Effect of pH on Solubilisation of Practically Insoluble Sorafenib by Classic and Stealth Polyamidoamine (PAMAM) Dendrimers and β-Cyclodextrin

This study is the first report of the solubilization of sorafenib (SFB), a water insoluble drug, by polyamidoamine (PAMAM) dendrimers and β-cyclodextrin (β-CD). For this study whole generations (G4 and G5) of PAMAM dendrimers have been used. The aqueous solubility of sorafenib was measured in the presence of dendrimers and β-cyclodextin at 30 C at pH 4, 7.4, and 10 using the Higuchi rotating bottle method. The amount of solubilized SFB was measured by HPLC-UV method. FTIR and UV-Vis spectroscopy were used to confirm complexation. From the phase solubility studies, it was found that PAMAM dendrimers increased SFB solubility most in pH 4. The maximum solubilizing effect was for G4 PAMAM dendrimers at pH 4 up to 36 folds. β-CD did not or slightly increased the solubility of SFB.