Prediction of in vivo performance of ibuprofen immediate-release products using different dissolution models

Fatma Abdelfattah Nesrin Taha Aya Abdou Nadia Mursi Laila Emara   

Open Access   

Published:  Jun 16, 2022


This study explored the role of different compendial dissolution apparatuses in predicting the pharmacokinetic performance of ibuprofen (IBU) immediate-release (IR) commercial products. Dissolution studies of 200 mg IBU IR tablets of Brufen® (Abbott, Egypt), Nurofen® (Reckitt Benckiser Healthcare, Belgium), and Advil® (Pfizer, USA) were carried out employing the United States Pharmacopeia (USP) I, II, and IV models. Comparison of dissolution profiles was carried out using fit factors, mean dissolution time, and dissolution efficiency. Prediction of in vivo plasma concentration–time profile from in vitro data was carried out by back-calculation of the Wagner–Nelson approach. In vitro/in vivo correlation (IVIVC) was verified between the predicted and actual pharmacokinetic parameters with an estimation of prediction error (PE%). USP II and IV met the accepted dissolution criterion (80% of the label dissolved in 60 minutes) for all IBU IR products, while USP I failed. All commercial tablets showed dissimilar dissolution profiles in all studied models, except Advil versus Nurofen in USP IV. The best IVIVC (R2 values ≥ 0.99 and intercept values close to zero) were observed for Advil in USP II and IV as well as Brufen and Nurofen in USP IV. Accepted PE% values in terms of Cmax and AUCs were achieved for all products in USP IV. The USP IV dissolution model was utilized as a predictive tool for in vivo performances of IBU IR products especially during early product development and, hence, might be adopted as a surrogate for conducting clinical bioequivalence studies.

Keyword:     IVIVC ibuprofen Wagner– Nelson deconvolution USP compendial models flowthrough cell.


Abdelfattah F, Taha N, Abdou A, Mursi N, Emara L. Prediction of in vivo performance of ibuprofen immediaterelease products using different dissolution models. J Appl Pharm Sci, 2022. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


Bose A, Wui WT. Convolution and validation of in vitro-in-vivo correlation of water-insoluble sustained-release drug (domperidone) by first-order pharmacokinetic one-compartmental model fitting equation. Eur J Drug Metab Pharmacokinet, 2013; 38(3):191-200.

Bredael GM, Liang S, Hahn D. A strategy for quality control dissolution method development for immediate-release solid oral dosage forms. Dissolution Technol, 2015; 22:10-6.

Chakraborty S, Pandya K, Aggarwal D. Establishing prospective IVIVC for generic pharmaceuticals: methodologies assessment. Drug Deliv, 2014; 5(1).

Chevalier E, Viana M, Artaud A, Chomette L, Haddouchi S, Devidts G, Chulia D. Comparison of three dissolution apparatuses for testing calcium phosphate pellets used as ibuprofen delivery systems. AAPS PharmSciTech, 2009; 10(2):597-605.

Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci, 2001; 13(2):123-33.

Emam MF, Taha NF, Mursi NM, Emara LH. Preparation, characterization and in-vitro/in-vivo evaluation of meloxicam extruded pellets with enhanced bioavailability and stability. Drug Dev Ind Pharm. 2021; 47(1):163-75.

Emara L, El-Menshawi B, Estefan M. In vitro-in-vivocorrelation and comparative bioavailablity of vincamine in prolonged-release preparations. Drug Dev Ind Pharm, 2000; 26(3):243-51.

Emara LH, Taha NF, Mursi NM. Investigation of the effect of different flow-through cell designs on the release of diclofenac sodium SR tablets. Dissolution Technol, 2009; 16(2):23-31.

Emara LH, Abdelfattah FM, Taha NF, El-Ashmawy AA, Mursi NM. In-vitroevaluation of ibuprofen hot-melt extruded pellets employing different designs of the flow through cell. Int J Pharm Pharm Sci, 2014a; 6:192-7.

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 Pharmaceutic Sci, 2014b; 6(11):254-60.

