title: Solubilization of gabapentin into HII mesophases.
abstract: In the present work, we report on the solubilization of gabapentin (GBP) into lyotropic hexagonal mesophases composed of monoolein, tricaprylin, and water. It was demonstrated that the hexagonal structure remained intact up to 2 wt % gabapentin, whereas the lamellar phase coexisted with the hexagonal one in the concentration range of 3-4 wt % of the drug. At gabapentin content of 5-6 wt %, only lamellar phases containing defects such as dislocations and multilamellar vesicles were detected. Incorporation of GBP decreased the lattice parameter of the H(II) mesophase from 56.6 to 50.6 Å, while the structural dimensions of the lamellar phase were not affected. ATR-FTIR analysis suggested enhanced hydrogen bonding between the protonated amine of GBP and the O-H groups of the GMO and the water surrounding in the inner hydrophilic interface region. This led to intercalation of the drug into the water-lipid interface. At higher GBP loads of 4-6 wt %, thermal analysis revealed disordering within the lipid packing, apparently induced by the spatially altered interface area. Rheological measurements correlated the macroscopic features of the systems with alterations on the molecular level and allowed distinguishing between closely related mesophases due to their different rheological characteristics. In vitro transdermal delivery studies showed that the examined mesophases enabled a sustained release of GBP compared to its aqueous solution. Sustained release was more pronounced in the case of the hexagonal mesophase, compared to the lamellar one.
authors.affiliation: Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Achrai
authors.forename: Dima
authors.initials: D
authors.lastname: Libster
authors.forename: Abraham
authors.initials: A
authors.lastname: Aserin
authors.forename: Nissim
authors.initials: N
authors.lastname: Garti
mesh_terms: D000588:Amines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002210:Caprylates / Q000737:chemistry; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D000077206:Gabapentin; D005989:Glycerides / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D053838:Scattering, Small Angle; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry; D014867:Water / Q000737:chemistry; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*
chemical_list: D000588:Amines; D002210:Caprylates; D003509:Cyclohexanecarboxylic Acids; D005989:Glycerides; D013501:Surface-Active Agents; D014280:Triglycerides; D014867:Water; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; C003637:tricaprylin; C005953:monoolein