Evaluation of the physical properties of an orodispersible tablet containing melatonin and pyridoxine HCl (Vitamin B6)

Year 2024, Volume: 28 Issue: 6, 2137 - 2146, 28.06.2025

İsmail Aslan , Ahmet Arif Kurt

Abstract

Individuals deficient in melatonin are more prone to experiencing difficulties with sleep. The creation of an orally disintegrating tablet formulation of melatonin (MT) would enable a rapid and efficacious response to the population's needs. This formulation is suitable for all individuals, including the elderly and children, and is also preferred due to its pleasant taste. The text in question discusses the role of pyridoxine (PY) as a vital coenzyme involved in a number of physiological processes within the human body. The text emphasises the necessity of obtaining pyridoxine (PY) from external sources, given that the body is incapable of producing it autonomously. Moreover, the text delineates the formulation of a tablet containing both MT and PY, which is designed for convenient use and enhanced efficacy. Moreover, the text delineates the exhaustive testing regimen, which encompasses weight deviation, friability, disintegration time, moisture content, diameter and height measurements, and hardness tests, to ensure the physical stability of the manufactured tablets. The aforementioned tests demonstrated that the tablet satisfied the criteria set forth in the European Pharmacopoeia. The results of the physical tests conducted on the tablet containing MT and PY demonstrated that the values obtained were within the desired range and in accordance with the standards set forth in the European Pharmacopoeia. The mean hardness of the manufactured tablets was determined to be within the range of 27 ± 3.2 to 35 ± 1.5 Newton. In the friability test, the efficiency ratio was calculated to be 99.793. It is a widely accepted principle that the diameter and thickness of tablets should be 1/4. The results demonstrate that all ODTs exhibit this characteristic. The tablets were found to possess both hardness and friability, which ensures that the tablet remains stable and reduces losses to a minimum. The mean diameter of the tablets was found to be 7.08 ± 0.01 mm, with a mean height of 2.50 ± 0.01 mm. Furthermore, the mean diameter was determined to be 6.97 ± 0.01 mm, with a mean height of 3.21 ± 0.01 mm. The standardisation of the tablets was successfully accomplished. The disintegration test yielded an average disintegration time of between 20 and 28 seconds for the tablets in the oral cavity, which was deemed optimal. In conclusion, the text suggests that further evaluation through in vivo and in vitro tests could be conducted to further develop the formulation.

Keywords

Melatonin , pyridoxine (vitamin B6) , orodispersible tablet , formulation , physical analysis

