Gummies and gel tablets: New approaches to oral drug delivery

Abstract

Oral drug intake is accepted as the most preferred route of administration to reveal therapeutic effects in local and systemic diseases. The most important advantages of the oral route are that it is the most preferred route of administration in terms of not requiring specific sterility conditions, cost-effectiveness, ease of production of the dosage form, high patient compliance, and being non-invasively applicable. However, pediatric, geriatric and bedridden patients and disadvantaged patients who are dysphagic or mentally unable to adapt have difficulties using conventional oral dosage forms such as tablets or capsules. Alternative formulations, such as liquid dosage forms or orally dispersible tablets, have facilitated the administration of orally administered drugs and can relatively reduce problems related to dysphagia (difficulty swallowing). However, liquid dosage forms have the disadvantage of low stability in the long term. It is known that orodispersible tablets reduce patient compliance due to the taste of the active ingredient that cannot be suppressed and the drying sensation they leave in the mouth in the geriatric population with reduced saliva production. All these shortcomings increase the search for a new generation dosage form. Gummies and gel tablets are among the new-generation dosage forms introduced to the market as an alternative to conventional oral dosage forms and whose market share is expected to increase. Gummies and gel tablets do not require water or pleasant chewiness. Thanks to their advantages, such as exciting colour, odour and taste, an increase in patient acceptability has been observed compared to other oral dosage forms. This review mentions the advantages and disadvantages of oral administration, conventional oral dosage forms, detailed information about gummies and gel tablets, preparation methods, excipients used, current research and the place and future of these innovative dosage forms in the pharmaceutical industry.

Keywords

• Gummy
• gel tablet
• oral drug delivery
• pediatric
• geriatric

References

1. [1] Hedaya MA. Routes of drug administration. In: Dash AK, Singh S. (Eds). Pharmaceutics: Basic principles and application to pharmacy practice (2th ed). Elsevier Inc., Amsterdam, 2024, pp.537–554. https://doi.org/10.1016/B978-0-323-99796-6.00006-0.
2. [2] Mengdi S, Mingxiao C, Zhou F, Kehai L. Advanced research on extracellular vesicles based oral drug delivery systems. J Control Release. 2022;351:560-572. https://doi.org/10.1016/j.jconrel.2022.09.043.
3. [3] Alqahtani MS, Kazi M, Mohammad AA, Muhammad ZA.Advances in oral drug delivery. Front Pharmacol. 2021;12:618411. https://doi.org/10.3389/fphar.2021.618411.
4. [4] Susan H, Ellen M, Jennifer JS, Simon K. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomed Nanotechnol Biol Med. 2015;11(5):1117-1132. https://doi.org/10.1016/j.nano.2015.02.018.
5. [5] Shammy J, Kamya J, Ghanshyam DG, Rajeev G, Rajendra A. Gastroretentive floating tablets: An investigation of excipients effect on tablet properties. J Res Pharm. 2016;20(2):100-110. https://doi.org/10.12991/mpj.20162018166.
6. [6] Torres-Suárez AI, Martín-Sabroso C, Fraguas-Sánchez AI, Rojo MÁ, Garrosa M, Fernández-Carballido A. (2024). Design of dosage forms: Influences of anatomy and administration routes. In Dosage Forms, Formulation Developments and Regulations (pp. 183-221). Academic Press. https://doi.org/10.1016/B978-0-323-91817-6.00010-3
7. [7] Viswanathan P, Muralidaran Y, Ragavan G. Challenges in oral drug delivery: A nano-based strategy to overcome. In: Ecaterina A, Alexandru MG, (Eds). Nanostructures for oral medicine. Elsevier Inc., Amsterdam, 2017, pp.173-201. https://doi.org/10.1016/B978-0-323-47720-8.00008-0.
8. [8] Siddiqui M, Garg G, Sharma PK. A short review on “a novel approach in oral fast dissolving drug delivery system and their patents”. Adv Biol Res. 2011;5(6):291-303.

9. [9] Mrsny RJ. Oral drug delivery research in Europe. J Control Release. 2012;161(2):247-253. https://doi.org/10.1016/j.jconrel.2012.01.017.
10. [10] Gabor F, Fillafer C, Neutsch L, Ratzinger G, Wirth M. Improving oral delivery. Handb Exp Pharmacol. 2010;(197):345- https://doi.org/10.1007/978-3-642-00477-3_12
11. [11] Borges AF, Silva C, Coelho JF, Simões, S. Oral films: Current status and future perspectives II—Intellectual property, technologies and market needs. J Control Release. 2015; 206: 108-121. https://doi.org/10.1016/j.jconrel.2015.03.012
12. [12] Hua S. Advances in oral drug delivery for regional targeting in the gastrointestinal tract-influence of physiological, pathophysiological and pharmaceutical factors. Front Pharmacol. 2020;11:524. https://doi.org/10.3389/fphar.2020.00524
13. [13] Cade BF, Jean K, Long VL, Cameron LN, Hariharasudhan DC, Tejal AD. Micro/nanofabricated platforms for oral drug delivery. J Control Release. 2015;219:431-444. https://doi.org/10.1016/j.jconrel.2015.07.033.
14. [14] Yuan L, Honglian G, Rengui X. Wei C. