title: Polypropylene imine dendrimer mediated solubility enhancement: effect of pH and functional groups of hydrophobes.
abstract: Dendrimers today are known for their three dimensional, monodispersed, highly branched, macromolecular nano-scopic architecture with number of reactive end groups. Dendrimers have been reported to act as solubilizing agents to host both hydrophilic and hydrophobic drugs. The present study was performed to investigate the effect of pH on poly(propylene) imine dendrimers (5.0G) mediated solubility enhancement of hydrophobes differing in functional groups (pKa). Weakly basic, (famotidine, -NH2 functional group; pKa 7.1), weakly acidic (indomethacin, -COOH functional group; pKa 4.5) and amphoteric (amphotericin B, -COOH and -NH2 functional groups; pKa 5.7 and 10.0) hydrophobes were selected for the study. The experiment was carried out at pH 4.0, 7.4 and 10.0. The solubility of all the drugs was enhanced at pH 7.4 and 10.0 but not at pH 4.0. The drug-dendrimer complexes followed 1:1 stoichiometry (AL type of curve) and were characterized for stability of complex, complexation efficiency and thermodynamic properties. Thermodynamic properties were utilized to elucidate the mechanism behind dendrimer mediated solubility enhancement. The data suggested that hydrophobic and electrostatic interactions were responsible for solubility enhancement. Conclusively, PPI dendrimers were found useful in solubility enhancement of not only acidic and basic but also amphoteric drugs, their solubilization ability was clearly regulated by pH and chemical nature of drug.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470 003, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Gupta
authors.forename: Hrushikesh Bharat
authors.initials: HB
authors.lastname: Agashe
authors.forename: Narendra Kumar
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000666:Amphotericin B / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D004355:Drug Stability; D015738:Famotidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry; D012995:Solubility; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D050091:Dendrimers; D011126:Polypropylenes; C443641:poly(propyleneimine); D015738:Famotidine; D000666:Amphotericin B; D007213:Indomethacin