IN VITRO IN VIVO CORRELATION OF DEXTROMETHORPHAN HYDROBROMIDE MODIFIED RELEASE TABLETS: AN INTERNAL VALIDATION EVALUATION
Abstract
ABSTRACT
Objectives: The purpose of this study was to develop and validate in vitro and in vivo correlation (IVIVC) for newly developed dextromethorphan
hydrobromide sustained-release (SR).
Methods: During the development of a once-daily SR tablet of dextromethorphan hydrobromide, an extrapolative in vitro drug release method was
designed and statistically evaluated using three formulations with varying release rates. The similarity factor (f2) was used to analyze the dissolution
data. Three-way crossover study design was conducted in six healthy human subjects under fasting condition.
Result: The formulations were evaluated by using area under the plasma concentration-time curve, (AUC0-∞), time to reach peak plasma concentration,
Tmax, and peak plasma concentration Cmax, while correlation was determined between in-vitro release and in-vivo absorption. A linear correlation
was observed between the absorption and dissolution profiles of the drug. The prediction error (%) was determined to check how well a given model
can accurately predict a pharmacokinetic parameter of the drug. The predicted Cmax and AUC found to be −6.98 and −8.55 and for AUC was 7.76 and
8.82% respectively.
Conclusion: In conclusion, a Level A IVIVC explaining the complete time-course of plasma concentrations was developed and validated, internally for
developed dextromethorphan hydrobromide SR formulations.
Keywords: Dextromethorphan hydrobromide, Dissolution, Bioavailability, Sustained-release, In vitro and in vivo correlation.
Downloads
References
REFERENCES
Food and Drug Administration. Guidance for industry: Extended release oral dosage forms: Development, evaluation, and application of in vitro/in vivo correlations. Rockville: FDA; 1997.
Silvasti M, Karttunen P, Tukiainen H, Kokkonen P, Hänninen U, Nykänen S. Pharmacokinetics of dextromethorphan and dextrorphan: a single dose comparison of three preparations in human volunteers. Int J Clin Pharmacol Ther Toxicol 1987;25(9):493-7.
Meyyanathan SN, Rajan S, Muralidaharan S, Siddaiah MK, Krishnaraj K, Suresh B. Formulation and evaluation of dextromethorphan hydrobromide sustained release tablets. Drug Deliv 2008;15(7):429-35.
Takka S, Sakr A, Goldberg A. Development and validation of an in vitro-in vivo correlation for buspirone hydrochloride extended release tablets. J Control Release 2003;88(1):147-57.
Eddington ND, Marroum P, Uppoor R, Hussain A, Augsburger L. Development and internal validation of an in vitro-in vivo correlation for a hydrophilic metoprolol tartrate extended release tablet formulation. Pharm Res 1998;15(3):466-73.
Mirza T, Bykadi SA, Ellison CD, Yang Y, Davit BM, Khan MA. Use of in vitro-in vivo correlation to predict the pharmacokinetics of several products containing a BCS class 1 drug in extended release matrices. Pharm Res 2013;30(1):179-90.
Galia E, Nicolaides E, Hörter D, Löbenberg R, Reppas C, Dressman JB. Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs. Pharm Res 1998;15(5):698-705.
Hayes S, Dunne A, Smart T, Davis J. Interpretation and optimization of the dissolution specifications for a modified release product with an in vivo-in vitro correlation (IVIVC). J Pharm Sci 2004;93(3):571-81.
Fujisaki Y, Tsukune T, Funyû M, Okumura M, Ukigaya T, Sugibayashi K. Development of sustained-release tablets containing sodium valproate: in vitro and in vivo correlation. Drug Dev Ind Pharm 2006;32(2):207-17.
Balan G, Timmins P, Greene DS, Marathe PH. In vitro-in vivo correlation (IVIVC) models for metformin after administration of modified-release (MR) oral dosage forms to healthy human volunteers. J Pharm Sci 2001;90(8):1176-85.
Sorasucharti W, Ayres JW. Preliminary bioequivalence testing of two nicardipine hcl sustained-release formulations with in vitro/in vivo correlations. European J Drug Metab Pharmacokinet 2001;26(1-2):I-7.
Meyer MC, Straughn AB, Mhatre RM, Shah VP, Williams RL, Lesko LJ. The relative bioavailability and in vivo-in vitro correlations for four marketed carbamazepine tablets. Pharm Res 1998;15(11):1787-91.
Szakács T, Veres Z, Vereczkey L. In vitro-in vivo correlation of the pharmacokinetics of vinpocetine. Pol J Pharmacol 2001;53(6):623-8.
Qiu Y, Garren J, Samara E, Cao G, Abraham C, Cheskin HS, et al. Once-a-day controlled-release dosage form of divalproex sodium II: development of a predictive in vitro drug release method. J Pharm Sci 2003;92(11):2317-25.
Sirisuth N. Systematic method for the development and validation of an IVIVC metoprolol and naproxen drug examples. Int J Gen Drug 2002;3:250-8.
Eddington ND. In vitro in vivo correlation with metoprolol extended release tablets using two different releasing formulations: An internal validation evaluation. Int J Gen Drug: 417-29.
Lootvoet G, Beyssac E, Shiu, G.K, Aiache JM, Ritschel WA. Study on the release of indomethacin from suppositories: In vitro-in vivo correlation. Int J Pharm 1992;85(1-3):113-20. Available from: http://www.dx.doi.org/10.1016/0378-5173(92)90140-W.
Dressman JB, Reppas C. In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. Eur J Pharm Sci 2000;11 Suppl 2:S73-80.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.