Angiogenesis, Inflammation & Therapeutics | Impact 0.1 (CiteScore) | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Optimizing Fast-Dissolving Tablets of Ketotifen: Impact of Sodium Bicarbonate and Citric Acid in Formulation and Evaluation

Rozhan Arif 1, Sharad Visht 1*, Ali Omar Yassen 1, Sana Sirwan Salih 1

+ Author Affiliations

Journal of Angiotherapy 8(1) 1-11 https://doi.org/10.25163/angiotherapy.819379

Submitted: 03 November 2023  Revised: 26 December 2023  Published: 19 January 2024 

Formulating ketotifen fast-dissolving tablets (FDT) tackled poor bioavailability challenges, emphasizing sodium bicarbonate's pivotal role for rapid tablet disintegration, highlighting FDT viability for asthmatic treatment.

Abstract


The research aimed to develop and assess fast-dissolving tablets (FDT) of ketotifen, a second-generation noncompetitive H1-receptor blocker, due to its poor oral bioavailability resulting from rapid first-pass effect (~50%) and poor solubility despite excellent permeability within the II-class of the biopharmaceutical classification system (BCS). The methodology involved formulating ketotifen with various excipients, including sodium bicarbonate, citric acid, menthol, polyvinyl pyrrolidone (PVP), aspartame, magnesium stearate, saccharin sodium, and dextrose. The combination of sodium bicarbonate and citric acid served as a fast-disintegrating agent by evolving carbon dioxide. Employing 23 factorial designs, the study assessed the impact of sodium bicarbonate (X1), citric acid (X2), and menthol (X3) on FDT performance. Batch A, exhibiting desirable characteristics, demonstrated weight variation (200±0.53), thickness (3.52±0.12 mm), hardness (2.87±0.23), friability (0.55±0.12), disintegration time (16±3 s), drug content uniformity (99.45±0.23), wetting time (3±1 s), and water absorption ratio (19.23±0.43). The primary contributor to fast tablet disintegration was identified as the high concentration of sodium bicarbonate rather than citric acid. All batches adhered to the Peppas Korsmeyer model, signifying Fickian Diffusion (Higuchi Matrix) as the drug release mechanism. In conclusion, the study underscored the pivotal role of sodium bicarbonate concentration in facilitating rapid tablet disintegration, emphasizing its significance over citric acid concentration.

Keywords: Fast-dissolving tablets (FDT), Ketotifen, Biopharmaceutical Classification System (BCS), Sodium Bicarbonate, Peppas Korsmeyer Model

References


Abd El Rasoul, S., & Shazly, G. A. (2017). Propafenone HCl fast dissolving tablets containing subliming agent prepared by direct compression method. Saudi Pharmaceutical Journal, 25(7), 1086-1092.

Alqahtani, M. S., Kazi, M., Alsenaidy, M. A., & Ahmad, M. Z. (2021). Advances in oral drug delivery. Frontiers in Pharmacology, 12, 618411.

Aungst, B. J. (2017). Optimizing oral bioavailability in drug discovery: an overview of design and testing strategies and formulation options. Journal of pharmaceutical sciences, 106(4), 921-929.

Ayenew, Z., Puri, V., Kumar, L., & Bansal, A. K. (2009). Trends in pharmaceutical taste masking technologies: a patent review. Recent patents on drug delivery & formulation, 3(1), 26-39.

Badgujar, B., & Mundada, A. (2011). The technologies used for developing orally disintegrating tablets: A review. Acta pharmaceutica, 61(2), 117-139.

 Bharkatiya et al., 2018 technology. International Journal of Pharmaceutical & Biological Archives, 1(1), 1-10.

Bharkatiya, M., Kitawat, S., & Gaur, K. (2018). Formulation and characterization of fast dissolving tablet of salbutamol sulphate. American Journal of Pharmacological Sciences, 6(1), 1-6.

Corveleyn, S., & Remon, J. P. (1997). Formulation and production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug. International journal of pharmaceutics, 152(2), 215-225.

Gandhi, I. T. (2022). The effect of treatment with the mast cell stabilizer ketotifen fumarate on chronic widespread pain in teenagers. McGill University (Canada).

Gupta, A., Mishra, A., Gupta, V., Bansal, P., Singh, R., & Singh, A. (2010). Recent trends of fast dissolving tablet-an overview of formulation

Gupta, R., Sharma, P., Garg, A., Soni, A., Sahu, A., Rai, S., Rai, S., & Shukla, A. (2013). Formulation and evaluation of herbal effervescent granules incorporated with Calliandra haematocephala leaves extract. Indo American Journal of Pharmaceutical Research, 3(6), 4366-4371.

Karimi Afshar, S., Abdorashidi, M., Dorkoosh, F. A., & Akbari Javar, H. (2022). Electrospun fibers: Versatile approaches for controlled release applications. International Journal of Polymer Science, 2022.

Kashyap, S., Sharma, V., & Singh, L. (2011). Fast disintegrating tablet: A boon to pediatric and geriatric. International Journal of Pharma Professional’s Research (IJPPR), 2(2), 266-274.

