Effects of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin on stability of ranitidine HCl

Abstract

Inclusion complexes of ranitidine HCI with β -cyclodextrin or 2-hydroxypropyl- β -cyclodextrin were prepared by means of co-grinding, freeze-drying and kneading techniques with three molar ratios (1:1, 1:2, and 2:1). Fourier-transform infrared spectra of both complex systems suggested that no strong chemical interaction was formed between the drug and cyclodextrins. However, differential scanning calorimetry thermograms indicated either the formation of inclusion complexes or the molecular dispersion of ranitidine HCI and cyclodextrin molecules. The 1:1 molar ratio of ranitidine HCI: Cyclodextrin was chosen for complex preparations. The freeze-drying method was chosen for preparing the inclusion complexes because the obtained products were inclusion complexes which were confirmed by proton nuclear magnetic resonance spectra, and gave the highest yield (= 90-95%). Both cyclodextrins did not change the degradation orders but changed the degradation rates of ranitidine HCI in all buffer solutions studied (pH 1, 3, 5, 7, 9,11, and 13). The degradation mechanisms were different at different pH values and could be grouped into three zones: at very low pH value (pH 1), at acidic pH values (pH 3 and 5), and at neutral to basic pH values (pH 7, 9, 11, and 13). The complexation with cyclodextrins, especially 2-hydroxypropyl-β-cyclodextrin, could stabilize ranitidine HCI except at pH 1 and 7. The critical relative humidity of ranitidine HCI powder in this study was around 73-76% relative humidity. Ranitidine HCI was unstable at % relative humidity above the critical relative humidity, but was stable at % relative humidity below the critical relative humidity. Both cyclodextrins also improved ranitidine HCI stability at % relative humidity above the critical relative humidity. However, ranitidine HCI:β-cyclodextrin complex was unstable around the critical relative humidity.