Biopharmaceutical profile of hydrogels containing pranoprofen-loaded PLGA nanoparticles for skin administration: In vitro, ex vivo and in vivo characterization.

Pranoprofen (PF)-loaded nanoparticles (PF-F1NPs and PF-F2NPs) have been formulated into blank hydrogels (HG_PF-F1NPs and HG_PF-F1NPs) or into hydrogels composed of 3% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone), as innovative strategy to improve the biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (Pranoprofen, PF) for topical application. The purpose of this approach has been to increase the contact of PF with the skin, improve its retention in deeper layers, thus enhancing its anti-inflammatory and analgesic effects. The physicochemical characterization of the developed hydrogels showed a non-Newtonian behaviour, typical of semi-solid formulations for skin administration, with sustained release profile. The results obtained from ex vivo skin human permeation and in vivo anti-inflammatory efficacy studies suggest that topical application of HG_PF-F2NPs has been more effective in the treatment of oedema on the skin' surface in comparison to other hydrogels. No signs of skin irritancy have been detected for all the semi-solid formulations containing 0% or 3% azone.

Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.

Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels.

Validated spectrofluorometric method for determination of gemfibrozil in self nanoemulsifying drug delivery systems (SNEDDS).

A spectrofluorometric method has been developed and validated for the determination of gemfibrozil. The method is based on the excitation and emission capacities of gemfibrozil with excitation and emission wavelengths of 276 and 304 nm respectively. This method allows de determination of the drug in a self-nanoemulsifying drug delivery system (SNEDDS) for improve its intestinal absorption. Results obtained showed linear relationships with good correlation coefficients (r(2)>0.999) and low limits of detection and quantification (LOD of 0.075 µg mL(-1) and LOQ of 0.226 µg mL(-1)) in the range of 0.2-5 µg mL(-1), equally this method showed a good robustness and stability. Thus the amounts of gemfibrozil released from SNEDDS contained in gastro resistant hard gelatine capsules were analysed, and release studies could be performed satisfactorily.

Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil.

Self-nanoemulsifying drug delivery systems of gemfibrozil were developed under Quality by Design approach for improvement of dissolution and oral absorption. Preliminary screening was performed to select proper components combination. Box-Behnken experimental design was employed as statistical tool to optimize the formulation variables, X(1) (Cremophor(®) EL), X(2) (Capmul(®) MCM-C8), and X(3) (lemon essential oil). Systems were assessed for visual characteristics (emulsification efficacy), turbidity, droplet size, polydispersity index and drug release. Different pH media were also assayed for optimization. Following optimization, the values of formulation components (X(1), X(2), and X(3)) were 32.43%, 29.73% and 21.62%, respectively (16.22% of gemfibrozil). Transmission electron microscopy demonstrated spherical droplet morphology. SNEEDS release study was compared to commercial tablets. Optimized SNEDDS formulation of gemfibrozil showed a significant increase in dissolution rate compared to conventional tablets. Both formulations followed Weibull mathematical model release with a significant difference in t(d) parameter in favor of the SNEDDS. Equally amodelistic parameters were calculated being the dissolution efficiency significantly higher for SNEDDS, confirming that the developed SNEDDS formulation was superior to commercial formulation with respect to in vitro dissolution profile. This paper provides an overview of the SNEDDS of the gemfibrozil as a promising alternative to improve oral absorption.