Preformulation of an oral cyclosporine free of su

Authors: Taher Boukhris Malika LahianiSkiba Damien Martin Mohamed Skiba

Publish Date: 2012/06/20

Volume: 75, Issue: 3-4, Pages: 323-332

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Abstract

The purpose of this study was to develop a new oral cyclosporine A CsA formulation free of surfactant cremophor using cyclodextrin terpolymers PαβCD PβγCD and PαγCD as excipients in attempt to enhance its stability dissolution rate and eliminate surfactant side effects Two spraydried dispersions SDDs containing poorly watersoluble CsA were prepared with either PαβCD PβγCD or PαγCD using water F textH 2 textO and ethanol F EOH via spraydrying technique and characterized by scanning electron microscopy powder Xray diffraction particle size distribution circular dichroism CD and nuclear magnetic resonance along with the dissolution study which was compared to Neoral® and Sandimmune® The results showed an interaction between CsA and PαβCD PβγCD and PαγCD without secondary structure change of CsA The order of the CsA release from the terpolymers was ranked as follows PαγCD/CsA F textH 2 textO  = Neoral®  PβγCD/CsA F textH 2 textO   PαβCD/CsA F textH 2 textO   PαγCD/CsA F EOH  Sandimmune®  PαβCD/CsA F EOH  PβγCD/CsA F EOH The results of F textH 2 textO could be explained by hydrophilisation and absence of crystallinity of CsA while maintaining part of its crystallinity in the case of formulations F EOH In summary developed SDD formulations PαγCD/CsA F textH 2 textO revealed same dissolution profile as Neoral® and better than Sandimmune® These systems seem to be stable to carry cyclosporine and release it while preserving structure and thus potentially also maintaining cyclosporine activity

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