TY - JOUR

T1 - Investigation of diclofenac release and dynamic structural behavior of non-lamellar liquid crystal formulations during in situ formation by UV–Vis imaging and SAXS

AU - Mertz, Nina

AU - Bock, Frederik

AU - Østergaard, Jesper

AU - Yaghmur, Anan

AU - Weng Larsen, Susan

N1 - Funding Information: Nina Mertz acknowledge support from the Brødrene Hartmann Foundation (Copenhagen, Denmark), application A31173. SAXS beamtime at the synchrotron light source ELETTRA (Trieste, Italy) was provided under the proposal 20182095 and funded by the Central European Research Infrastructure Consortium (CERIC). The authors wish to extend their gratitude for efficient assistance of Heinz Amenitsch (Institute of Inorganic Chemistry, Graz University of Technology, Graz, Austria) and Gizem Bor (Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen) during the SAXS experiments. Funding Information: Nina Mertz acknowledge support from the Brødrene Hartmann Foundation (Copenhagen, Denmark), application A31173. SAXS beamtime at the synchrotron light source ELETTRA (Trieste, Italy) was provided under the proposal 20182095 and funded by the Central European Research Infrastructure Consortium (CERIC). The authors wish to extend their gratitude for efficient assistance of Heinz Amenitsch (Institute of Inorganic Chemistry, Graz University of Technology, Graz, Austria) and Gizem Bor (Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen) during the SAXS experiments. Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - In situ formation of high viscous inverse lyotropic non-lamellar liquid crystalline phases is a promising approach for sustained drug delivery in the joint. The in situ forming process on exposure of two diclofenac-loaded preformulations to aqueous media was characterized with respect to depot size and shape, initial release and structural transitions using UV–Vis imaging and spatially and time-resolved synchrotron small-angle X-ray scattering (SAXS). The preformulations consisted of 10 % (w/w) ethanol, 10 % (w/w) water and a binary lipid mixture of glycerol monooleate (GMO):1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DOPG) or GMO:medium chain triglycerides (MCT). Upon injection of preformulations into an employed injection-cell containing excess of bio-relevant medium, rapid generation of liquid crystalline depots was observed. UV–Vis images and constructed 2D SAXS maps of the injection-cell showed depots with different shapes and sizes, and features with high nanostructural heterogeneity. More extensive swelling of the GMO:DOPG-based preformulation was observed compared to the GMO:MCT-based preformulation. The UV image analysis found that a higher amount of diclofenac was released in the image area after 20 h from the GMO:MCT depot compared to the GMO:DOPG depot. The injection-cell setup employing UV–Vis imaging and synchrotron SAXS constitutes an attractive approach for evaluating the in situ forming processes of liquid crystalline depots.

AB - In situ formation of high viscous inverse lyotropic non-lamellar liquid crystalline phases is a promising approach for sustained drug delivery in the joint. The in situ forming process on exposure of two diclofenac-loaded preformulations to aqueous media was characterized with respect to depot size and shape, initial release and structural transitions using UV–Vis imaging and spatially and time-resolved synchrotron small-angle X-ray scattering (SAXS). The preformulations consisted of 10 % (w/w) ethanol, 10 % (w/w) water and a binary lipid mixture of glycerol monooleate (GMO):1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DOPG) or GMO:medium chain triglycerides (MCT). Upon injection of preformulations into an employed injection-cell containing excess of bio-relevant medium, rapid generation of liquid crystalline depots was observed. UV–Vis images and constructed 2D SAXS maps of the injection-cell showed depots with different shapes and sizes, and features with high nanostructural heterogeneity. More extensive swelling of the GMO:DOPG-based preformulation was observed compared to the GMO:MCT-based preformulation. The UV image analysis found that a higher amount of diclofenac was released in the image area after 20 h from the GMO:MCT depot compared to the GMO:DOPG depot. The injection-cell setup employing UV–Vis imaging and synchrotron SAXS constitutes an attractive approach for evaluating the in situ forming processes of liquid crystalline depots.

KW - In vitro release testing

KW - Intra-articular administration

KW - Non-lamellar liquid crystalline phases

KW - Swelling behavior

KW - time-resolved SAXS

KW - UV–Vis imaging

U2 - 10.1016/j.ijpharm.2022.121880

DO - 10.1016/j.ijpharm.2022.121880

M3 - Journal article

C2 - 35661744

AN - SCOPUS:85131590479

VL - 623

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 121880

ER -