• NEELAM SINGH Department of Pharmaceutics, ITS College of Pharmacy, NH-58, Ghaziabad - 201 206, Uttar Pradesh, India.
  • Giriraj T Kulkarni Amity Institute of Pharmacy, Amity University Uttar Pradesh, Sector 125, Noida 201303, India
  • Yatendra Kumar I.T.S College of Pharmacy, NH-58, Delhi Meerut road, Ghaziabad, 201206, India
  • GIRIRAJ T KULKARNI Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Sector 125, Noida - 201 303, Uttar Pradesh, India.


Objective: Pharmacokinetic evaluation of montelukast sodium chronomodulated capsules (sustained-release solid dispersion of drug enclosed in pH-sensitive film-coated hard gelatin shell) and marketed tablets has been carried out in this study.

Methods: A single oral dose of prepared capsules and marketed conventional tablets was administered in healthy male Dunkin-Hartley albino guinea pigs. Blood samples were collected at different time intervals and plasma concentration of drug was determined by reversed-phase high-performance liquid chromatography. Different pharmacokinetic parameters were assessed from plasma drug concentration-time profile by one-compartment model, first-order kinetics.

Results: Pharmacokinetic parameters such as time to reach maximum concentration, elimination rate constant, elimination half-life, and mean residence time data indicates that drug release from chronomodulated capsules is significantly prolonged with initial release lag time of 3.5–4 h in comparison with marketed conventional tablets. However, maximum drug plasma concentration, area under the concentration-time curve, and apparent volume of distribution values show non-significant difference between capsules and marketed tablets.

Conclusion: The findings specified that capsules were providing time controlled delivery of drug at a desired rate for prolonged time, which may be helpful for the prevention of episodic attack of asthma in early morning hours.

Keywords: Montelukast sodium, Pharmacokinetics, High-performance liquid chromatography, Guinea pig plasma, Sustained-release solid dispersion, pH-sensitive coating.

Author Biography

NEELAM SINGH, Department of Pharmaceutics, ITS College of Pharmacy, NH-58, Ghaziabad - 201 206, Uttar Pradesh, India.



