Floating tablets incorporating curcumin solid dispersion as a potential pharmaceutical dosage form for stomach cancer treatment

Duyen Thi My Huynh† Viet-Hung Tran† Minh-Ngoc T. Le Van-Hoa Huynh Duy Toan Pham   

Open Access   

Published:  Dec 24, 2022

DOI: 10.7324/JAPS.2023.114417

Curcumin, a well-known compound commonly used for stomach cancer treatment, possesses inadequate oral bioavailability due to its low water solubility and instability in the digestive-tract alkaline pH. To overcome these issues, this study formulated the curcumin solid dispersion (CSD) (to enhance curcumin solubility) and incorporated this solid dispersion in the floating tablet formula (to bypass the alkaline pH in the intestine). The tablets were optimized by varying numerous parameters including (1) the granulating solvent, (2) the binder excipient, (3) the type of gas-generating excipients, (4) the ratio of gas-generating excipients, (5) the type/amount of matrix generator, and (6) the tablet hardness. The product was then fully characterized in terms of floating potential, floating time, tablet integrity, curcumin solubility/dissolution profiles, long-term and accelerated stability study, in-vitro cytotoxicity, and other physicochemical properties. The best formula possesses a short floating potential of 35 ± 1 seconds, a long floating retention time of >8 hours, good tablet integrity during the floating duration, enhanced curcumin solubility/ dissolution profiles to >200 times, and perfect physicochemical stability for at least 2 years in the normal storage condition. Furthermore, the tablets reserve the curcumin cytotoxicity on the N87 stomach cell lines, with a better efficacy compared to the standard drug 5-FU. Finally, the tablets significantly potentiate and enhance the anticancer effect of 5-FU in a synergistic mechanism. Conclusively, the floating tablet incorporating the CSD could be a potential pharmaceutical product for stomach cancer treatment.

Keyword:     Floating tablet curcumin solid dispersion stability stomach cancer


Huynh DTM, Tran VH, Le MNT, Huynh VH, Pham DP. Floating tablets incorporating curcumin solid dispersion as a potential pharmaceutical dosage form for stomach cancer treatment. J Appl Pharm Sci, 2023; 13(04):240–250. https://doi.org/10.7324/JAPS.2023.114417

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci, 2009; 30(2):85-94; doi:10.1016/J.TIPS.2008.11.002. https://doi.org/10.1016/j.tips.2008.11.002

Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res, 2003; 23(1A):363-98.

Alshehri S, Imam SS, Hussain A, Altamimi MA, Alruwaili NB, Alotaibi F, Alanazi A, Shakeel F. Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: newer formulation techniques, current marketed scenario and patents. Drug Deliv, 2020; 27(1):1625-43; doi:10.1080/10717544.2020.1846638. https://doi.org/10.1080/10717544.2020.1846638

Becker D, Rigassi T, Bauer-Brandl A. Effectiveness of binders in wet granulation: a comparison using model formulations of different tabletability. Drug Dev Indus Pharm, 1997; 23(8):791-808; doi:10.3109/03639049709150550. https://doi.org/10.3109/03639049709150550

Chandira RM, Bhowmik D, Jayakar B. Formulation and evaluation of floating tablets of cefuroxime axetil. Int J Pharm Sci Res, 2011; 4:177-80.

Chowdary K, Hussainy S. Formulation and evaluation of floating tablets of gliclazide employing HPMC and carbopol. Int J Chem Sci, 2012; 10:1213-20.

Clinical Trials. Curcumin in preventing gastric cancer in patients with chronic atrophic gastritis or gastric intestinal metaplasia. n.d. Available via https:// clinicaltrials.gov/ ct2/ show/ NCT02782949? term = curcumin & cond = stomach + cancer & draw = 2 & rank = 1 (Accessed 19 July 2022).

Deb J, Ghosh A, Sen K, Paul P, Choudhury A. Formulation and evaluation of metformin HCl floating tablet using pectin as a natural polymer. Int Res J Pharm Sci, 2010; 01:0022.

European Medicines Agency. Stability testing of existing active ingredients and related finished products. n.d. Available via https://www. ema.europa.eu/en/stability-testing-existing-active-ingredients-related-finished-products (Accessed 5 November 2022).

