Complexation study of the anticancer agent EO-9 with 2-hydroxypropyl-beta-cyclodextrin

J.H. Beijnen, S.C. van der Schoot, B. Nuijen, F.M. Flesch, A. Gore, D Mirejovsky, L Lenaz

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For the development of a bladder instillation of the indoloquinone agent EO-9, use of the complexing agent 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) was considered. Therefore, a complexation study of EO-9 with HP beta CD was performed. Complexation was studied in aqueous solution and in solid freeze-dried products. A phase solubility study, UV-visible spectroscopy (UV/VIS), and analysis of the effect of HP beta D on the stability of EO-9 were performed. With the phase solubility study, a complexation constant (K1:1) of 32.9, a complexation efficiency (CE) of 0.0457, and a utility number (UCD) of 38.3 were calculated. These K1:1 and CE values indicate a weak complex, but the UCD shows that HP beta CD can be very useful as solubilizer in the desired formulation. Furthermore, a positive effect of HP beta CD on the chemical stability of EO-9 in solution was seen. Subsequently, complexation in the freeze-dried products was studied more thoroughly using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses. HP beta CD was found to be an excellent pharmaceutical complexing agent for application in formulations for EO-9 bladder instillations. Reconstitution before use of the developed freeze-dried products can be simply accomplished with water for injection.
Original languageUndefined/Unknown
Pages (from-to)1130-1139
Number of pages10
JournalDrug Development and Industrial Pharmacy
Issue number10
Publication statusPublished - 2008

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