Natural Colorants Induce the Drug Release from Fast Dissolving Tablets

Esra Tariq Bayrakdar ¹, Sharad Visht ^1*, Duran Kala ², Saya Ameer ¹, Ahmed Hamdy ¹, Sawsan S. Al-Rawi ³, Samir Bhargava ⁴, Abhijeet Ojha ⁵

This study showed the impact of hydrophilic and hydrophobic colorants on drug release, crucial for improving palatability and therapeutic efficacy of fast dissolving tablets.

Abstract

Background: The use of fast-dissolving tablets (FDTs) presents a promising solution to the challenges faced by certain patient populations, such as children and geriatric patients. FDTs offer rapid disintegration and dissolution in the oral cavity, facilitating drug absorption without the need for water, thus improving dosing accuracy and therapeutic outcomes. This study investigated the impact of hydrophilic and hydrophobic colorants on drug release from FDTs, utilizing Fluorouracil (5-FU) as a model drug and various natural pigments as colorants. Method: The research methodology involved the extraction and characterization of pigments from Opuntia ficus-indica fruits and Nyctanthes arbor-tristis flowers, followed by pre-formulation studies of 5-FU and formulation of FDTs using a direct compression method. Various evaluation parameters were employed to assess the physicochemical properties and performance of the FDTs. Results: The results indicated that the yield of pigments extracted from the fruits and flowers met acceptable standards, with FTIR analysis confirming their chemical composition. Pre-formulation studies of 5-FU revealed its physical and chemical characteristics, ensuring compatibility with excipients. The FDTs exhibited desirable properties such as uniform thickness, drug content uniformity, and acceptable weight variation, hardness, and friability. Moreover, the FDTs demonstrated rapid disintegration, dissolution, and water absorption, along with satisfactory wetting time and in-vitro drug release profiles. Conclusion: FTIR and DSC studies confirmed the absence of drug-excipient interactions, ensuring the stability and integrity of the formulations. Overall, the incorporation of hydrophilic and hydrophobic colorants did not significantly affect the performance of the FDTs, indicating their suitability for use in pharmaceutical formulations.

Keywords: 5FU, Fast Dissolving Tablets, Hydrophilic Colorants, Hydrophobic Colorants, Pigment Extraction, FTIR Characterization

References

Arif, R., Visht, S., Yassen, A.O., Salih, S.S., 2024. Optimizing Fast-Dissolving Tablets of Ketotifen. Impact of Sodium Bicarbonate and Citric Acid in Formulation and Evaluation, Journal of Angiotherapy, 8(1), 1-11, 9379.

Aulton, M. and Taylor, K., 2013. Aulton's pharmaceutics. Edinburgh: Churchill Livingstone.

Ayenew, Z., Puri, V., Kumar, L. and Bansal, A., 2009. Trends in Pharmaceutical Taste Masking Technologies: A Patent Review. Recent Patents on Drug Delivery & Formulation, 3(1), pp.26-39.

Balata, G., Zidan, A., Abourehab, M. and Essa, E., 2016. Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution. Drug Design, Development and Therapy, Volume 10, pp.3211-3223.

Bharkatiya, M., Kitawat, S. and Gaur, K., 2018. Formulation and Characterization of Fast Dissolving Tablet of Salbutamol Sulphate. American Journal of Pharmacological Sciences, 6(1), pp.1-6.

Bhimte, N. and Tayade, P., 2007. Evaluation of microcrystalline cellulose prepared from sisal fibers as a tablet excipient: A technical note. AAPS PharmSciTech, 8(1), pp.E56-E62.

BI, Y., Sunada, H., Yonezawa, Y., Danjo, K., Otsuka, A. and Iida, K., 1996. Preparation and Evaluation of a Compressed Tablet Rapidly Disintegrating in the Oral Cavity. Chemical and Pharmaceutical Bulletin, 44(11), pp.2121-2127.

Bijauliya, R., Kannojia, P., Mishra, P., Singh, P. and Kannaujia, R., 2021. Pharmacognostical and Physiochemical Study on the Leaves of Nyctanthes arbor-tristis Linn. Journal of Drug Delivery and Therapeutics, 11(4), pp.30-34.

Bond, C., 1998. Comparison of Buccal and Oral Prochlorperazine in the Treatment of Dizziness Associated with Nausea and/or Vomiting. Current Medical Research and Opinion, 14(4), pp.203-212.

