Development of Pharmaceutical Equivalent Montelukast Sodium Immediate-Release, Film-Coated Tablets

Poowadon Muenraya, Apichart Atipairin, Teerapol Srichana, Narumon Changsan, Neelam Balekar, Somchai Sawatdee


Montelukast tablets are sold under the brand name Singulair and are used to control and prevent asthma symptoms. In this study, 10 mg film-coated montelukast tablets were developed as a generic drug in order to evaluate the pharmaceutical equivalent of the innovator’s products. The primary formulation ingredients used in all developed formulations (F1-F5) were the same as those described in the Singulair tablet package insert, except for formulations F3, F4, and F5, to which solubilizing enhancers were added to increase montelukast solubility. The core tablets were produced using the wet granulation method before being coated with HPMC polymer. FT-IR and DSC were used to determine drug and excipient compatibility. The micromeritic properties of the granules were assessed. The physicochemical properties of generated montelukast tablets and Singulair tablets were also investigated. The dissolution profiles of the tested drug and the innovator were assessed in a variety of pH mediums (pH 1.2, 4.5, 6.8, and water). The similarity (f2) and difference (f1) factors were computed. The accelerated and long-term stability of the tested drug in hot and humid climate zones was evaluated. The analytical method validation used in this study was ICH-acceptable for 8 parameters including specificity, range, linearity, accuracy, precision, limit of detection, limit of quantitation, and robustness. F1-F5 granules had similar properties, such as a pale-yellow color and excellent flow properties. There were no chemical interactions between montelukast and the excipients according to FT-IR and DSC analyses. The physical properties of all developed montelukast film-coated tablets were similar (average weight 212-218 mg; thickness 3.02-3.07 mm; assay 101-102% LA; disintegration time 3-4 min), except that the disintegration time of F3 was 8.10 min and that of F5 was 5.90 min, which was caused by the addition of poloxamer 188 to the formulation. In all mediums, only the F1 formula produced acceptable comparison dissolution profiles to Singulair. After 6 months of storage under accelerated and long-term conditions, the results showed the F1 formulation remained physically and chemically stable.


Alshora, D. H., M. A. Ibrahim, G. Zayed, M. A. Al Rwashed, H. A. Abou-Taleb, and M. F. Ali (2022). The Role of Sodium Lauryl Sulfate on Formulation of Directly Compressed Tablets Containing Simvastatin and Aspirin: Effect on Drugs Dissolution and Gastric Mucosa. Saudi Pharmaceutical Journal, 30(5); 635–645

Barbosa, J. S., F. A. Almeida Paz, and S. S. Braga (2016). Montelukast Medicines of Today and Tomorrow: From Molecular Pharmaceutics to Technological Formulations. Drug Delivery, 23(9); 3257–3265

Chen, Y., T. Feng, Y. Li, B. Du, and W. Weng (2017). Formulation and Evaluation of a Montelukast Sodium Orally Disintegrating Tablet with a Similar Dissolution Profile As the Marketed Product. Pharmaceutical Development and Technology, 22(2); 168–172

Davit, B., D. Conner, and L. Shargel (2016). Drug Product Performance, in Vivo: Bioavailability and Bioequivalence. Applied Biopharmaceutics & Pharmacokinetics; 469–528

Donald, L., G. M. Lampman, and G. S. Kriz (2001). Introduction to Spectroscopy: A Guide for Students of Organic Chemistry. Harcourt College Publishers

Dürig, T. and K. Karan (2019). Binders in Wet Granulation. In Handbook of Pharmaceutical Wet Granulation. Elsevier, pages 317–349

Eldin, A. B., A. A. Shalaby, and M. El-Tohamy (2011). Development and Validation of a HPLC Method for the Determination of Montelukast and its Degradation Products in Pharmaceutical Formulation Using an Experimental Design. Acta Pharmaceutica Sciencia, 53(1); 45–56

Ethiraj, T., R. Revathi, P. Thenmozhi, V. Saravanan, and V. Ganesan (2011). High Performance Liquid Chromatographic Method Development for Simultaneous Analysis of Doxofylline and Montelukast Sodium in a Combined Form. Pharmaceutical Methods, 2(4); 223–228

Gallelli, L., C. Palleria, A. De Vuono, L. Mumoli, P. Vasapollo, B. Piro, and E. Russo (2013). Safety and Efficacy of Generic Drugs with Respect to Brand Formulation. Journal of Pharmacology and Pharmacotherapeutics, 4; S110–S114

Goh, H. P., P. W. S. Heng, and C. V. Liew (2018). Comparative Evaluation of Powder Flow Parameters with Reference to Particle Size and Shape. International Journal of Pharmaceutics, 547(1); 133–141

Gombas, A., P. Szabó-Révész, M. Kata, G. Regdon, and I. Erős (2002). Quantitative Determination of Crystallinity of α-Lactose Monohydrate by DSC. Journal of Thermal Analysis and Calorimetry, 68(2); 503–510

