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 cross-linking, was recently introduced as an excipient (Contramid) for monolithic dosage forms that are able to control drug release over 18-24 h. These control properties are related to tablet swelling and are strongly dependent on the degree of the cross-linking of CLHAS. The permeability of solutes through CLHAS hydrogels depends on the chemical structure of the polymer. The aim of this study was to obtain a better understanding of how modifications in CLHAS molecular structures at the level of long-range and short-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 aspects of starch products. X-ray diffractometry, FTIR spectroscopy, dissolution tests in vitro, and mechanical hardness (of dry tablets) were found to be sensitive to the cross-linking degree (cld) variation. Best release properties and highest mechanical hardness were obtained from CLHAS matrices with low-to-moderate crystallinity, where the V- and the B-type structures coexist with amorphous regions. X-ray and FTIR profiles of dry CLHAS powders were found to be predictive for release properties of CLHAS tablets.
Ispas-Szabo
P
P
Department of Chemistry-Biochemistry, Université du Québec à Montréal, Canada.
Ravenelle
F
F
Hassan
I
I
Preda
M
M
Mateescu
M A
MA
D000688:Amylose / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003692:Delayed-Action Preparations; D007700:Kinetics; D008962:Models, Theoretical; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013997:Time Factors; D014961:X-Ray Diffraction
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D000688:Amylose