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

Fernández-López, J., Giménez, P., Angosto, J. and Moreno, J., 2022. A Process of Recovery of a Natural Yellow Colourant from Opuntia Fruits.

Hajjar, E., Cafiero, A. and Hanlon, J., 2007. Polypharmacy in elderly patients. The American Journal of Geriatric Pharmacotherapy, 5(4), pp.345-351.

Heer, S., Jindal, S., Mishra, G., Madan, J., Gupta, G., AWASTHI, D., Pinto, T., Dua, K. and Kulkarni, G., 2019. Formulation and characterization of oral rapid disintegrating tabletsof levocetirizine. Polymers in Medicine, 48(1), pp.31-40.

Hirlekar, R. and Kadam, V., 2009. Preformulation Study of the Inclusion Complex Irbesartan-β-Cyclodextrin. AAPS PharmSciTech, 10(1), pp.276-281.

Kozarewicz, P., 2014. Regulatory perspectives on acceptability testing of dosage forms in children. International Journal of Pharmaceutics, 469(2), pp.245-248.

Kulkarni, G.T. and Visht S., 2015:. Effect of some cations as counter ions on ulcer healing activity of glycyrrhetinic acid on male albino rats.. Int. J. Chem. Sci. , 13((3); ), pp. 1511-1521..

Kumar, M. Visht, S. Ali, S. Agarwal, S. Bhola, A. Preparation and evaluation of fast dissolving drug delivery system containing levocetrizine HCl.. Int. J. Pharm. Sci. , 2((3); ), pp. 109-111..

Mahant, S.A. Gaidhane, A.K. Dokrimare, N.A. Wadher, K.J. Lohiya, R.T. Umekar, M.J., 2020. Formulation and Evaluation of Fast Dissolving Tablet of Montelukast Sodium: Effect of Superdisintegrants. Scholars Academic Journal of Pharmacy, 09(02), pp.86-89.

Mansoureh Nazari Vishkaei, Mohamed Khadeer Ahamed Basheer, Amin Malik Shah Abdul Majid. (2019). Ethosomal formulation composed of standardized Orthosiphon stamineus extract and sophorolipid inhibits angiogenesis of melanoma in vivo. Angiotherapy, 1(2), pages 087–096.

Mehra, P., Kapoor, V., Gupta, N., Singh Rajpoot, D. and Sharma, N., 2021. Formulation Evaluation and Characterization of Fast Dissolving Tablets of Rofecoxib. Research Journal of Topical and Cosmetic Sciences, pp.60-64.

Mohan, A. and 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), p.57.

Nagar, P. Chauhan, K.S., I. Verma, M. Yasir, M. Khan, A. Sharma, R. Gupta, N. 2011. Orally disintegrating tablets : Formulation, preparation techniques and evaluation.. J. App Pharm Sci. , 01((04);), pp. 35-45..

Ngamwonglumlert, L., Devahastin, S. and Chiewchan, N., 2017. Natural colorants: Pigment stability and extraction yield enhancement via utilization of appropriate pretreatment and extraction methods. Critical Reviews in Food Science and Nutrition, 57(15), pp.3243-3259.

Open Library. 2022. European Pharmacopoeia 5th Ed. Main Volume 5.0, 2005 with Supplements 5.1 and 5.2 (European Pharmacopoeia) (July 2004 edition)

Panigrahi, R. and Behera, S., 2022. A Review On Fast Dissolving Tablets.Webmedcentral.com.

Parkash, V., Maan, S., Deepika, Yadav, S., Hemlata and Jogpal, V., 2011. Fast disintegrating tablets: Opportunity in drug delivery system. Journal of Advanced Pharmaceutical Technology & Research, 2(4), p.223.

Patel, Z., bhura, R. and Shah, S., 2020. Formulation optimization and evaluation of mouth dissolving film of ramosetron hydrochloride. International Journal of Current Pharmaceutical Research, pp.99-106.

Rai, R. Visht, S. Khan, A. Saini, P., 2012: . Formulation and Evaluation of 5-Fluorouracil Loaded Liposomes.. Int.J.Pharm.Phytopharmacol.Res. , 2((3);), pp. 222-228..

Ratner, P., Lim, J. and Georges, G., 2000. Comparison of once-daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and placebo in the treatment of seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology, 105(6), pp.1101-1107.

