Characterization, inclusion mode, phase-solubility and in-vitro release studies of inclusion binary complexes with cyclodextrins and meglumine using sulfamerazine as model drug

C. ALOISIO; A. GOMES DE OLIVEIRA; M. LONGHI

DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY

TAYLOR & FRANCIS INC

Lugar: Austin, Texas; Año: 2014 vol. 40 p. 919 - 928

0363-9045

ABSTRACT In order to investigate the effect on the aqueous solubility and release rate of Sulfamerazine (SMR) as model drug, inclusion complexes with ß-cyclodextrin (ßCD), methyl-ß-cyclodextrin (MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) 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 were 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 uniozated drug. The best approach for SMR solubility enhancement result 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 ßCD, MßCD, 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 semi-permeable membranes.