Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal

In-depth studies on essential oil–based nanoemulsions (NEs) have centered on a variety of oral health issues. NEs improve the delivery of nonpolar active agents to sites and thereby boost the dissolution and distribution of the agents. Metronidazole-peppermint oil-tranexamic acid self-nanoemulsifying drug delivery systems (MZ-PO-TX-SNEDDS) were created and loaded into novel lozenges to act as antifungal, hemostatic, antimicrobial, and analgesic dosage forms after dental extractions. The design-of-experiments approach was used in creating them. To generate the NEs, different concentrations of MZ-PO (240, 180, and 120 mg), 2% TX (600, 450, and 300 mg), and Smix1:1 (600, 400, and 200 mg) were used. The ideal formulation had serum levels of 1530 U/mL of interleukin-6, a minimal inhibitory concentration against bacteria of 1.5 µg/mL, a droplet size of 96 nm, and a blood coagulation time of 16.5 min. Moreover, the produced NE offered better MZ release. The adopted design was used to produce the ideal formulation; it contained 240 mg of MZ-PO, 600 mg of 2% TX, and 600 mg of Smix1:1. It was incorporated into lozenges with acceptable characteristics and an improved capability for drug release. These lozenges had reasonable coagulation times, IL-6 serum levels, and MIC values. All of these characteristics are desirable for managing symptoms following tooth extractions. Therefore, these lozenges loaded with MZ-PO-TX-SNEDDs might be considered a beneficial paradigm for relieving complications encountered after tooth extractions.

2.1. Materials

The Amoun Company provided TX (El-Obour City, Cairo, Egypt). The MZ was a kind present from Bayer (Leverkusen, Germany). Tedia Corporation provided the following products: gelatin, hydroxypropyl cellulose, propylene glycol, oleic acid, carbopol, and PO (Fairfield, OH, USA). Gattefosse kindly donated Labrafac Lipophile WL 1349, polyglyceryl oleate, and Transcutol Plurol (Saint-Priest, France). Sigma-Aldrich provided Tween 80, Span 80, polyethylene glycol (PEG) 200, PEG 400, propylene glycol, glycerol, and ethanol (St. Louis, MO, USA). All additional chemicals and reagents were of normal analytical grades.

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Alissa, M.; Hjazi, A.; Abusalim, G.S.; Aloraini, G.S.; Alghamdi, S.A.; Rizg, W.Y.; Hosny, K.M.; Alblowi, J.A.; Alkharobi, H. Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal. Pharmaceutics 2023, 15, 2342.
https://doi.org/10.3390/pharmaceutics15092342

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