CONTROLLED RELEASE OF THEOPHYLLINE FROM CROSS-LINKED AMYLOSE TABLETS

Amylose cross-linked (CLA) by epichlorohydrin treatment is introduced as a matrix for controlled release of drugs. Different reticulation degrees were obtained by varying the ratio of epichlorohydrin to amylose. A linear release of theophylline from the CLA tablets was observed in all cases. Linear increase of the cross-linking degree of the CLA used for tablet preparation generated non-linear diminution of the release time. For tablets obtained from CLA-7.5 (the lowest reticulation degree, realized by cross-linking of 100 g of amylose with 7.5 g of epichlorohydrin) containing theophylline up to 20% (w/w), a close to linear release was found over a period up to 15 h. For moderate increase of the cross-linking degree (CLA-12 and CLA-20) the release time was drastically decreased to 1-2 h. Release retardation in CLA-7.5 tablets seems to be related to the high amylose hydrogen interchain associations. Equilibrium swelling experiments in water and in 8 M urea support this hypothesis. The duration of the near-linear slow release was related to the duration of tablet swelling. The analysis of the data indicates that an anomalous release mechanism controls the transport of the drug; this includes neither Fickian diffusion nor glassy/rubbery transition. A hypothesis of a type of release controlled by hydrogen association is advanced.