González-González, O., I. O. Ramirez, B. I. Ramirez, P. O’Connell, M. P. Ballesteros, J. J. Torrado, and D. R. Serrano (2022). Drug Stability: ICH Versus Accelerated Predictive Stability Studies. Pharmaceutics, 14(11); 2324

Hadi, M. A., N. P. L. Babu, and A. S. Rao (2012). Formulation and Evaluation of Sustained Release Matrix Tablets of Montelukast Sodium. International Journal of Pharmacy, 2(3); 574–582

Hasan, M. I., S. A. Shimu, A. Akther, I. Jahan, M. Hamiduzzaman, and A. N. Hasan (2021). Development of Generic Drug Products by Pharmaceutical Industries Considering Regulatory Aspects: A Review. Journal of Biosciences and Medicines, 9(10); 23–39

Hiremath, P., K. Nuguru, and V. Agrahari (2019). Material Attributes and Their Impact on Wet Granulation Process Performance. In Handbook of Pharmaceutical Wet Granulation. Elsevier, pages 263–315

Jain, R. A. and A. S. Mundada (2015). Formulation, Development and Optimization of Fast Dissolving Oral Film of Montelukast Sodium. International Journal of Drug Development and Research, 7(4); 40–46

Jannin, V., E. Pochard, and O. Chambin (2006). Influence of Poloxamers on the Dissolution Performance and Stability of Controlled-Release Formulations Containing Precirol® ATO 5. International Journal of Pharmaceutics, 309(1-2); 6–15

Kim, Y. H., D. W. Kim, M. S. Kwon, T. K. Kwon, J. H. Park, S. G. Jin, K. S. Kim, Y. I. Kim, J. Park, and J. O. Kim (2015). Novel Montelukast Sodium-Loaded Clear Oral Solution Prepared with Hydroxypropyl-β-Cyclodextrin As a Solubilizer and Stabilizer: Enhanced Stability and Bioequivalence to Commercial Granules in Rats. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 82; 479–487

Kopp, S. (2006). Stability Testing of Pharmaceutical Products in a Global Environment. RAJ Pharma, 5; 291–294

Lee, K., E. Kim, S. Seo, and H. Choi (2008). Effect of Poloxamer on the Dissolution of Felodipine and Preparation of Controlled Release Matrix Tablets Containing Felodipine. Archives of Pharmacal Research, 31(8); 1023–1028

Lee, Y. J. and C. Kim (2020). Montelukast Use Over the Past 20 Years: Monitoring of Its Effects and Safety Issues. Clinical and Experimental Pediatrics, 63(10); 376

Mahant, S., A. Gaidhane, N. Dokrimare, K. Wadher, R. Lohiya, and M. Umekar (2020). Formulation and Evaluation of Fast Dissolving Tablet of Montelukast Sodium: Effect of Superdisintegrants. Scholars Academic Journal of Pharmacy, 9(2); 86–89

Mahesh, E., G. K. Kumar, M. G. Ahmed, and P. Kumar (2012). Formulation and Evaluation of Montelukast Sodium Fast Dissolving Tablets. Asian Journal of Biomedical and Pharmaceutical Sciences, 2(14); 75–82

Malik, A., V. Kumar, Renu, Sunil, and T. Kumar (2011). World Health Organization’s Guidelines for Stability Testing of Pharmaceutical Products. Journal of Chemical and Pharmaceutical Research, 3(2); 892–898

Martir, J., T. Flanagan, J. Mann, and N. Fotaki (2020). In Vivo Predictive Dissolution Testing of Montelukast Sodium Formulations Administered with Drinks and Soft Foods to Infants. AAPS PharmSciTech, 21(7); 1–8

Muñoz, E., D. Ocampo, E. E. Espinal, and N. Yépes (2014). Bioequivalence Study of Two 10 Mg Montelukast Immediate-Release Tablets Formulations: A Randomized, Single-Dose, Open-Label, Two Periods, Crossover Study. Crossover Study. J Bioequiv Avail, 6(3); 086–90

Nayak, A. (2004). A Review of Montelukast in the Treatment of Asthma and Allergic Rhinitis. Expert Opinion on Pharmacotherapy, 5(3); 679–686

Okumu, A., M. DiMaso, and R. Löbenberg (2008). Dynamic Dissolution Testing to Establish In Vitro/In Vivo Correlations for Montelukast Sodium, a Poorly Soluble Drug. Pharmaceutical Research, 25(12); 2778–2785

Paul J. Sheskey, G. P. M. D. J. G., Bruno C. Hancock (2020). Handbook of Pharmaceutical Excipients. Pharmaceutical Press, London

