Comparative study of the biopharmaceutical quality of Clonazepam 0.5 mg commercialized in the Peruvian market.
Keywords:
Clonazepam, interchangeability, quality controlAbstract
Introduction: Clonazepam belongs to a group of medications called benzodiazepines. It is known that these drugs act in the brain through GABA. It is an anticonvulsant used for various types of attacks, including myotonic or atonic attacks, photosensitive epilepsy, and absence attacks, although tolerance may develop. It is rarely effective in generalized or partial tonic-clonic attacks.
Method: the present study was carried out to analyze the comparative parameters of in vitro quality control by evaluating the variation in weight, friability, hardness, disintegration time and dissolution profile between the innovative drug (Rivotril®) and multi-source drugs that are marketed in the Peruvian market. To carry out the comparative study, Clonazepam 0.5 mg multi-source tablets were selected from different laboratories comparing them with the innovative medicine and the physicochemical and biopharmaceutical characteristics were evaluated. Pharmacopoeial trials were evaluated as established in USP 42.
Results: the results made it possible to establish that all the brands analyzed met the acceptance criteria established in the pharmacopoeia for each active ingredient and that their biopharmaceutical behavior was very similar for both types of molecule.
Conclusions: it was established that all Clonazepam 0.5 mg multi-source tablets included in this research are bioequivalent with the chosen innovative brand and, therefore, allow the determination of biopharmaceutical equivalence as a support element in decision-making to be proposed to the scientific community purchase in the pharmaceutical service
Introduction: Clonazepam belongs to a group of medications called benzodiazepines. It is known that these drugs act in the brain through GABA. It is an anticonvulsant used for various types of attacks, including myotonic or atonic attacks, photosensitive epilepsy, and absence attacks, although tolerance may develop. It is rarely effective in generalized or partial tonic-clonic attacks.
Method: the present study was carried out to analyze the comparative parameters of in vitro quality control by evaluating the variation in weight, friability, hardness, disintegration time and dissolution profile between the innovative drug (Rivotril®) and multi-source drugs that are marketed in the Peruvian market. To carry out the comparative study, Clonazepam 0.5 mg multi-source tablets were selected from different laboratories comparing them with the innovative medicine and the physicochemical and biopharmaceutical characteristics were evaluated. Pharmacopoeial trials were evaluated as established in USP 42.
Results: the results made it possible to establish that all the brands analyzed met the acceptance criteria established in the pharmacopoeia for each active ingredient and that their biopharmaceutical behavior was very similar for both types of molecule.
Conclusions: it was established that all Clonazepam 0.5 mg multi-source tablets included in this research are bioequivalent with the chosen innovative brand and, therefore, allow the determination of biopharmaceutical equivalence as a support element in decision-making to be proposed to the scientific community purchase in the pharmaceutical service
Downloads
References
Jiménez L, Rodriguez Y. Determinación de una técnica selectiva por cromatografía en capa fina para identificación de benzodiazepinas. Universidad Norbert Wiener; 2017. 10 p.
FDA– Food and Drug Administration U.S. Food & Drug Administration: Guía para la Industria: Pruebas de disolución de formas de dosificación oral sólidas de liberación inmediata. Centro de Evaluación e Investigación de Drogas. Guidances (Drugs).1997. [citado 10 dic 2019] Disponible en: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guia-para-la-industria-pruebas-de-disolucion-de-formas-de-dosificacion-oral-solidas-de-liberacion.
Comparability Protocols for Human Drugs and Biologics [Internet]. FDA – Food and Drug Administration U.S.: Guidance for Industry Guidance for Industry Contains Nonbinding Recommendations. 2016. [citado 12 dic 2019]. Disponible en: http://www.fda.gov/CombinationProducts/default.htm
Amidon G, Lennernäs H, et al. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo. AAPSj. 1995;12(1):413-420.
Fatima S, Jamil S, et al. In-vitro dissolution testing for therapeutic equivalence of metronidazole immediate release tablets available in Karachi, Pakistan. Int J Pharm Sci Res. 2017; 8(7): 3133-37.
Iriarte, R. Desarrollo de Medios de Disolución Biorrelevantes para Fármacos con Problemas de Bioequivalencia. Universidad Miguel Hernández, España, 2015. 1-37.
Segura Campos L. “Medicamentos Genéricos: Su Importancia Económica En Los Sistemas Públicos de Salud y La Necesidad de Estudios in Vitro Para Establecer Su Bioequivalencia”. Pensamiento Actual. 2017 (28):108.
Amidon L, Hans L, Vinod P, et al. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability. AAPS J. 1995; 12(3): 413–20.
Granero L and Polache A. Absorption of Drugs after Oral Administration. Int Pharm Sci Encyclopedia.2010.
Ono A and Kiyohiko S. Application of the BCS Biowaiver Approach to Assessing Bioequivalence of Orally Disintegrating Tablets with Immediate Release Formulations. Eur J Pharm Sci 2014;64 (11): 37–43.
Shah P, Flavian Ş, et al. Commonality between BCS and TCS. Int J Pharm. 2016: 509 (2): 35-40.
Baishya H, Gogoi B, Bordoloi D, Gogoi P. In-vitro evaluation of two marketed brands of dexamethasone tablets IP as per Indian pharmacopoeia Disponible en: Int J Res Pharmacy and Pharm Sci. 2018;3(1): 197-201
Domínguez V, Collares M, et al. Uso racional de benzodiacepinas: hacia una mejor prescripción. Rev Urug Med Int. 2016; 1(3): 14-24.
Farmacopea de los Estados Unidos de América, Formulario Nacional, USP, USP 42-NF 37, The Pharmacopeial Convention, United Book Press, Baltimore, 2019.
Kalakuntla UR, Veerlapati M, Chepuri R. Effect of various super disintegrants on hardness, disintegration and dissolution of medicine from dosage form. J Adv Sci Res. 2010; 1(1):15.
World Health Organization. Proposal to Waive the In Vivo Bioequivalence Requirements for the Model List of Essential Medicines Immediate Release, Solid Oral Dosage Forms. In WHO Expert Committee On Specifications for Pharmaceutical Preparations. Fortieth Report. Technical Report Series Nº 937. Annex 8. Geneva: World Health Organization; 2006.p.391- 437.
Karmakar P, Golam K. In-Vitro Comparative Evaluation of Quality Control Parameters between Paracetamol and Paracetamol/Caffeine Tablets Available in Bangladesh. Int C Pharm J Online (JOL). 2012; 103–9.
Musa H, Sule Y, Gwarzo M. Assessment of physicochemical properties of metronidazole tablets marketed in Zaria, Nigeria. Int J Pharm Pharm Sci. 2011; 3:27-29.
Murtha J, Julian T, Radebaugh G. Simultaneous determination of pseudoephedrine hydrochloride, chlorpheniramine maleate, and dextromethorphan hydrobromide by second‐derivative photodiode array spectroscopy. J Pharm Sci. 1988; 77(8):715-718.
Kostag K, Teixeira M, Costa M, De Almeida T, El Seoud O. Assessing cellulose dissolution efficiency in solvent systems based on a robust experimental quantification protocol and enthalpy data. Holzforschung. 2019; 73(12):1103-1112.
Manali D, PrajapataShital B, ButaniaMukesh C, Gohel B. Liquisolid: A promising technique to improve dissolution efficiency and bioavailability of poorly water soluble nimodipine. J Drug Deliv Sci Technol. 2019; 53:1773-2247.
Downloads
Published
How to Cite
Issue
Section
License
The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:
- The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.
b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.
c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).
