title: Characterization, inclusion mode, phase-solubility and in vitro release studies of inclusion binary complexes with cyclodextrins and meglumine using sulfamerazine as model drug.
abstract: In order to investigate the effect on the aqueous solubility and release rate of sulfamerazine (SMR) as model drug, inclusion complexes with β-cyclodextrin (βCD), methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) and a binary system with meglumine (MEG) were developed. The formation of 1:1 inclusion complexes of SMR with the CDs and a SMR:MEG binary system in solution and in solid state was revealed by phase solubility studies (PSS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis and X-Ray diffractometry (XRD) studies. The CDs solubilization of SMR could be improved by ionization of the drug molecule through pH adjustments. The higher apparent stability constants of SMR:CDs complexes were obtained in pH 2.00, demonstrating that CDs present more affinity for the unionized drug. The best approach for SMR solubility enhancement results from the combination of MEG and pH adjustment, with a 34-fold increment and a Smax of 54.8 mg/ml. The permeability of the drug was reduced due to the presence of βCD, MβCD, HPβCD and MEG when used as solubilizers. The study then suggests interesting applications of CD or MEG complexes for modulating the release rate of SMR through semipermeable membranes.
authors.affiliation: Departamento de Farmacia, Facultad de Ciencias Químicas, UNITEFA (CONICET), Universidad Nacional de Córdoba, Ciudad Universitaria , X5000HUA Córdoba , Argentina and.
authors.forename: Carolina
authors.initials: C
authors.lastname: Aloisio
authors.forename: Anselmo
authors.initials: A
authors.lastname: Gomes de Oliveira
authors.forename: Marcela
authors.initials: M
authors.lastname: Longhi
mesh_terms: D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D008536:Meglumine / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013416:Sulfamerazine / Q000008:administration & dosage* / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; D008536:Meglumine; D013416:Sulfamerazine
keywords: Complexation; cyclodextrin; meglumine; permeability; sulfamerazine