Riisager, Ludmilla Lumholdt1; Holm, R.5; Jørgensen, E. B.5; Larsen, Kim Lambertsen3
1 Supramolekular Chemistry, The Faculty of Engineering and Science, Aalborg University, VBN2 Department of Chemistry and Bioscience, The Faculty of Engineering and Science, Aalborg University, VBN3 Section of Chemistry, The Faculty of Engineering and Science, Aalborg University, VBN4 The Faculty of Engineering and Science, Aalborg University, VBN5 Biologics and Pharmaceutical Science, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark
In vitro studies of α-amylase degradation of α-, β- and γ-cyclodextrins and 2-hydroxypropyl-β- and -γ-cyclodextrins were investigated spectrophotometrically by measuring the formation of reducing sugars, the reaction products of α-amylase degradation. This was done to evaluate potential degradation and thereby biological conversion of the cyclodextrins if dosed orally, as the intestinal tract contains α-amylase for digestive purposes. The results demonstrated that only γ- and 2-hydroxypropyl-γ-cyclodextrins can be degraded by α-amylase to a relevant extent, that is, γ- and 2-hydroxypropyl-γ-cyclodextrins have different biopharmaceutical behaviours than the other evaluated cyclodextrins. The rate of degradation was affected by the addition of the inclusion complex forming additives flurbiprofen, ibuprofen and benzo[a]pyrene. This effect between the degradation dynamics and the included additives was caused by a correlation between solubility of the additives and the stability of the complex.