DISSOLUTION PERFORMANCE OF MELOXICAM FORMULATIONS UNDER HYDRODYNAMICS OF USP PADDLE APPARATUS AND FLOW-THROUGH CELL METHOD
Keywords:Meloxicam, Flow-through cell method, Generic formulations, USP paddle apparatus
Objective: To study the in vitro dissolution performance of four generic formulations of the poorly soluble drug meloxicam and the reference under hydrodynamic environments generated by flow-through cell method and USP paddle apparatus (pharmacopeial test).
Methods: Dissolution method was validated according to ICH guidelines. Dissolution profiles were carried out with an automated flow-through cell apparatus (laminar flow at 16 ml/min with 22.6 mm cells) and USP paddle apparatus at 75 rpm. Phosphate buffer pH 7.5 at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 362 nm was carried out during 30 min. Dissolution profiles were compared with model-dependent and-independent methods.
Results: Practically, all generic formulations showed significant differences with the percentage of drug dissolved at 30 min, mean dissolution time and dissolution efficiency, when USP paddle apparatus was used (*P<0.05), while only two generic formulations were different to reference using flow-through cell method. After adjustment to different mathematical equations, Weibull function was the best model to describe meloxicam dissolution performance and significant differences were found with all drug products when USP paddle apparatus was used, while only one formulation was different with flow-through cell method.
Conclusion: The study reveals the need to look for better dissolution schemes for meloxicam tablets since USP paddle apparatus may not reflect properly the in vitro dissolution performance of meloxicam generic formulations and reference.
Awasthi SS, Kumar TG, Manisha P, Preeti V, Kumar SS. Development of meloxicam formulations utilizing ternary complexation for solubility enhancement. Pak J Pharm Sci 2011;24:533‒9.
Silva Oliveira EF, Pimentel Azevedo RC, Bonfilio R, Borges de Oliveira D, Pereira Ribero G, Benjamim de Araujo M. Dissolution test optimization for meloxicam in the tablet pharmaceutical form. Braz J Pharm Sci 2009;45:67‒73.
Induri M, Mantripragada BR, Yejella RP, Kunda PR, Nannapaneni DT, Boddu R. Dissolution studies and quantification of meloxicam in tablet dosage form by spectrophotometry. Pak J Pharm Sci 2010;25:283‒7.
Food and Drug Administration. Guidance for Industry: Dissolution testing of immediate release solid dosage forms; 1997. Available from: https://www.fda.gov/downloads/ drugs/guidances/ucm070237.pdf. [Last accessed on 26 Mar 2019].
Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123‒33.
Yuksel N, Kanik AE, Baykara T. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and independent-methods. Int J Pharm 2000;209:57‒67.
United States Pharmacopeia and National Formulary USP 41-NF 36; The United States Pharmacopeial Convention, Inc: Rockville MD; 2018.
Qui S, Wang K, Li M. In vitro dissolution studies of immediate-release and extended-release formulations using flow-through cell apparatus 4. Dissol Technol 2014;21:6‒15.
Singh I, Aboul Enein HY. Advantages of USP Apparatus IV (flow-through cell apparatus) in dissolution studies. J Iran Chem Soc 2006;3:220‒2.
Sunesen VH, Pedersen BL, Kristensen HG, Müllertz A. In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media. Eur J Pharm Sci 2005;24:305‒13.
Szymanska E, Winnicka K. Comparison of flow-through cell and paddle methods for testing vaginal tablets containing a poorly water-soluble drug. Trop J Pharm Res 2013;12:39‒44.
Jantratid E, De Maio V, Ronda E, Mattavelli V, Vertzoni M, Dressman JB. Application of biorelevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form. Eur J Pharm Sci 2009;37:434‒41.
Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, et al. In vitro-in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol. J Controlled Release 2008;130:29‒37.
Fotaki N, Reppas C. The flow through cell methodology in the evaluation of intralumenal drug release characteristics. Dissol Technol 2005;12:17‒21.
