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. 2023 Sep 19;15(9):2342.
doi: 10.3390/pharmaceutics15092342.

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

Mohammed Alissa  1 , Ahmed Hjazi  1 , Ghadah S Abusalim  1 , Ghfren S Aloraini  1 , Suad A Alghamdi  1 , Waleed Y Rizg  2   3 , Khaled M Hosny  2   4 , Jazia A Alblowi  5 , Hanaa Alkharobi  6
Affiliations

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

Mohammed Alissa et al. Pharmaceutics. .

Abstract

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.

Keywords: hemostatic; lozenges; metronidazole; nanoemulsion; optimization; peppermint oil; periodontitis; tooth extraction; tranexamic acid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of metronidazole (A) and tranexamic acid (B).
Figure 2
Figure 2
The pseudoternary phase diagram of the MZ-PO phase, 2% TX-aqueous phase, and Smix.
Figure 3
Figure 3
Measured solubility of MZ in different cosurfactants (means ± SD, n = 3).
Figure 4
Figure 4
Effects of different independent elements on the droplet size of various MZ-PO-TX-NEs as shown by (A) Perturbation plot, (B) contour plot, and (C) 3D surface plot showing the; effects of different independent elements on the blood coagulation time in rats after administration of various MZ-PO-TX-NEs as presented by (D) Perturbation plot, (E) contour plot, and (F) 3D surface diagram; The impacts of various independent factors on IL-6 serum levels in rats following the administration of various MZ-PO-TX-NEs as shown in the (G) perturbation, (H) contour, and (I) 3D surface diagrams; The influences of various explored parameters on MIC values following the use of various MZ-PO-TX-NEs are shown in the (J) perturbation, (K) contour, and (L) 3D surface diagrams.
Figure 5
Figure 5
In vitro release profiles of MZ from optimal NE and MZ aqueous dispersion.
Figure 6
Figure 6
In vitro release of MZ from different lozenges and the drug aqueous suspension.
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References

    1. Passarelli P.C., Pagnoni S., Piccirillo G.B., Desantis V., Benegiamo M., Liguori A., Papa R., Papi P., Pompa G., D’Addona A. Reasons for Tooth Extractions and Related Risk Factors in Adult Patients: A Cohort Study. Int. J. Environ. Res. Public Health. 2020;17:2575. doi: 10.3390/ijerph17072575. - DOI - PMC - PubMed
    1. Beuling M.G., Agterbos P.C.G., van Riet P.C.T., Ho J.P.T.F., de Vries R., Kober J., de Lange J. Forces and movements during tooth extraction: A scoping review. Adv. Oral Maxillofacial Surg. 2023;9:100391. doi: 10.1016/j.adoms.2023.100391. - DOI
    1. Arteagoitia I., Ramos E., Santamaria G., Barbier L., Alvarez J., Santamaria J. Amoxicillin/clavulanic acid 2000/125 mg to prevent complications due to infection following completely bone-impacted lower third molar removal: A clinical trial. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2015;119:8–16. doi: 10.1016/j.oooo.2014.08.014. - DOI - PubMed
    1. Kassebaum N.J., Bernabé E., Dahiya M., Bhandari B., Murray C.J.L., Marcenes W. Global Burden of Severe Tooth Loss: A Systematic Review and Meta-analysis. J. Dent. Res. 2014;93((Suppl. S7)):20S–28S. doi: 10.1177/0022034514537828. - DOI - PMC - PubMed
    1. Chrysanthakopoulos N.A. Reasons for extraction of permanent teeth in Greece: A five-year follow-up study. Int. Dent. J. 2011;61:19–24. doi: 10.1111/j.1875-595X.2011.00004.x. - DOI - PMC - PubMed

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