title: On the correlation between the structure of lyotropic carriers and the delivery profiles of two common NSAIDs.
abstract: Two non-steroidal anti-inflammatory drugs (NSAIDs), sodium diclofenac (Na-DFC) and celecoxib (CLXB) were solubilized within cubic and lamellar mesophases as carriers for transdermal drug delivery. SD-NMR, SAXS, ATR-FTIR, and EPR measurements were performed to examine the systems' characteristics and the interactions between the drugs and their hosting mesophases. The amphiphilic drug Na-DFC was found to incorporate at the interfaces of the cubic and lamellar mesophases and thus to act as a cosurfactant and a "structure stabilizer". It increased the order degree and the interactions between the GMO molecules and led the systems toward denser packing. CLXB exhibits an opposite effect on the mesophases. Its solubilization within both systems is accompanied with significant channel swelling and decrease in the order degree. The hydrophobic, rigid and bulky CLXB behaves as a "structure breaker", incorporated between the GMO tails, disturbing the mesophase packing and enhancing the repulsion at the tails region, limiting their close binding. Release experiments from Franz cells revealed that Na-DFC release is dependent on the quantity of water within the hosting mesophase as the water-rich formulation exhibits 1.5-fold enhancement in the release of the drug, compared to the lamellar phase. In contrast, CLXB release was not influenced by the water quantity, hinting that the release mechanisms of the drugs are different while Na-DFC diffuses from the water channels to the external phase, CLXB diffusion occurs through the continuous lipophilic region. The difference in the solubilization sites and interactions of each drug with the mesophases affect their release profiles and determine the preferred formulations for each drug's delivery vehicle.
authors.affiliation: Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Marganit
authors.initials: M
authors.lastname: Cohen-Avrahami
authors.affiliation: Department of Physics, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Shames
authors.affiliation: Department of Earth, Life and Environment Sciences, University of Urbino, Loc. Crocicchia, Urbino 61029, Italy.
authors.forename: M Francesca
authors.initials: MF
authors.lastname: Ottaviani
authors.affiliation: Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aserin
authors.affiliation: Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel. Electronic address: garti@vms.huji.ac.il.
authors.forename: Nissim
authors.initials: N
authors.lastname: Garti
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004337:Drug Carriers; D004578:Electron Spin Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D053838:Scattering, Small Angle; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers
keywords: ATR-FTIR; EPR; Liquid crystals; NSAID; SAXS; Transdermal drug delivery