Masih, A., Kumar, A., Singh, S., & Tiwari, A. K. (2017). Fast dissolving tablets: A review. Int J Curr Pharm Res, 9(2), 8-18.

Mehra, P., Kapoor, V., Gupta, N., Rajpoot, D. S., & Sharma, N. (2021). Formulation evaluation and characterization of fast dissolving tablets of Rofecoxib. Research Journal of Topical and Cosmetic Sciences, 12(1), 60-64.

Mohamed, A.O., & Ali A. S. (2018). Preparation and Evaluation of Rapidly Dissolving Tablet of Telmisartan. Journal of advanced pharmacy research, 2 (3), 191-200

Mohan, A., & Gundamaraju, R. (2015). In vitro and in vivo evaluation of fast-dissolving tablets containing solid dispersion of lamotrigine. International journal of pharmaceutical investigation, 5(1), 57.

Muhammed, R.A., Yalman Othman, Z., Rashid Noaman, B., Visht, S., Jabbar, S., & Sirwan Salih, S. (2023). Innovations In Formulation And Evaluation Of Oral Fast Dissolving Film. Eurasian Journal of Science and Engineering, 9(2).

Mushtaq, M., Fazal, N., & Niaz, A. (2021). Correction to: Formulation and Evaluation of Fast-Disintegrating Tablets of Flurbiprofen and Metoclopramide. J Pharm Innov 16, 439–440. https://doi.org/10.1007/s12247-020-09461-1

Panigrahi, R., Chowdary, K., Mishra, G., Bhowmik, M., & Behera, S. (2012). Formulation of fast dissolving tablets of Lisinopril using combination of synthetic superdisintegrants. Asian Journal of Pharmacy and Technology, 2(3), 94-98.

Patel, Z., Bhura, R., & Shah, S. (2020). Formulation optimization and evaluation of mouth dissolving film of ramosetron hydrochloride. Int J Curr Pharm Sci, 12, 99-105.

Shah, R. B., Tawakkul, M. A., & Khan, M. A. (2008). Comparative evaluation of flow for pharmaceutical powders and granules. AAPS PharmSciTech, 9, 250-258.

Sharma, D. (2013). Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate for respiratory disorders. International Scholarly Research Notices, 2013.

Sharma, K., Agrawal, S., & Gupta, M. (2012). Development and validation of UV spectrophotometric method for the estimation of curcumin in bulk drug and pharmaceutical dosage forms. Int. J. Drug Dev. Res, 4(2), 375-380.

Siddiqui, M. N., Garg, G., & Sharma, P. K. (2010). Fast dissolving tablets: preparation, characterization and evaluation: an overview. International Journal of Pharmaceutical Sciences Review and Research, 4(2), 87-96.

Siraj, S. N., Kausar, S. H., Khan, G., & Khan, T. (2017). Formulation and evaluation of oral fast dissolving tablet of ondansetron hydrochloride by coprocess excipients. Journal of Drug Delivery and Therapeutics, 7(5), 102-108.

Sivapriya, S. (2018). Formulations and Evaluation of Oral Dispersible Tablets of Lafutidine by Direct Compression Method College of Pharmacy, Madurai Medical College, Madurai].

Soltani, S., Zakeri-Milani, P., Barzegar-Jalali, M., & Jelvehgari, M. (2017). Fabrication and in-vitro evaluation of ketotifen fumarate-loaded PLGA nanoparticles as a sustained delivery system. Iranian journal of pharmaceutical research: IJPR, 16(1), 22.

Srivastava, P., Malviya, R., & Visht, S. (2010). Formulation development and evaluation of atenolol fast disintegrating tablets for treatment of hypertension. JChrDD, 1(1), 36-42.

Truzzi, F., Tibaldi, C., Zhang, Y., Dinelli, G., & D′ Amen, E. (2021). An overview on dietary polyphenols and their biopharmaceutical classification system (BCS). International journal of molecular sciences, 22(11), 5514.

Tukaram, B. N., Rajagopalan, I. V., & Shartchandra, P. S. I. (2010). The effects of lactose, microcrystalline cellulose and dicalcium phosphate on swelling and erosion of compressed HPMC matrix tablets: texture analyzer. Iranian journal of pharmaceutical research: IJPR, 9(4), 349.

Visht, S., & Kulkarni, G. (2015). Studies on the Preparation and in vitro-in vivo Evaluation of Mucoadhesive Microspheres of Glycyrrhetinic Acid Isolated from Liquorice. Bangladesh Pharmaceutical Journal, 18(1), 30-37.

Visht, S., & T Kulkarni, G. (2016). Glycyrrhetinic Acid Ammonium Loaded Microspheres Using Colocasia esculenta and Bombax ceiba mucilages: In Vitro and In Vivo Characterization. Current Drug Therapy, 11(2), 101-114.

Wolska, E., Sznitowska, M., Krzeminska, K., & Ferreira Monteiro, M. (2020). Analytical techniques for the assessment of drug-lipid interactions and the active substance distribution in liquid dispersions of solid lipid microparticles (SLM) produced de novo and reconstituted from spray-dried powders. Pharmaceutics, 12(7), 664.

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