IAI SPECIAL EDITION: Development and validation of dissolution testing of Flunarizine dihydrochloride in tablet dosage form
Keywords:Dissolution method, Flunarizine dihydrochloride , High-performance liquid , chromatography , Hyper-discriminating, Immediate release tablet
Background: Flunarizine dihydrochloride is an antivertigo, antimigraine, and adjunctive therapy for epilepsy, available in Indonesia as tablets. However, the dissolution test for the tablet dosage forms is not yet available in the Pharmacopoeia.
Objectives: To develop and validate the dissolution method of flunarizine dihydrochloride in tablets.
Methods: The dissolution profiles of three products were determined using three media (HCl 0.1N, acetate buffer pH 4.5, and 0.2% Tween 80 solution); two apparatus (basket and paddle); at three agitation speeds (50, 75, and 100rpm). The amount of drug released per unit time was measured by a validated High Performance Liquid Chromatography system.
Results: The method using a paddle apparatus at 50rpm in 900mL of 0.1N HCl medium was better hyperdiscriminating with a Q30 value ≥ 75% (p < 0.05). The selected method met the acceptance criteria in terms of precision, accuracy, and specificity.
AA Pharma Inc. (2010). Product Monograph Flunarizine Hydrochloride Capsules. Vaughan Ontario
Badan Pengawas Obat dan Makanan. (2020). Pusat Informasi Obat Nasional (online), Available from: http://pionas.pom.go.id/monografi/flunarizin. Jakarta
Balakrishnan, A., Rege, B. D., Amidon, G.L., & Polli, J.E. (2004). Surfactant-mediated dissolution: Contributions of solubility enhancement and relatively low micelle diffusivity. Journal of Pharmaceutical Sciences, 93(8), 2064–2075. https://doi.org/10.1002/jps.20118
Benet, L.Z. (2013). The Role of BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) in Drug Development. Journal of Pharmaceutical Sciences, 102(1), 34–42. https://doi.org/10.1002/jps.23359
Chen, L.R., Wesley, J.A., Bhattachar, S., Ruiz, B., Bahash, K., & Babu, S.R. 2003. Dissolution Behaviour of a Poorly Water-Soluble Compound in the Presence of Tween 80. Pharmaceutical Research, 20(5)
Chinese Pharmacopoeia Commission. (2011). Pharmacopoeia of the People's Republic of China 2010. Set of 3, English Edition, China Medical Science and Technology Press, Beijing
Holmes, B., Brogden, R.N., Heel, R.C., Speight, T.M., & Avery, G.S. (1984). Flunarizine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 27, 6–44. ADIS Press Limited. https://doi.org/10.2165/00003495-198427010-00002
ICH Harmonised Guideline. (2018). Biopharmaceutics Classification System-Based Biowaivers. M9. ICH Consensus Guideline
Krämer, J., Grady, L.T., & Gajendran, J. (2005). Historical Development of Dissolution Testing. In Dressman, J., and Krämer, J. Editor. Pharmaceutical Dissolution Testing. Taylor & Francis Group, LLC. ISBN-13: 978-0-8247-5467-9. Page. 14
Nagarajan, R. (2001). Polymer–Surfactant Interactions. In Detergents for the New Millennium, Proceeding of New Horizons Conference, American Oil Chemists Society and Consumer Specialty Products Association, Fort Myers, FL, Oct 14–17
The United States Pharmacopoeia (2016) 39–National Formulary 34, <1092> The Dissolution Procedure: Development and Validation. The United States Pharmacopoeial Convention, Inc.: Rockville, MD
Yelli, F., Lucida H., & Rivai, H. (2020). Development and Validation of Analytical Methods and Uniformity Content of Flunarizine Hydrochloride in Tablet Preparations. World Journal of Pharmacy and Pharmaceutical Sciences. 9(7), 55-66