Forrest WP, Reuter KG, Shah V, Kazakevich I, Heslinga M, Dudhat S, Patel S, Neri C, Mao Y. USP apparatus 4: a valuable in-vitrotool to enable formulation development of long-acting parenteral (LAP) nanosuspension formulations of poorly water-soluble compounds. AAPS PharmSciTech, 2018; 19(1):413-24.

Hashem HM, Abdou AR, Mursi NM, Emara LH. Comparative in-vitrodissolution study on metformin market products using different dissolution apparatuses. Int J Pharm Pharm Sci, 2019; 11(9):65-72.

Higgins JD, Gilmor TP, Martellucci SA, Bruce RD, Brittain HG. Ibuprofen. In: Harry GB (eds.). Analytical profiles of drug substances and excipients, vol. 27. Academic Press, Cambridge, MA, pp 265-300, 2001.

Khan F, Li M, Schlindwein W. Comparison of in-vitrodissolution tests for commercially available aspirin tablets. Dissolution Technol, 2013; 20(1):48-58.

Lu Z, Fassihi R. Mechanistic approach to understanding the influence of USP apparatus I and II on dissolution kinetics of tablets with different operating release mechanisms. AAPS PharmSciTech, 2017; 18(2):462-72.

Medina JR, Cortes M, Romo E. Comparison of the USP apparatus 2 and 4 for testing the in-vitrorelease performance of ibuprofen generic suspensions. Int J Appl Pharm, 2017; 9(4):90-5.

Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol, 1996; 20(6):64-74.

Ostrowski M, Baczek T, Wilkowska E. The influence of averaging procedure on the accuracy of IVIVC predictions: immediate release dosage form case study. J Pharm Sci, 2010; 99(12):5040-5.

Rainsford K. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology, 2009; 17(6):275-342.

Reddy BBK, Karunakar A. Biopharmaceutics classification system: a regulatory approach. Dissolution Technol, 2011; 18(1):31-7.

Shah VP, Lesko L, Fan J, Fleischer N, Handerson J, Malinowski H, Makary M, Ouderkirk L, Roy S, Sathe P. FDA guidance for industry: dissolution testing of immediate release solid oral dosage forms. Dissolution Technol, 1997; 4(4):15-22.

Shin D, Lee SJ, Ha Y-M, Choi Y-S, Kim J-W, Park S-R, Park MK. Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen. Drug Des Devel Ther, 2017; 11:135-41.

Taha NF, Emam MF, Emara LH. A novel combination of Soluplus®/Poloxamer for Meloxicam solid dispersions via hot melt extrusion for rapid onset of action. Part 2: comparative bioavailability and IVIVC. Drug Dev Ind Pharm., 2020; 46(8):1362-72.

Tamilvanan S, Sa B. In-vitroand in-vivoevaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of ibuprofen. AAPS PharmSciTech, 2006; 7(3):E126-34.

Todaro V, Persoons T, Grove G, Healy AM, D'Arcy DM. Characterization and simulation of hydrodynamics in the paddle, basket and flow-through dissolution testing apparatuses-a review. Dissolution Technol, 2017; 24:24-36.

USP-32. United State Pharmacopeia and National Formulary USP 32-NF 27; The United States Pharmacopeial Convention. Inc, Rockville MD, 2009

Wei H, Löbenberg R. Biorelevant dissolution media as a predictive tool for glyburide a class II drug. Eur J Pharm Sci, 2006; 29(1):45-52.

Yoshida H, Kuwana A, Shibata H, Izutsu K-i, Goda Y. Effects of pump pulsation on hydrodynamic properties and dissolution profiles in flowthrough dissolution systems (USP 4). Pharm Res, 2016; 33(6):1327-36.

Zhang L, Ha K, Kleintop B, Phillips S, Scheer B. Differences in in-vitrodissolution rates using single-point and multi-point sampling. Dissolution Technol, 2007; 14(4):27-31.

Article Metrics

1 Absract views 0 PDF Downloads 1 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required