EFFECT OF PAMAM SURFACE FUNCTIONAL GROUPS ON WATER SOLUBILITY IMPROVEMENT OF ALBENDAZOLE

E. SIGAL, L FERNANDEZ , J. J SILBER, M. SANTO

Los Cocos- Cba

Simposio; V Argentine-Chilean Polymer Symposium; 2009

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Albendazole (ABZ), methyl (5-[propylthio]-lHbenzimidazol-2-yl) carbamate is a broad spectrum antihelmintic agent than has been successfulIy used in clinic for the treatment of cerebral cysticercosis, (Zongde et al, 2005) and other helminthic parasites, such as pinworms, roundworms in the intestinal tract or tissues of the body. A major problem associated with the formulation and effectiveness of ABZ is its poor aqueous solubility, 0.61 µg/ml, which may account for its low and irregular bioavailability in humans. Previous studies shows than the complexation with povidone and ciclodextrines have been used to increase the solubility of ABZ and consequently improve its bioavailability, (Casulli et al, 2006). In the last years a novel polymeric nanoarchitectrue for solubility enhancement attracted the attention of many scientists. These new compounds, named dendrimers, have been tried successfulIy for enhancing the solubility of hydrophobes (Jang et al, 2009). The goal of this work was to examine the improvement of the aqueous solubility of ABZ using ethylenediamine core polyamidoamine (PAMAM) dendrimers as sohibility enhancers. In order to evaluate the capacity of this dendrirners for enhance the solubility of ABZ, UV absorption and fluorescence emission measurements of different ABZ-PAMAM systems were developed. The results obtained show than these polymeric structures have the capacity to enhance the solubility of ABZ. Drug-dendrimer association was attributed to hydrophobic effect and to hydrogen bond interaction. Although all dendrimer studied have hydrophobic nanocavity with similar dimensions, their surfaces differ significantly, causing that the nature and the localization of the interaction in ABZ-dendrimer association depended on the type of terminal groups.