Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation

Innovative formulations, including solid lipid nanoparticles (SLNs), have been sought to improve skin permeation of non-steroidal anti-inflammatory drugs (NSAIDs). The present study explores the use of SLNs, prepared using a fusion-emulsification method, to increase skin permeation and in vivo activity of two relevant NSAIDs: A liquid molecule (etofenamate) and a solid one (ibuprofen), formulated in a 2% hydroxypropyl methylcellulose gel through the gelation of SLN suspensions. Compritol^® 888 ATO and Tween^®80 were used as a solid lipid and a surfactant, respectively. All production steps were up scalable, resulting in SLNs with high encapsulation efficiency (>90%), a mean particle size of <250 nm, a polydispersity index <0.2, and that were stable for 12 months. In vitro permeation, using human skin in Franz diffusion cells, showed increased permeation and similar cell viability in Df and HaCaT cell lines for SLN formulations when compared to commercial formulations of etofenamate (Reumon^® Gel 5%) and ibuprofen (Ozonol^® 5%). In vivo activity in the rat paw edema inflammation model showed that SLN hydrogels containing lower doses of etofenamate (8.3 times lower) and ibuprofen (16.6 times lower) produced similar effects compared to the commercial formulations, while decreasing edema and inflammatory cell infiltration, and causing no histological changes in the epidermis. These studies demonstrate that encapsulation in SLNs associated to a suitable hydrogel is a promising technological approach to NSAIDs dermal application.

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or continue reading here: Mancini, G.; Gonçalves, L.M.D.; Marto, J.; Carvalho, F.A.; Simões, S.; Ribeiro, H.M.; Almeida, A.J. Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation. Pharmaceutics 2021, 13, 328. https://doi.org/10.3390/pharmaceutics13030328

Conclusions
The work essentially addressed the pharmaceutical and preclinical development of improved topical NSAID‐containing formulations consisting of etofenamate and ibuprofen encapsulated in SLNs. Nanoparticle suspensions were then gelated to produce hydrogels suitable for dermal application. All preparation procedures were up scalable and resulted in physically and microbiologically stable formulations. The solid lipid and emulsifying agent, Compritol® 888 ATO and Tween® 80, respectively, resulted in SLN formulations with suitable particle size (<250 nm), encapsulation efficiency (>90%), and stability (12 months). The SLN‐containing hydrogels increased drug permeation when comparing etofenamate and ibuprofen hydrogel commercial hydrogel formulations (Reumon® Gel 5% and Ozonol® 5%, respectively). In vivo studies using the rat paw edema inflammation model showed that hydrogels containing lower doses of etofenamate (8.3 times lower) and ibuprofen (16.6 times lower) formulated in SLN produced a similar antiinflammatory effect, compared to the commercial reference products, with no histological changes in the epidermis and a significant decrease in edema and inflammatory cell infiltration. These studies demonstrate that encapsulation in SLNs associated to a suitable hydrogel is a promising, straightforward technological approach to NSAIDs dermal application. Further optimization studies on SLN physicochemical characteristics, hydrogel rheological behavior, and scale‐up are currently being performed.