Anion effects on electrostatic charging of sterically stabilized, water insoluble drug particles

Water-insoluble suspensions of itraconazole and budesonide were sterically stabilized using nonionic polymers (poloxamer 188 or polysorbate 80) and probed for polymer-anion interactions by measuring changes in particle zeta potential. Anions comprising a range of functionalities and aqueous solubilities were examined. Results showed that the more hydrophobic anions partitioned to the particle interface, and a simple model for predicting anion adsorption was developed from their calculated properties. Anions with a calculated Klopman water solubility less than 10 mu M ora calculated log P > 3.5 were adsorbed to the particle-polymer interface effectively increasing the overall particle charge. Anions of similar hydrophobicities with sulfonate or sulfate functionalities showed a much higher degree of particle charging compared with their carboxylate and phosphonate analogs at pH 9.5. In addition, the electrostatic charging of particles occurred at lower solution concentrations of sulfonate derivatives. These results suggest that the relative basicity of the oxoanion functionality may influence protonation or ion-pairing phenomena of the anions when adsorbed at the particle-polymer interface. Cetyltetramethylammonium bromide (CTAB) produced a positively charged particle consistent with the model developed for anion adsorption. Particle charging of sterically stabilized drug suspensions appeared largely independent of drug and polymer type. Anion hydrophobicity (solubility) and headgroup functionality dictated the observed charging behavior. (C) 2008 Elsevier B.V. All rights reserved.