Fuloria S, Mehta J, Chandel A, Sekar M, Rani NNIM, Begum MY, Subramaniyan V, Chidambaram K, Thangavelu L, Nordin R, Wu YS, Sathasivam KV, Lum PT, Meenakshi DU, Kumarasamy V, Azad AK, Fuloria NK. A comprehensive review on the therapeutic potential of Curcuma longa Linn. in relation to its major active constituent curcumin. Front Pharmacol, 2022; 13:820806; doi:10.3389/FPHAR.2022.820806/BIBTEX. https://doi.org/10.3389/fphar.2022.820806

Gerlier D, Thomasset N. Use of MTT colorimetric assay to measure cell activation. J Immunol Methods, 1986; 94(1-2):57-63; doi:10.1016/0022-1759(86)90215-2. https://doi.org/10.1016/0022-1759(86)90215-2

Hewlings SJ, Kalman DS. Curcumin: a review of its' effects on human health. Foods, 2017; 6(10); doi:10.3390/FOODS6100092. https://doi.org/10.3390/foods6100092

Huynh DTM, Le MNT, Tran VD, Pham DT. Antibacterial hydrogel containing Piper betel L. extract for acne treatment, an ex vivo investigation. Pharm Sci Asia, 2022; 49(4):372-80; doi:10.29090/ PSA.2022.04.22.061. https://doi.org/10.29090/psa.2022.04.22.061

Jaimini M, Rana A, Tanwar Y. Formulation and evaluation of famotidine floating tablets. Curr Drug Deliv, 2007; 4(1):51-5; doi:10.2174/156720107779314730. https://doi.org/10.2174/156720107779314730

Jivraj M, Martini LG, Thomson CM. An overview of the different excipients useful for the direct compression of tablets. Pharm Sci Technol Today, 2000; 3(2):58-63; doi:10.1016/S1461-5347(99)00237-0. https://doi.org/10.1016/S1461-5347(99)00237-0

Kanwar N, Kumar R, Sarwal A, Sinha VR. Preparation and evaluation of floating tablets of pregabalin. Drug Dev Indus Pharm, 2016; 42(4):654-60; doi:10.3109/03639045.2015.1062895. https://doi.org/10.3109/03639045.2015.1062895

Li X, Chen T, Xu L, Zhang Z, Li L, Chen H. Preparation of curcumin micelles and the in vitro and in vivo evaluation for cancer therapy. J Biomed Nanotechnol, 2014; 10(8):1458-68; doi:10.1166/JBN.2014.1840. https://doi.org/10.1166/jbn.2014.1840

Liu W, Zhai Y, Heng X, Che FY, Chen W, Sun D, Zhai G. Oral bioavailability of curcumin: problems and advancements. J Drug Targeting, 2016; 24(8):694-702; doi:10.3109/1061186X.2016.1157883. https://doi.org/10.3109/1061186X.2016.1157883

Liu X, Sun K, Song A, Zhang X, Zhang X, He X. Curcumin inhibits proliferation of gastric cancer cells by impairing ATP-sensitive potassium channel opening. World J Surg Oncol, 2014; 12(1); doi:10.1186/1477-7819-12-389. https://doi.org/10.1186/1477-7819-12-389

Nguyen NNT, Pham DT, Nguyen DT, Trinh TTL. Bilayer tablets with sustained-release metformin and immediate-release sitagliptin: preparation and in vitro/in vivo evaluation. J Pharm Investig, 2021a; 51(5):579-86; doi:10.1007/S40005-021-00533-Z. https://doi.org/10.1007/s40005-021-00533-z

Nguyen PH, Tran VD, Pham DT, Dao TNP, Dewey RS. Use of and attitudes towards herbal medicine during the COVID-19 pandemic: a cross-sectional study in Vietnam. Eur J Integr Med, 2021b; 44:101328; doi:10.1016/J.EUJIM.2021.101328. https://doi.org/10.1016/j.eujim.2021.101328

Nguyen TNN, Duy TP, Ngoc MT. Formulation and evaluation of low floating lag time metformin hydrochloride 500 mg sustained release floating tablet. Asian J Pharm (AJP), 2016; 10(04):497; doi:10.22377/AJP. V10I04.884. https://doi.org/10.22377/ajp

Nokhodchi A, Raja S, Patel P, Asare-Addo K. The role of oral controlled release matrix tablets in drug delivery systems. BioImpacts : BI, 2012; 2(4):175; doi:10.5681/BI.2012.027.

Pan-On S, Dilokthornsakul P, Tiyaboonchai W. Trends in advanced oral drug delivery system for curcumin: a systematic review. J Control Release, 2022; 348:335-45; doi:10.1016/J.JCONREL.2022.05.048. https://doi.org/10.1016/j.jconrel.2022.05.048

Pan-On S, Rujivipat S, Ounaroon A, Tiyaboonchai W. Development and characterization of clay facial mask containing turmeric extract solid dispersion. Drug Dev Indus Pharm, 2018; 44(4):590-97; doi:1 0.1080/03639045.2017.1405434. https://doi.org/10.1080/03639045.2017.1405434

Papich MG, Martinez MN. Applying Biopharmaceutical classification system (BCS) criteria to predict oral absorption of drugs in dogs: challenges and pitfalls. AAPS J, 2015; 17(4):948; doi:10.1208/ S12248-015-9743-7. https://doi.org/10.1208/s12248-015-9743-7

Pari L, Tewas D, Eckel J. Role of curcumin in health and disease. Arch Physiol Biochem, 2008; 114(2):127-49; doi:10.1080/13813450802033958. https://doi.org/10.1080/13813450802033958

Patel RK, Singh SK, Singh SB, Sheth NR, Gendle R. Development and characterization of curcumin loaded transfersome for transdermal delivery. J Pharm Sci Res, 2009; 1:71-80.