Rozhan Arif, Sharad Visht, Ali Omar, Sana Sirwan Salih. (2024). Optimizing Fast-Dissolving Tablets of Ketotifen: Impact of Sodium Bicarbonate and Citric Acid in Formulation and Evaluation, Journal of Angiotherapy, 8(1), 1-11, 9379

Sandhyarani, G., Srivastava,, P., Malviya,, R. and Visht, S., 2010. Formulation and evaluation of atenolol oral disintegrating tablets. World Journal of Pharmaceutical Research, pp.1073-1079.

Santos López, E., 2022. Colorant extraction from red prickly pear (Opuntia lasiacantha) for food application.

Scarano, P., Naviglio, D., Prigioniero, A., Tartaglia, M., Postiglione, A., Sciarrillo, R. and Guarino, C., 2020. Sustainability: Obtaining Natural Dyes from Waste Matrices Using the Prickly Pear Peels of Opuntia ficus-indica (L.) Miller. Agronomy, 10(4), p.528.

Sepúlveda, E., Sáenz, C., Aliaga, E. and Aceituno, C., 2007. Extraction and characterization of mucilage in Opuntia spp. Journal of Arid Environments, 68(4), pp.534-545.

Sharad Visht, Sana Sirwan Salih, Belan Azad Ibrahim et al., (2024). Advancing Therapeutic efficacy of Star Anise Oil with (Illicium verum) Nano-Emulsion Formulation, Journal of Angiotherapy, 8(1), 1-12, 9383

Sharma, D., 2012. Fast disintegrating tablets: a review on an emerging trend in novel oral drug delivery technology and new market opportunities. Journal of Drug Delivery and Therapeutics, 2(3).

Sharma, D., 2013. Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate for Respiratory Disorders. ISRN Pharmaceutics, 2013, pp.1-8.

Sharma, S., Sharma, N. and Gupta, G., 2010. Formulation of Fast-Dissolving Tablets of Promethazine Theoclate. Tropical Journal of Pharmaceutical Research, 9(5).

Shirsand, S., Suresh, S., Swamy, P., Para, M. and Nagendra Kumar, D., 2010. Formulation design of fast disintegrating tablets using disintegrant blends. Indian Journal of Pharmaceutical Sciences, 72(1), p.130.

Shrivastava, R. and Bharadwaj, A., 2018. Nyctanthes arbortristis an Important Medicinal Plant of Madhya Pradesh State - A Review. Pharmaceutical and Biosciences Journal, pp.10-15

Singh, J., Singh, A. and Singh, A., 2021. Nyctanthes arbor-tristis: a comprehensive review. World Journal of Current Medical and Pharmaceutical Research, pp.74-78.

Soni, T., Nagda, C., Gandhi, T. and Chotai, N., 2008. Development of Discriminating Method for Dissolution of Aceclofenac Marketed Formulations. Dissolution Technologies, 15(2), pp.31-35.

Tawashi, R. and Piccolo, J., 1972. Inhibited dissolution of drug crystals by certified water-soluble dyes: in vivo effect. Journal of Pharmaceutical Sciences, 61(11), pp.1857-1858.

Tripathi, S. and K. Tripathi, P., 2012. Evaluation of Anxiolytic Effect in Flowers of Nyctanthes arbor-tristis. Journal of Current Pharma Research, 3(1), pp.709-717.

Tumuluri, V., 2022. Pharmaceutical mini-tablets.

Überall, M. and Müller-Schwefe, G., 2011. S615 Sublingual fentanyl tablet for breakthrough cancer pain: dose titration in daily practice. European Journal of Pain Supplements, 5(1), pp.273-274.

Visht, S. and 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), pp.30-37.

Visht, S. and 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), pp.101-114.

Visht, S., Anjum, N. and Saini, A., 2018. Comparison of drug release: microparticles vs nanoparticles. International Research Journal of Pharmacy, 9(4), pp.52-58.

Wolska, E., Sznitowska, M., Krzeminska, K. and 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), p.664.

Zade, P.S., Kawtikwar, PS. Sakarkar, DM., 2022.  Formulation, Evaluation and Optimization of Fast Dissolving Tablet Containing Tizanidine Hydrochloride. International Journal of Pharm Tech Research, 1, 34-42. - References - Scientific Research Publishing.

Zhang, H., Zhang, J. and Streisand, J., 2002. Oral Mucosal Drug Delivery. Clinical Pharmacokinetics, 41(9), pp.661-680.