title: Triamcinolone solubilization by (2-hydroxypropyl)-β-cyclodextrin: A spectroscopic and computational approach.
abstract: The molecular foundations of the use of (2-hydroxypropyl)-β-cyclodextrin (HPβCD) as solubility promoter of triamcinolone acetonide (TrA), a corticosteroid with very low aqueous solubility, was investigated by a multidisciplinary spectroscopic and computational approach. Aqueous solutions of TrA and HPβCD were investigated by UV and NMR spectroscopies. The association constant was determined by phase solubility diagrams and by the Foster-Fyfe method whereas the nature of the drug/cyclodextrin aggregates was probed by using the NMR DOSY technique. ROE measurements in solution led to stereochemical information regarding the nature of inclusion processes. TrA/HPβCD powders were prepared and investigated by Raman spectroscopy supported by computational methods. A molecular interaction of the hydroxyacyl chain with cyclodextrin, not identified in solution, was detected. Raman imaging experiments confirmed the attainment of a molecularly homogeneous system when the TrA/HPβCD molar ratio was 1:7 whereas TrA crystallized for mixtures richer in TrA (1:3.5) forming domains with size in the range of 10-15μm. We demonstrate that the combined use of several spectroscopical techniques with specific responsivities allows a detailed depiction of drug/cyclodextrin interaction useful in the development of novel pharmaceutical formulation.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Miro
authors.forename: Francesca
authors.initials: F
authors.lastname: Ungaro
authors.forename: Federica
authors.initials: F
authors.lastname: Balzano
authors.forename: Sofia
authors.initials: S
authors.lastname: Masi
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Pietro
authors.initials: P
authors.lastname: La Manna
authors.forename: Gloria
authors.initials: G
authors.lastname: Uccello-Barretta
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quaglia
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002236:Carbohydrate Conformation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D014222:Triamcinolone Acetonide / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014222:Triamcinolone Acetonide