title: Supramolecular organization and release properties of phospholipid-hyaluronan microparticles encapsulating dexamethasone.
abstract: We describe the supramolecular organization of hybrid microparticles encapsulating dexamethasone (DXM) prepared by spray drying 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and hyaluronic acid (HA). The effect of DXM concentration on size distribution and encapsulation efficacy was evaluated as a function of HA concentration. In the absence of HA, DXM leads to a strong particle aggregation, whereas in the presence of HA, the aggregation is practically suppressed. DXM percentage of encapsulation is high (95+/-6%), independently of composition. Drug-excipient interactions were analyzed by differential scanning calorimetry (DSC) and X-ray diffraction. DSC demonstrates that only a small fraction of DXM interacts with DPPC, whereas X-ray diffraction does not detect this interaction. Finally, in vitro release studies show that HA does not influence DXM release kinetics. In all cases, a burst release of DXM is observed during the first hour. Under sink conditions, powder concentration in the release medium governs the extent of the burst. Under non sink conditions, DXM release is mostly governed by DXM solubility in the release medium. In the dry microparticles, DXM is probably mostly in amorphous domains within the DPPC-HA matrix. Upon hydration, the majority of the drug is released and only a small amount of DXM interacts with DPPC.
authors.affiliation: Faculté de Pharmacie, Univ Paris Sud, 5 Rue Jean-Baptiste Clement, Châtenay-Malabry, France.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gómez-Gaete
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.forename: Lídia
authors.initials: L
authors.lastname: Silva
authors.forename: Claudie
authors.initials: C
authors.lastname: Bourgaux
authors.forename: Madeleine
authors.initials: M
authors.lastname: Besnard
authors.forename: Amélie
authors.initials: A
authors.lastname: Bochot
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003907:Dexamethasone / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D006820:Hyaluronic Acid / Q000737:chemistry*; D007700:Kinetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D011208:Powders; D015060:1,2-Dipalmitoylphosphatidylcholine; D003907:Dexamethasone; D006820:Hyaluronic Acid