1. Yu RH, Cao YX. A method to determine pharmacokinetic parameters based on andante constant-rate intravenous infusion. Sci Rep 2017;7:13279.
2. Urso R, Blardi P, Giorgi G. A short introduction to pharmacokinetics. Eur Rev Med Pharm Sci 2002;6:33-44.
3. Claesson HE, Dahlen SE. Asthma and leukotrienes: Antileukotrienes modifier agents. J Natl Med Assoc 1999;245:205-27.
4. Mastalerz L, Kumik J. Antileukotriene drugs in the treatment of asthma. Pol Arch Med Wewn 2010;120:103-8.
5. McIvor RA, Kaplan A, Koch C, Sampalis JS. Montelukast as an alternative to low-dose inhaled corticosteroids in the management of mild asthma (the SIMPLE trial): An open-label effectiveness trial. Can Respir J 2009;16 Suppl A:11A-21A.
6. Muralidharan S, Qi LG,Yi L, Kaur N, Parasuraman S, Kumar J, et al. Newly developed and validated method of montelukast sodium estimation in tablet dosage form by ultraviolet spectroscopy and reverse phase-high performance liquid chromatography. PTB Rep 2016;2:27-30.
7. Soni R, Sagar GV, Sharma P. Formulation, development and in-vitro evaluation of mucoadhesive bilayered buccal patches of montelukast sodium. Int J Pharm Pharm Sci 2012;4:484-97.
8. Zhao JJ, Rogers JD, Holland SD, Larson P, Amin RD, Haesen R, et al. Pharmacokinetics and bioavailability of montelukast sodium (MK- 0476) in healthy young and elderly volunteers. Biopharm Drug Dispos 1997;18:769-77.
9. Narin I, Sarioglan S, Anilanmert B, Sari H. Pka determinations for montelukast sodium and levodropropizine. J Solut Chem 2010;39:1582-8.
10. Panchal R, Patel H, Patel V, Joshi P, Parikh A. Formulation and evaluation of montelukast sodium - Chitosan based spray dried microspheres for pulmonary drug delivery. J Pharm Bioallied Sci 2012;4:S110-1.
11. Mohammed SS, Alhas JJK, Siraj S. Study on the impact of patient counseling on the quality of life and pulmonary function of asthmatic patient. Int J Pharm Pharm Sci 2012;4:300-4.
12. Shafaati A, Zarghi A, Foroutan SM, Khoddam A, Madadian B. Rapid and sensitive determination of Montelukast in human plasma by high performance liquid chromatographic method using monolithic column application to pharmacokinetic studies. J Bioequiv 2010;2:135-8.
13. Ranjan OP, Nayak UY, Reddy MS, Dengale SJ, Musmade PB, Udupa N, et al. Development and validation of RP-HPLC method with ultraviolet detection for estimation of montelukast in rabbit plasma: Application to preclinical pharmacokinetics. J Young Pharm 2013;5:133-8.
14. Al-Tamimi JJ. Development and validation of HPLC/UV method, for determination of meloxicam in human plasma and application in pharmacokinetic studies. Int J Pharm Pharm Sci 2015;7:370-7.
15. Bae JW, Kim MJ, Jang CG, Lee SY. Determination of meloxicam in human plasma using a HPLC method with UV detection and its application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2007;859:69-73.
16. Vaghela A, Patel A, Patel A, Vyas A, Patel. Sample preparation in bioanalysis: A review. Int J Sci Technol Res 2016;5:6-10.
17. National Academic Press. Guide for the Care and Use on Laboratory Animals. 8th ed. Washington, DC: National Academic Press; 2011.
18. Qureshi MD, Ali J, Baboota S, Ahuja A, Mallikarjun C. Pharmacokinetic study of a capsule based chronomodulated drug delivery system of salbutamol sulphate in rabbits.Trop J Pharm Res 2014;13:17-22.
19. de Almeida Gonçalves G, de Sá-Nakanishi AB, Wendt MM, Comar JF, Bersani Amado CA, Bracht A, et al. Green tea extract improves the oxidative state of the liver and brain in rats with adjuvant-induced arthritis. Food Funct 2015;6:2701-11.
20. Patil-Gadhe A, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: Part I oral bioavailability improvement. Eur J Pharm Biopharm 2014;88:160-8.
21. Birck MM, Tveden-Nyborg P, Lindblad MM, Lykkesfeldt J. Non-terminal blood sampling techniques in guinea pigs. J Vis Exp 2014;92:e51982.
22. Sangeetha S, Malay K Samanta, Kavitha R, Remya PN, Saraswathi TS. Formulation and pharmacokinetic determination of gallic acid in Emblica officinalis. Int J Appl Pharm 2017;9:9-13.
23. Parra MA, Pabon JP, Meesters RJ. Bioanalytical evaluation of dried plasma spot microsampling methodologies in pharmacokinetic studies applying acetaminophen as model drug. J Appl Bioanal 2016;2:25-37.
24. Soy D, Beal SL, Sheiner LB. Population one-compartment pharmacokinetic analysis with missing dosage data. Clin Pharmacol Ther 2004;76:441-51.
25. Zhang Y, Qian D, Pan Y, Zhu Z, Huang J, Xi J, et al. Comparisons of the pharmacokinetic profile of four bioactive components after oral administration of gan-sui-ban-xia decoction plus-minus gansui and gancao drug combination in normal rats. Molecules 2015;20:9295-308.
26. Ranjan OP, Nayak UY, Reddy MS, Dengale SJ, Musmade PB, Udupa N, et al. Osmotically controlled pulsatile release capsule of montelukast sodium for chronotherapy: Statistical optimization, in vitro and in vivo evaluation. Drug Deliv 2014;21:509-18.
27. Priyanka K, Sathali AA. Preparation and evaluation of montelukast sodium loaded solid lipid nanoparticles. J Young Pharm 2012;4:129-37.
28. Fatima T, Rasheed A, Mahboob A, Ansari A, Fatimah A, Rafeeq H. Formulation and evaluation of time dependent release of montelukast tablets by using mini tablet technology. Indo Am J Pharm Res 2016;6:4002-12.
29. Gandhi AP, Kyadarkunte A, Patole M, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro – in vivo aerosol performance. Eur J Pharm Biopharm 2014;88:169-77.
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How to Cite
SINGH, N., G. Kulkarni, Y. Kumar, and G. T KULKARNI. “PHARMACOKINETIC COMPARISON OF MONTELUKAST SODIUM FORMULATIONS AFTER A SINGLE ORAL DOSE IN HEALTHY GUINEA PIGS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 2, Jan. 2019, pp. 165-9,
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