References

• [1] Ayseli YI, Aytekin N, Buyukkayhan D, Aslan I, Ayseli MT. Food policy, nutrition and nutraceuticals in the prevention and management of COVID-19: Advice for healthcare professionals. Trends Food Sci Technol. 2020; 105: 186–199. https://doi.org/10.1016/j.tifs.2020.09.001
• [2] sodium Duman G, Aslan İ, Yekta Özer A, İnanç İ, Taralp, A. Liposome, gel and lipogelosome formulations containing hyaluronate. J Liposome Res. 2014; 24(4): 259–269. https://doi.org/10.3109/08982104.2014.907305
• [3] Kurt AA, Aslan I, Duman G. Next-Generation natural baby barrier cream formulations: physicochemical analysis and safety assessment. J Cosmetic Sci. 2021; 72(2):173-188.
• [4] Buran K. Design, synthesis, biological evaluation and docking, ADME studies of novel phenylsulfonyl piperazine analogues as α-amylase ınhibitors. Cumhuriyet Sci J 2024; 45(2): 268-273. https://doi.org/10.17776/csj.1401967
• [5] Aslan I, Kurt AA. In-vitro comparison release study of novel liposome and conventional formulation containing Rosmarinus officinalis extract. Curr Perspect Med Aroma Plants. 2021; 4(1): 13-21. https://doi.org/10.38093/cupmap.848115.
• [6] Buran K, İnan Y, Uba AI, Zengin G. Novel benzene sulfonamide-piperazine hybrid compounds: design, synthesis, antioxidant, enzyme inhibition activities and docking, ADME profiling studies. Z Naturforsch C J Biosci. 2024 Jun 24. https://doi.org/10.1515/znc-2024-0062
• [7] Aslan I, Kurt AA. Characterization and optimization of phytosome formulation containing alcohol-free umckalin from Pelargonium sidoides. Curr Perspect Med Aroma Plants. 2020; 3(1): 49-53. https://doi.org/10.38093/cupmap.737878
• [8] Ethemoglu MS, Seker FB, Akkaya H, Kilic E, Aslan I, Erdogan CS, Yilmaz B. Anticonvulsant activity of resveratrol-loaded liposomes in vivo. Neuroscience. (2017); 357: 12-19. https://doi.org/10.1016/j.neuroscience.2017.05.026
• [9] Günal MY, Ayla Ş, Bedri N, Beker MÇ, Çağlayan AB, Aslan I, Ozdemir EM, Yeşilada E, Kılıç Ü. The effects of topical liposomal resveratrol on incisional and excisional wound healing process. Turkderm Turk Arch Dermatol Venerol. 2019; 53(4): 128-134. http://doi.org/10.4274/turkderm.galenos.2019.82612
• [10] Gunal MY, Ayla S, Caglayan B, Beker MC, Bedri N, Aslan I, Ozdemir EM, Kilic E, Yesilada E. Can Carpobrotus edulis, heal incisional and excisional wounds on the skin?. Bratisl Lek Listy. 2021; 122(12): 912–917. https://doi.org/10.4149/BLL_2021_147
• [11] Yazici M, Duman G, Aslan I, Durucan A, Sahin F. The antifungal activity of liposomal ointment formulation of essential oil of Satureja hortensis. Curr Opin Biotechnol. 2011; 22: S108. https://doi.org/10.1016/j.copbio.2011.05.345
• [12] Ertas B, Onay IN, Yilmaz-Goler AM, Karademir-Yilmaz B, Aslan I, Cam ME. A novel high-efficiency transdermal patches for combinational therapy of Alzheimer's disease: Donepezil/vitamin B12-loaded nanofibers. J Drug Deliv Sci Technol. 2023; 89: 104963. https://doi.org/10.1016/j.jddst.2023.104963
• [13] Aslan I, Aytekin AF. Production and characterization of newly developed alcohol-free topical liposome gel transdermal drug delivery systems containing estradiol (E2)/ estriol (E3) for post-menopausal women. J Res Pharm. 2023; 27(5): 2190-2198. http://dx.doi.org/10.29228/jrp.499
• [14] Milliken RL, Quiten T, Andersen SK, Lamprou DA. Application of 3D printing in early phase development of pharmaceutical solid dosage forms. Int J Pharm. 2024; 653: 123902. https://doi.org/10.1016/j.ijpharm.2024.123902
• [15] Talib WH, Alsayed AR, Abuawad A, Daoud S, Mahmod AI. Melatonin in cancer treatment: Current knowledge and future opportunities. Molecules. 2021; 26(9):2506. https://doi.org/10.3390/molecules26092506.
• [16] Li T, Jiang S, Lu C, Yang W, Yang Z, Hu W, Yang Y. Melatonin: Another avenue for treating osteoporosis? J Pineal Res. 2019; 66(2): 1–12. https://doi.org/10.1111/jpi.12548.
• [17] Vlad RA, Antonoaea P, Todoran N, Muntean DL, Rédai EM, Silași OA, Tătaru A, Bîrsan M, Imre S, Ciurba A. Pharmacotechnical and analytical preformulation studies for cannabidiol orodispersible tablets. Saudi Pharm J. 2021;29(9):1029-1042. https://doi.org/10.1016/j.jsps.2021.07.012.
• [18] Cornila A, lurian S, Tomuta I, Profire A. Orally dispersible dosage forms for paediatric use: Current knowledge and development of nanostructure-based formulations. Pharmaceutics. 2022; 14(8): 1621. https://doi.org/10.3390/pharmaceutics14081621
• [19] Suarez-Sharp S, Li M, Duan J, Shah H, Seo P. Regulatory Experience with In Vivo In Vitro Correlations (IVIVC) in New Drug Applications. AAPS J. 2016; 18(6): 1379–1390. https://doi.org/10.1208/s12248 016-9966-2.
• [20] Bano D, Henge RM, Diab S, Goodwin DJ, Gorringe L, Ahmed M, Elkes R, Zomer S. Streamlining the development of an industrial dry granulation process for an immediate release tablet with systems modelling. Chem Eng Res Des. 2022; 178: 421–437. https://doi.org/10.1016/j.cherd.2021.12.033.
• [21] Dong QQ, Zhou MM, Lin X, Shen L, Feng Y. Differences in fundamental and functional properties of HPMC co-processed fillers prepared by fluid-bed coating and spray drying. Eur J Pharm Sci. 2018; 119(September 2017):147–158. https://doi.org/10.1016/j.ejps.2018.04.001.
• [22] Fayed MH, Aldawsari M F, AlAli AS, Alsaqr A, Almutairy B K, Aodah, A H, Helal, D A. Design-of experiment approach to quantify the effect of nano-sized silica on tableting properties of microcrystalline cellulose to facilitate direct compression tableting of binary blend containing a low dose drug. J Drug Deliv Sci Technol. 2022; 68: 103127. https://doi.org/10.1016/j.jddst.2022.103127.
• [23] Kuma A, Gernaey KV, Beer TD, Nopens I. Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production - A critical review. Eur J Pharm Biopharm. 2013; 85(3 PART B): 814–832. https://doi.org/10.1016/j.ejpb.2013.09.013.
• [24] Arndt OR, Baggio R, Adam AK, Harting J, Franceschinis E, Kleinebudde P. Impact of Different Dry and Wet Granulation Techniques on Granule and Tablet Properties: A Comparative Study. J Pharm Sci. 2018; 107(12): 3143–3152. https://doi.org/10.1016/j.xphs.2018.09.006.
• [25] Kristensen HG, Schaefer T. A Review on pharmaceutical compounds. Drug Dev Ind Pharm. 1987; 33(4): 37–45.
• [26] Chen P, Ansari MJ, Bokov D, Suksatan W, Rahman ML, Sarjad, MS. A review on key aspects of wet granulation process for continuous pharmaceutical manufacturing of solid dosage oral formulations. Arab J Chem. 2022; 15(2): 103598. https://doi.org/10.1016/j.arabjc.2021.103598.
• [27] Tamura H, Jozaki M, Tanabe M, Shirafuta Y, Mihara Y, Shinagawa M, Tamura I, Maekawa R, Sato S, Taketani T, Takasaki A, Reiter RJ, Sugino N. Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging. Int J Mol Sci. 2020;21(3):1135. https://doi.org/10.3390/ijms21031135
• [28] Ha M, Yoon D, Lee CY, Lee M, Kim YW, Lee JM. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res. 2024;76:e12949. https://doi.org/10.1111/jpi.12949.
• [29] Abdellah SA, Raverot V, Gal C, Guinobert I, Bardot V, Blondeau C, Claustrat B. Bioavailability of melatonin after administration of an oral prolonged-release tablet and an ımmediate-release sublingual spray in healthy male volunteers. Drugs RD. 2023; 23(3): 257–265. https://doi.org/10.1007/s40268-023 00431-9
• [30] Erland LE, Saxena PK. Melatonin natural health products and supplements: Presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281. http://dx.doi.org/10.5664/jcsm.6462