PURPOSE: The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT(®) EPO (EPO) was investigated. METHODS: The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. RESULTS: Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state (1)H spin-lattice relaxation time (T(1)) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and (13)C-T(1) measurements. Solution-state (1)H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. (1)H-T(1) and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. CONCLUSIONS: The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO.
PURPOSE: The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT(®) EPO (EPO) was investigated. METHODS: The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. RESULTS: Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state (1)H spin-lattice relaxation time (T(1)) measurement showed that MFA was almost monomolecularly dispersed in the EPOpolymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and (13)C-T(1) measurements. Solution-state (1)H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. (1)H-T(1) and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. CONCLUSIONS: The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO.
Authors: Dwayne T Friesen; Ravi Shanker; Marshall Crew; Daniel T Smithey; W J Curatolo; J A S Nightingale Journal: Mol Pharm Date: 2008 Nov-Dec Impact factor: 4.939
Authors: Sultan M Alshehri; Jun-Bom Park; Bader B Alsulays; Roshan V Tiwari; Bjad Almutairy; Abdullah S Alshetaili; Joseph Morott; Sejal Shah; Vijay Kulkarni; Soumyajit Majumdar; Scott T Martin; Sanjay Mishra; Lijia Wang; Michael A Repka Journal: J Drug Deliv Sci Technol Date: 2015-06-01 Impact factor: 3.981
Authors: Abdullah S Alshetaili; Bjad K Almutairy; Roshan V Tiwari; Joseph T Morott; Sultan M Alshehri; Xin Feng; Bader B Alsulays; Jun-Bom Park; Feng Zhang; Michael A Repka Journal: Curr Drug Deliv Date: 2016 Impact factor: 2.565