Prieto-Escolar, M., J. J. Torrado, C. Álvarez, A. Ruiz-Picazo, M. Simón-Vázquez, C. Govantes, J. Frias, A. García-Arieta, I. Gonzalez-Alvarez, and M. Bermejo (2021). One and Two-Step In Vitro-In Vivo Correlations Based on USP IV Dynamic Dissolution Applied to Four Sodium Montelukast Products. Pharmaceutics, 13(5); 690

Rajesh, M., G. Hariharaputhraayyanar, and R. Venkateshbabu (2019). Formulation and Evaluation of Sugar Free Chewable Tablets of Montelukast Sodium. International Journal of Pharmaceutical Sciences Review and Research, 56(1); 6–11

Rao, N. R., M. A. Hadi, H. Panchal, and B. Reddy (2012). Formulation and Evaluation of Biphasic Drug Delivery System of Montelukast Sodium for Chronotherapy. International Journal of Pharmaceutical and Chemical Sciences, 1(3); 757–775

Rashmitha, N., T. Raj, C. Srinivas, N. Srinivas, U. Ray, H. K. Sharma, K. Mukkanti, et al. (2010). A Validated RP-HPLC Method for Thedetermination of Impurities in Montelukast Sodium. Journal of Chemistry, 7(2); 555–563

Ratanajamit, C., B. Khwannimit, and K. Chotephinyononte (2017). An Open-Label, Randomized, Cross-Over Bioequivalence Study of Montelukast 10 mg Tablets in Healthy Thai Volunteers. Songklanakarin Journal of Science & Technology, 93(3); 335–340

Reddy, S. G., B. S. Kumar, K. Prashanthi, and H. A. Murthy (2023). Fabricating Transdermal Film Formulations of Montelukast Sodium with Improved Chemical Stability and Extended Drug Release. Heliyon, 9(3)

Sahu, R. and D. Jain (2020). Compatibility Studies of Montelukast with Pharmaceutical Excipients used in Tablet Formulations using Thermal and Chromatographic Techniques. Journal of Bioanalysis & Biomedicine, 12; 1–10

Šantl, M., I. Ilić, F. Vrečer, and S. Baumgartner (2012). A Compressibility and Compactibility Study of Real Tableting Mixtures: The Effect of Granule Particle Size. Acta Pharmaceutica, 62(3); 325–340

Shah, V. P., Y. Tsong, P. Sathe, and J. Liu (1998). In Vitro Dissolution Profile Comparison—Statistics and Analysis of the Similarity Factor, f2. Pharmaceutical research, 15(6); 889–896

Shruthi, K. and D. Thahera (2013). Preparation and Evaluation of Montelukast Sodium Chewable Tablets Using Modified Karaya Gum. Der Pharmacia Sinica, 4(4); 125–135

Singh, R., P. Saini, S. Mathur, G. Singh, and B. Lal (2010). Development and Validation of a RP HPLC Method for Estimation of Montelukast Sodium in Bulk and in Tablet Dosage Form. Indian Journal of Pharmaceutical Sciences, 72(2); 235

Singh, V. K., H. Kumar, A. K. Rajpoot, and S. R. Swain (2022). pKa and Partition Coefficient Determination of Montelukast Sodium by Spectrophotometric and HPLC Technique. Journal of Pharmaceutical Negative Results, 13(1); 2130–2140

Sinko, P. J. (2016). Martin’s Physical Pharmacy and Pharmaceutical Sciences. Lippincott Williams & Wilkins

Thibert, R., H. Mach, S.-D. Clas, D. R. Meisner, and E. B. Vadas (1996). Characterization of the Self-Association Properties of a Leukotriene D4 Receptor Antagonist, MK-0476. International Journal of Pharmaceutics, 134(1-2); 59–70

Torrado-Salmerón, C., V. Guarnizo-Herrero, J. Cerezo-Garreta, G. Torrado Durán, and S. Torrado Santiago (2019). Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats. Pharmaceutics, 11(12); 647

United States Pharmacopeial (2023). The United States Pharmacopeia (USP) 46 - National formulary (NF) 41. United Book Press, Inc

World Health Organization (2016). Generic Medicines: Interchangeability of WHO-Prequalified Generics. WHO Drug Information, 30(3); 370–375

Zaid, A. N., S. Natour, A. Qaddomi, and A. Abu Ghoush (2013). Formulation and In Vitro and In Vivo Evaluation of Film-Coated Montelukast Sodium Tablets Using Opadry® Yellow 20A82938 on an Industrial Scale. Drug Design, Development and Therapy, 7; 83–91


Poowadon Muenraya
Apichart Atipairin
Teerapol Srichana
Narumon Changsan
Neelam Balekar
Somchai Sawatdee (Primary Contact)
Muenraya, P. ., Atipairin, A., Srichana, T., Changsan, N., Balekar, N., & Sawatdee, S. (2024). Development of Pharmaceutical Equivalent Montelukast Sodium Immediate-Release, Film-Coated Tablets. Science and Technology Indonesia, 9(1), 43–58.

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