title: Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.
abstract: The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability.
authors.affiliation: Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy.
authors.forename: Natascia
authors.initials: N
authors.lastname: Mennini
authors.affiliation: Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maestrelli
authors.affiliation: Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Cirri
authors.affiliation: Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy. Electronic address: paola.mura@unifi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Mura
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001120:Arginine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D055598:Chemical Phenomena; D000077431:Oxaprozin; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D011422:Propionates / Q000737:chemistry*; D012995:Solubility; D014961:X-Ray Diffraction / Q000379:methods; D014965:X-Rays; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D019999:Pharmaceutical Solutions; D011208:Powders; D011422:Propionates; D047392:beta-Cyclodextrins; D001120:Arginine; D000077431:Oxaprozin
keywords: Arginine; Dissolution rate; Oxaprozin; Phase-solubility diagrams; Randomly-methylated ß-cyclodextrin; Ternary complexes