Emara LH, Emam MF, Taha NF, El-Ashmawy AA, Mursi NM. In vitro dissolution study of meloxicam immediate release products using flow through cell (USP Apparatus 4) under different operational conditions. Int J Pharm Pharm Sci 2014;6:254‒60.
Ruiz ME, Gregorini A, Talevi A, Volonte MG. Dissolution studies of generic medications: new evidence of deviations from the transitivity principle. Dissol Technol 2012;19:13‒24.
Al Ameri MN, Nayuni N, Anil Kumar KG, Perrett D, Tucker A, Johnston A. The differences between the branded and generic medicines using solid dosage forms: in vitro dissolution testing. Results Pharm Sci 2012;2:1‒8.
COFEPRIS. Listado actualizado de medicamentos de referencia 2017/08, mexico. Available from: https://www.gob.mx/cms/ uploads/attachment/file/197452/lMR_2017-08_V006.pdf. [Last accessed on 26 Mar 2019].
ICH Harmonised Tripartite Guidelines. Q2B Validation of Analytical Procedures: Metodology. International Conference on Harmonization; 1996. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm073384.pdf [Last accessed on 26 Mar 2019]
Podczeck F. Comparison of in vitro dissolution profiles by calculating mean dissolution time (MDT) or mean residence time (MRT). Int J Pharm 1993;97:93‒100.
Anderson NH, Bauer M, Boussac N, Khan Malek R, Munden P, Sardaro M. An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles. J Pharm Biomed Anal 1998;17:811‒22.
Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DD solver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010;12:263‒71.
Medina JR, Ortiz HD, Hurtado M, Dominguez Ramirez AM. Influence of dose and the USP basket and flow-through cell dissolution apparatuses in the release kinetics of metronidazole immediate-release products. Int J Res Pharm Sci 2014;5:137‒46.
Medina JR, Salazar DK, Hurtado M, Cortes AR, Dominguez Ramirez AM. Comparative in vitro dissolution study of carbamazepine immediate-release products using the USP paddles method and the flow-through cell system. Saudi Pharm J 2014;22:141‒7.
Langenbucher F, Benz D, Kurth W, Moller H, Otz M. Standardized flow-cell method as an alternative to existing pharmacopoeial dissolution testing. Pharm Ind 1989;51:1276‒81.
Steffansen B, Brodin B, Und Nielsen C. editors. Molecular Biopharmaceutics. ULLA Pharmacy Series. Pharmaceutical Press; 2010.
Dermirtürk E, Oner L. In vitro-in vivo correlations. FABAD J Pharm Sci 2003;28:215‒24.
Medina JR, Uribe A, Hurtado M, Dominguez Ramirez AM. In vitro equivalence study of generic naproxen sodium tablets using the USP paddle apparatus and the flow-through cell method. Int J Pharm Pharm Sci 2015;7:348‒54.
Medina JR, Cortes M, Romo E. Comparison of the USP Apparatus 2 and 4 for testing the in vitro release performance of ibuprofen generic suspensions. Int J Appl Pharm 2017;9:90‒5.
Adams E, Coomans D, Smeyers Verbeke J, Massart DL. Non-linear mixed effects models for the evaluation of dissolution profiles. Int J Pharm 2002;240:37‒53.
Bhattachar SN, Wesley JA, Fioritto A, Martin PJ, Babu SR. Dissolution testing of a poorly soluble compound using the flow-through cell dissolution apparatus. Int J Pharm 2002;236:135‒43.
Chevalier E, Viana M, Artud A, Chomette L, Haddouchi S, Devidts G, et al. Comparison of three dissolution apparatuses for testing calcium phosphate pellets used as ibuprofen delivery systems. AAPS PharmSciTech 2009;10:597‒605.
Bertocchi P, Antoniella E, Valvo L, Alimonti S, Memoli A. Diclofenac sodium multisource prolonged release tablets-a comparative study on the dissolution profiles. J Pharm Biomed Anal 2005;37:679‒85.