Perfetti G, Alphazan T, Wildeboer W, Meesters G. Thermo-physical characterization of pharmacoat((r)) 603, pharmacoat((r)) 615 and mowiol((R)) 4-98. J Therm Anal Calorim, 2012; 109; doi:10.1007/s10973- 011-1664-9. https://doi.org/10.1007/s10973-011-1664-9

Pham DT, Thao NTP, Thuy BTP, Tran VD, Nguyen TQC, Nguyen NNT. Silk fibroin hydrogel containing Sesbania sesban L. extract for rheumatoid arthritis treatment. Drug Deliv, 2022; 29(1):882-8; doi:10.1 080/10717544.2022.2050848. https://doi.org/10.1080/10717544.2022.2050848

Phothi T, Tunsophon S, Tiyaboonchai W, Khongsombat O. Effects of curcumin and γ-oryzanol solid dispersion on the brain of middle-aged rats. Biomed Rep, 2022; 17(1); doi:10.3892/BR.2022.1542. https://doi.org/10.3892/br.2022.1542

Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci, 2006; 29(3-4):278-87; doi:10.1016/J.EJPS.2006.04.016. https://doi.org/10.1016/j.ejps.2006.04.016

Prashar D, Khokra S, Purohit R, Sharma S. Curcumin: a potential bioactive agent. Res J Pharm Biol Chem Sci, 2011; 2:44-52. https://doi.org/10.1007/s11094-011-0538-6

Shishu NG, Aggarwal N. Bioavailability enhancement and targeting of stomach tumors using gastro-retentive floating drug delivery system of curcumin-'a technical note.' AAPS PharmSciTech, 2008; 9(3):810; doi:10.1208/S12249-008-9096-Y. https://doi.org/10.1208/s12249-008-9096-y

Someshwar K, Chithaluru K, Ramarao T, Kumar KK. Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride. Acta Pharm (Zagreb, Croatia), 2011; 61(2):217-26; doi:10.2478/V10007-011-0015-5. https://doi.org/10.2478/v10007-011-0015-5

Tadros MI. Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitro-in vivo evaluation in healthy human volunteers. Eur J Pharm Biopharm, 2010; 74(2):332-39; doi:10.1016/J.EJPB.2009.11.010. https://doi.org/10.1016/j.ejpb.2009.11.010

Tank D, Karan K, Gajera BY, Dave RH. Investigate the effect of solvents on wet granulation of microcrystalline cellulose using hydroxypropyl methylcellulose as a binder and evaluation of rheological and thermal characteristics of granules. Saudi Pharm J, 2018; 26(4):593- 602; doi:10.1016/J.JSPS.2018.02.007. https://doi.org/10.1016/j.jsps.2018.02.007

Tian F, Fan T, Zhang Y, Jiang Y, Zhang X. Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-ΚB signaling pathway in vitro and in vivo. Acta Biochim Biophys Sin, 2012; 44(10):847- 55; doi:10.1093/ABBS/GMS074. https://doi.org/10.1093/abbs/gms074

Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics, 2019; 11:193; doi:10.3390/PHARMACEUTICS11040193. https://doi.org/10.3390/pharmaceutics11040193

Tran VD, Tran VD, Pham DT, Cao TTN, Bahlol M, Dewey RS, Le MH, Nguyen VA. Perspectives on COVID-19 prevention and treatment using herbal medicine in Vietnam: a cross-sectional study. Ann Ig, 2022; 34(5); doi:10.7416/AI.2021.2484.

Vo CLN, Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm, 2013; 85(3 Pt B):799-813; doi:10.1016/J.EJPB.2013.09.007. https://doi.org/10.1016/j.ejpb.2013.09.007

Wook Huh H, Na YG, Kang HC, Kim M, Han M, Pham TMA, Lee H, Baek JS, Lee HK, Cho CW. Novel self-floating tablet for enhanced oral bioavailability of metformin based on cellulose. Int J Pharm, 2021; 592:120113; doi:10.1016/J.IJPHARM.2020.120113. https://doi.org/10.1016/j.ijpharm.2020.120113

Yang H, Huang S, Wei Y, Cao S, Pi C, Feng T, Liang J, Zhao L, Ren G. Curcumin enhances the anticancer effect of 5-fluorouracil against gastric cancer through down-regulation of COX-2 and NF- ΚB signaling pathways. J Cancer, 2017; 8(18):3697; doi:10.7150/JCA.20196. https://doi.org/10.7150/jca.20196

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