence of the crosslinker type and processing sequence on achieving gradual buccal drug delivery. Three sets of drug-loaded crosslinked pectin wafers were produced employing the model water-soluble antihistamine, diphenhydramine and were compared with noncrosslinked wafers. The formulations were crosslinked with CaCl(2), BaCl(2), or ZnSO(4) pre- or postlyophilization (sets 1 and 2) as well as pre- and postlyophilization (set 3), respectively. The surface morphology, porositometry, molecular vibrational transitions, textural attributes, thermal and in vitro drug release were characterized and supported by in silico molecular mechanics simulations. Results revealed that crosslinked wafers produced smaller pore sizes (107.63 Å) compared with noncrosslinked matrices (180.53 Å) due to molecular crosslinks formed between pectin chains. Drug release performance was dependent on the wafer crosslinking production sequence. Noncrosslinked wafers displayed burst-release with 82% drug released at t(30min) compared with first-order kinetic profiles obtained for prelyophilized crosslinked matrices (50% released at t(30min) followed by steady release). Wafers crosslinked postlyophilization displayed superior control of drug release (40% at t(30min)). Molecular mechanics simulations corroborated with the experimental data and established that Ba(++), having the largest atomic radii (1.35 Å) formed a number of ionic bridges producing wafers of higher porosity (0.048 cm(2)/g) and had more influence on drug release.