Abstract
Purpose: To formulate Eudragit RS 100-based nanoparticles containing metronidazole (MTZ NPs) and incorporate them into hydrogels using different gelling agents for controlled release in the buccal mucosa.
 Method: MTZ NPs were fabricated using the nanoprecipitation method. MTZ NPs (1 % w/w) were introduced into hydrogels using different gelling excipients. Physicochemical properties of MTZ NPs, mucoadhesive strength and spreadability of the hydrogels, and ex vivo permeation of MTZ were evaluated.
 Results: MTZ NPs were spherical in shape and had a mean particle size of 201.9 ± 5.6 nm, polydispersity index (PDI) of 0.092 ± 0.014, and encapsulation efficiency of 46.28 ± 1.18 %. Hydroxyethyl cellulose (HEC) hydrogel containing MTZ NPs showed homogenous and smooth appearance, mucoadhesive strength of 2789.7 ± 13.4 dyne/cm2 , and spreadability of 5.32 ± 0.77 cm. The cumulative amount of drug permeated from MTZ hydrogel and MTZ-containing NP hydrogel through porcine buccal mucosa was 1104.33 ± 28.97 and 397.62 ± 16.13 µg/cm2 , respectively, after 7 h (p < 0.05).
 Conclusion: HEC hydrogel containing MTZ NPs demonstrates high mucoadhesive strength, good spreadability, and sustained ex vivo permeation of MTZ. Thus, HEC hydrogel is a promising pharmaceutical formulation for controlled drug release in the buccal mucosa
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