title: Surfactant choice and the physical stability of nanosuspensions as a function of pH.
abstract: Nanosuspensions of the example compounds ketoconazole and itraconazole were shown to aggregate upon reducing the pH to levels comparable to that known to exist in the stomach. Manipulation of the surfactant/polymer ratio in the suspension vehicle did not elucidate the cause of the aggregation. X-ray diffraction on ketoconazole solids failed to identify a form change as causative. Ultimately, ketoconazole intrinsic dissolution rate experiments implicated surface salt formation between ketoconazole and the vehicle surfactant as the cause of the aggregation. The generality of the phenomenon is discussed.
authors.affiliation: Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Donoso
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Haskell
authors.forename: Richard R
authors.initials: RR
authors.lastname: Schartman
mesh_terms: D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005665:Furosemide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D017964:Itraconazole / Q000737:chemistry*; D007654:Ketoconazole / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010894:Piroxicam / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013535:Suspensions
chemical_list: D013501:Surface-Active Agents; D013535:Suspensions; D004143:Dioctyl Sulfosuccinic Acid; D010894:Piroxicam; D017964:Itraconazole; D005665:Furosemide; D011205:Povidone; D007654:Ketoconazole