Structure-properties relationship in cross-linked high-amylose starch for use in controlled drug release

Cross-linked high-amylose starch (CLHAS), obtained by high-amylose starch c ross-linking, was recently introduced as an excipient (Contramid(TM)) for m onolithic dosage forms that are able to control drug release over 18-24 h. These control properties are related to tablet swelling and are strongly de pendent on the degree of the cross-linking of CLHAS. The permeability of so lutes through CLHAS hydrogels depends on the chemical structure of the poly mer. The aim of this study was to obtain a better understanding of how modi fications in CLHAS molecular structures at the level of long-range and shor t-range order during the cross-linking and processing conditions relate to the release properties of the CLHAS matrices. Structural parameters such as crystallinity contribute significantly to the physical and mechanical aspe cts of starch products. X-ray diffractometry, FTIR spectroscopy, dissolutio n tests in vitro, and mechanical hardness (of dry tablets) were found to be sensitive to the cross-linking degree (cld) variation. Best release proper ties and highest mechanical hardness were obtained from CLHAS matrices with low-to-moderate crystallinity, where the V- and the B-type structures coex ist with amorphous regions. X-ray and FTIR profiles of dry CLHAS powders we re found to be predictive for release properties of CLHAS tablets. (C) 2000 Elsevier Science S.A. All rights reserved.