Development of the composition of meloxicam gel based on the results of biopharmaceutical studies

E. P. Bezuglaya, A. N. Lyapunov, V. V. Libina, I. N. Orlova, I. V. Kudris

Abstract


The meloxicam concentration and the composition of permeation enhancers in a gel for cutaneous application have been chosen on the basis of the results of pharmacological screening on the model of acute aseptic carrageenan inflammation of the rat’s paw. The efficiency of the analgesic effect of gels increases with increasing the meloxicam content, and the efficiency of the anti-inflammatory activity passes through a maximum at the meloxicam concentration of 1.0-1.5%. The efficiency of the anti-inflammatory and analgesic effects is the highest when gels contain 15% of N-methylpyrrolidone and 25% of ethanol (96%). Due to the content of hydrophilic non-aqueous solvents the gel base possesses the osmotic activity, whereby providing the moderate water absorption by the drug and prolonged release of meloxicam from the gel in experiments in vitro. Such properties of the gel, on the one hand, are an important prerequisite for transdermal absorption of meloxicam, on the other hand, the dehydrating action onto the skin is not expected. Pharmacokinetic studies of 1% gel of meloxicam were conducted compared to the intramuscular (i/m) administration of Movalis injection of 15 mg/1.5 ml. The analytical procedure (liquid chromatography with the solid phase extraction of the active substance from the plasma) has been developed and validated for analytical support of the pharmacokinetic studies. It has been found in the experiment on rabbits that in case of cutaneous application of the gel meloxicam is absorbed slowly and continuously into the systemic circulation at a relatively high extent of transdermal absorption and slow elimination. Therefore, it can be expected that the gel developed provides the effective prolonged therapeutic action.


Keywords


meloxicam; gel; analgesic effect; anti-inflammatory effect; release; pharmacokinetics

References


The Rules Governing Medicinal Products in the European Union. – The Notice to Applicants. – Volume 2C. Regulatory Guidelines. – Guideline on the Categorisation of Extension Applications (EA) versus Variations Applications (V). –European Comission. – Brüssels, F2/AW D(2002), Final – Revision 3.

EMEA/СHМР/167068/2004 – ICH. – Part I. – ICH Topic Q 8 (R2). – Step 5: Note for Guidance on Pharmaceutical Development, 2009.

Martindale: The Complete Drug Reference. 36th Edition / Ed. Sweetman S.С. – London: Pharmaceutical Press, 2009. – 3694 p.

Державний реєстр лікарських засобів України [Електронний ресурс]. Режим доступу: http://www.drlz.kiev.ua/

Государственный реестр лекарственных средств России [Электронный ресурс]. Ре-жим доступа: http://grls.rosminzdrav.ru/

Глава 9. Фармацевтическая разработка лекарственных препаратов / Ляпунов Н.А., Безуглая Е.П., Столпер Ю.М. и др. // Аналитическая химия в создании, стандартизации и контроле качества лекарственных средств (в 3 томах) / Под ред. В.П. Георгиевского. – Том 3. Метрологическое и нормативное обеспечение создания, производства и контроля качества лекарственных средств. – Харьков: Изд-во «НТМТ», 2011. – Т. 3. – С. 1419-1512.

Carbopol® Ultrez 21 Polymer // Technical Data Sheet (TDS-297). – Cleveland: Lubrizol, 2002. – 4 p.

European Pharmacopoeia. 8th Edition. – European Directorate for the Quality of Medi-cines (EDQM). – Council of Europe, 67075 Strasbourg Cedex, France 2013. – 3655 p.

Lugano A.S. Etude du transport de principles actifs incorpores dans des emulsions liq-uides de type huile dans eau: These doct. pharm. sci. – 1793. – Zurich, 1977. – 117 s.

Методические рекомендации по экспериментальному (доклиническому) изучению лекарственных препаратов для местного лечения гнойных ран / Даценко Б.М., Калиниченко Н.Ф., Лепахин В.К. и др. – М., 1989. – 45 с.

Шварц Г.Я., Сюбаев Р.Д. Методические рекомендации по доклиническому изучению нестероидных противовоспалительных лекарственных средств // Руководство по проведению доклинических исследований лекарственных средств. Ч. 1. / Ред. А.Н. Миронов. – М.: Гриф и К, 2012. – С. 746-758.

Лапач С.Н., Чубенко А.В., Бабич П.Н. Статистические методы в биологических исследованиях с использованием Excel. – К.: Морион, 2000. – 320 с.

Guidance for Industry: Bioanalytical Methods Validation / FDA, CDER, 2001/. [Elec-tronic resource]. Mode of access: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guid-ances/UCM368107.pdf

Валидация биоаналитического метода: методические рекомендации / Чумак В.Т., Баула О.П., Скакун Н.Н. и др. // Вісник фармакології та фармації. – 2009. – № 10. – С. 43-59.

EMEA/CHMP/EWP/192217/2009 Rev.1 Corr.* Guideline on bioanalytical method validation, 2011 [Electronic resource]. Mode of access: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/ 2011/ 08/WC500109686.pdf


GOST Style Citations






DOI: https://doi.org/10.24959/cphj.15.1355

Abbreviated key title: Klìn. farm.

ISSN 2518-1572 (Online), ISSN 1562-725X (Print)