Development of Composition and Technologies of Dental Gel of Meloxicam

Maria N. Anurova; Elena O. Bakhrushina; Natalya B. Demina; Alena Sergeevna Kashperko; Ekaterina D. Shevchenko; Elizaveta V. Leshcheva; Ivan I. Krasnyuk; Alaxander I. Bardakov

doi:10.3889/oamjms.2020.4541

Authors

Maria N. Anurova Sechenov First Moscow State University, Moscow, Russia
Elena O. Bakhrushina Sechenov First Moscow State University, Moscow, Russia https://orcid.org/0000-0001-8695-0346
Natalya B. Demina Sechenov First Moscow State University, Moscow, Russia
Alena Sergeevna Kashperko Sechenov First Moscow State University, Moscow, Russia https://orcid.org/0000-0002-9917-6772
Ekaterina D. Shevchenko Eberhard Karls Universität Tübingen, Tübingen, Germany
Elizaveta V. Leshcheva Sechenov First Moscow State University, Moscow, Russia
Ivan I. Krasnyuk Sechenov First Moscow State University, Moscow, Russia
Alaxander I. Bardakov Sechenov First Moscow State University, Moscow, Russia

DOI:

https://doi.org/10.3889/oamjms.2020.4541

Keywords:

meloxicam, dental gel, bioadhesion, mucin, rheology, local irritant effect

Abstract

BACKGROUND: Dental gels have several advantages over other oral dosage forms. Being a viscoplastic dosage form, the gel, when applied to the damaged area of the gum or mucous membrane, creates a protective film, preventing mechanical irritation, and providing a localized effect of the drug components.

AIM: The aim of this work was to develop the composition and technology of the dental gel of meloxicam, the study of the main technological and consumer characteristics, as well as the local irritating effect of the dosage form.

METHODS: Dental gels were prepared using purified water, alcohol, glycerol, and buckthorn oil as solvents, gelling agents used were: Hydroxyethylcellulose Natrosol® 250 HHX Pharm, Carbopol® 974P NF Polymer, and solubilizer Poloxamer 407 (Lutrol® F 127). The bioadhesive component and Noveon® Polycarbophil component were used for dental gel preparation. Aspartame was used as sweetener. Menthol and ascorbic acid were used to correct the organoleptic properties of the pharmaceutical composition. The formulated dental gel of meloxicam at a concentration of 7.5% was evaluated for organoleptic properties, pH, rheological characteristics, bioadhesive properties, and stability under the accelerated aging period. The in vivo local irritant effect was evaluated using ten rabbits by cutaneous, subcutaneous, subconjunctival administration, as well as application to the upper palate.

RESULTS: Based on the results of studying technological and organoleptic properties, the optimal composition based on the Natrosol® 250 HHX hydroxyethylcellulose gelling agent, glycerol solvent, and purified water in the ratio 1/5 was selected, the composition contains Noveon® bioadhesive in an amount of 2%. The composition has good taste, pH close to pH of saliva has high bioadhesive properties, satisfactory rheological characteristics. The shelf life of the experimental series by accelerated aging was 2 years. The selected composition does not have a local irritant effect.

CONCLUSION: A new dosage form of meloxicam was developed – a gel for use in dental practice.

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References

Cherkasov SM. Analysis of the prevalence of diseases of the dentofacial system, forming the demand for dental services. Fundam Res. 2014;2:186-9.

Miller K, Treloar T, Guelmann M, Rody W Jr., Shaddox LM. Clinical characteristics of localized aggressive periodontitis in primary dentition. J Clin Pediatr Dent. 2018;42(2):95-102. https://doi.org/10.17796/1053-4628-42.2.3 PMid:29087795

Monk AB, Harrison JE, Worthington HV, Teague A. Pharmacological interventions for pain relief during orthodontic treatment. Cochrane Database Syst Rev. 2017;11(11):CD003976. https://doi.org/10.1002/14651858. cd003976.pub2 PMid:29182798

Rigato HM, Mendes GD, Borges NC, Moreno RA. Meloxicam determination in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) in Brazilian bioequivalence studies. Int J Clin Pharmacol Ther. 2006;44(10):489-98. https://doi.org/10.5414/ cpp44489 PMid:17063980

Noble S, Balfour JA. Meloxicam. Drugs. 1996;51(3):424-30. PMid:8882380

Hopkins AL, Keserü GM, Leeson PD, Rees DC, Reynolds CH. The role of ligand efficiency metrics in drug discovery. Nat Rev Drug Discov. 2014;13(2):105-21. https://doi.org/10.1038/ nrd4163 PMid:24481311

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3-26. https://doi.org/10.1016/ s0169-409x(96)00423-1 PMid:11259830

Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov. 2007;6(11):881-90. https://doi.org/10.1038/nrd2445 PMid:17971784

Anurova MN, Bakhrushina EO, Demina NB. Review of contemporary gel-forming agents in the technology of dosage forms. Pharm Chem J. 2015;49:627-34. https://doi.org/10.1007/ s11094-015-1342-5

Anurova MN, Bakhrushina EO, Demina NB. The problem of taste masking of drugs. Drug Dev Regist. 2015;4(13):64-73.

Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A. 1991;88(7):2692-6. https://doi.org/10.1073/ pnas.88.7.2692 PMid:1849272

Anurova MN, Bakhrushina EO, Barnolitskiy GG, Krechetov SP. Justification of the rheological optimum in the development of semisolid forms. Dent Gels. 2017;2(19):58-62.

Puratchikody A, Prasanth VV, Mathew ST, Kumar BA. Development and characterization of mucoadhesive patches of salbutamol sulfate for unidirectional buccal drug delivery. Acta Pharm. 2011;61(2):157-70. https://doi.org/10.2478/ v10007-011-0011-9 PMid:21684844

Mironov AN, editors. Guidelines for Preclinical Studies of Drugs (Immunobiological Drugs). Part Two. Moscow: Grief and K; 2013.

Lapicque F, Vergne P, Jouzeau JI, Loeuille D, Gillet P, Vignon E, et al. Articular diffusion of meloxicam after a single oral dose: Relationship to cyclo-oxygenase inhibition in synovial cells. Clin Pharmacokinet. 2000;39(5):369-82. https://doi. org/10.2165/00003088-200039050-00005 PMid:11108435

Tilley SL, Coffman TM, Koller BH. Mixed messages: Modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest. 2001;108(1):15-23. https://doi. org/10.1172/jci200113416 PMid:11435451