title: Novel nanosized formulations of two diclofenac acid polymorphs to improve topical bioavailability.
abstract: In this work, nanocrystal formulations, containing two different diclofenac acid crystal forms, were developed with the aim to improve dermal drug bioavailability. Nanosuspensions were obtaining using wet media milling technique and were characterized in terms of size distribution, morphology, zeta potential, differential scanning calorimetry and X-ray powder diffractometry. The ability of the nanocrystals to improve dermal drug bioavailability was investigated in vitro using Franz diffusion vertical cells and newborn pig skin, in comparison with diclofenac acid coarse suspensions and a commercial topical formulation containing diclofenac sodium. Nanocrystals exhibited a mean diameter ranging between 279 and 315 nm and a PI lower than 0.25, as shown by PCS measurements. The XRDP and DSC analysis clearly indicated that the preparation process did not modify the diclofenac polymorphic forms. In vitro transdermal delivery experiments showed an improved skin deposition and permeation of the nanocrystals compared to coarse suspensions and diclofenac sodium commercial topical formulation. These results highlight the fundamental role of the crystal size on drug solubility and, thus, on the ability of a poorly soluble drug to cross the skin and accumulate in the deeper skin layers.
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Pireddu
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sinico
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, University of Cagliari and Unità di Ricerca del Consorzio Nazionale di Scienze e Tecnologie dei Materiali (INSTM), Cittadella Universitaria di Monserrato, SS 554 bivio Sestu, 09042 Monserrato, CA, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Ennas
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Marongiu
authors.affiliation: Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria, Edificio PolifunzionaleArcavacata di Rende, Cosenza, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Muzzalupo
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy. Electronic address: frlai@unica.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lai
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D033362:Powder Diffraction; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac
keywords: Crystal polymorphs; DSC; Dermal delivery; Diclofenac acid; Nanocrystals; Nanosuspension; XRD