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  • Title: Comparison of the aqueous solubilization of practically insoluble niclosamide by polyamidoamine (PAMAM) dendrimers and cyclodextrins.
    Author: Devarakonda B, Hill RA, Liebenberg W, Brits M, de Villiers MM.
    Journal: Int J Pharm; 2005 Nov 04; 304(1-2):193-209. PubMed ID: 16198076.
    Abstract:
    This study is the first report of the solubilization of niclosamide by cyclodextrin complexation or the interaction between the drug and polyamidoamine (PAMAM) dendrimers. Half generation dendrimers with more polar carboxylate surface functional groups did not increase the solubility of niclosamide. From the phase solubility studies, when the fold enhancement in solubility of niclosamide combined with full generation amine terminated PAMAM dendrimers was compared with that obtained when the drug was combined with beta- or hydroxypropyl-beta-cyclodextrin, the results showed that, except for G-0 dendrimer at pH 7, the solubility of niclosamide was significantly higher in the presence of the dendrimers. In addition, higher equilibrium stability constants and complexation efficiency showed that the dendrimers formed stronger more stable complexes than the CDs. However, the strong interaction between the amine surface functional groups and the niclosamide molecule complexes caused a decrease in dissolution rate compared to the CDs because the interaction retarded the release of the drug from the dendrimers. In addition to increasing the solubility, PAMAM dendrimers therefore also offer the possible for the controlled release of the drug from solid dosage forms.
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