Journal
CARBOHYDRATE POLYMERS
Volume 87, Issue 1, Pages 512-517Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2011.08.010
Keywords
Loratadine; beta-CD; HP-beta-CD; Inclusion complex; Mechanical grinding; Inclusion steps; Thermodynamic kinetics; Inclusion efficiency; Crystallinity; Amorphization
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The interaction of poor water-soluble drug loratadine (LOR) with beta-cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous or solid state was investigated. Mechanical grinding effect on the inclusion steps, thermodynamic kinetics and inclusion efficiency of inclusion complex formation of LOR with beta-CD or HP-beta-CD was quantitatively investigated by DSC and FT-IR microspectroscopy with curve-fitting analysis. The phase solubility profiles of LOR with beta-CD and HP-beta-CD were classified as A(L)-type phase diagram. The grinding-induced reduction in LOR crystallinity in the presence of beta-CD or HP-beta-CD was found to be apparent zero-order kinetics. The inclusion efficiency of solid inclusion complex for LOR/beta-CD or LOR/HP-beta-CD was significantly correlated with the reduction in LOR crystallinity and the grinding time. The mechanism of inclusion complex formation for LOR/beta-CD or LOR/HP-beta-CD was proposed through the progressive reduction in LOR crystallinity, the promoted LOR amorphization, and molecular inclusion processes in the continuous energy input process of mechanical grinding. (C) 2011 Elsevier Ltd. All rights reserved.
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