title: The effect of beta-cyclodextrins on the permeation of diclofenac from supersaturated solutions.
abstract: Supersaturation is a very useful method of enhancing the permeation of drugs across membranes such as skin, because unlike other methods, it does not interfere with the ultrastructure of the stratum corneum. Many drugs are able to form inclusion complexes with beta-cyclodextrins (beta-CDs) and this study investigates the anti-nucleating effects of these compounds on supersaturated solutions of diclofenac. The ability of various betaCDs to form inclusion complexes with diclofenac was assessed by measuring their saturated solubilities. Solutions containing hydroxypropyl beta-cyclodextrin (HPbeta-CD, with a molar substitution of 0.9) produced a 7.5-fold increase in the solubility of diclofenac, which suggested that a strong complex was formed between the two compounds. This association was characterized using differential scanning calorimetry. Permeation across silicone membranes of these saturated solutions of diclofenac in the presence of the different betaCDs produced similar flux values suggesting that the overall activity was also similar. The effect of different molar ratios of HPbeta-CD and diclofenac, and the anti-nucleating effect of HPbeta-CD (both on its own and in combination with a known anti-nucleant, hydroxypropylmethyl cellulose (HPMC)) on the diffusion of diclofenac across silicone membranes was investigated. HPbeta-CD appears to have a stabilizing effect on supersaturated solutions of diclofenac as a co-ingredient with HPMC.
authors.affiliation: Faculdade de Farmácia, Universidade de Lisboa, Av. das Forças Armardas, 1600 Lisboa, Portugal.
authors.forename: M M R
authors.initials: MM
authors.lastname: Dias
authors.forename: S L
authors.initials: SL
authors.lastname: Raghavan
authors.forename: M A
authors.initials: MA
authors.lastname: Pellett
authors.forename: J
authors.initials: J
authors.lastname: Hadgraft
mesh_terms: D003505:Cyclodextrins / Q000032:analysis / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000032:analysis / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000493:pharmacokinetics; D012995:Solubility / Q000187:drug effects; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D019999:Pharmaceutical Solutions; D047392:beta-Cyclodextrins; D004008:Diclofenac; C031215:betadex