Enhancement of aqueous solubility of tricyclic acyclovir derivatives by their complexation with hydroxypropyl-β-cyclodextrin

Solubilities of tricyclic acyclovir derivatives in buffered aqueous solutions of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) at pH 5.5 and 7.0 were determined at 25 and 37 A degrees C. Complexation of these compounds with HP-beta-CD resulted in a noticeable increase of their solubility; nevertheless it was limited to tricyclic derivatives of acyclovir carrying an aryl substituent. Combination of H-1 NMR and DSC techniques demonstrated the existence of inclusion complexes between acyclovir derivatives and HP-beta-CD. The stability constants, estimated using the Higuchi-Connors method, were found in the range of 10-100 M-1. Additionally, the pK (a) values at 25 A degrees C and molar extinction coefficients in aqueous buffered solutions were also determined for all studied compounds.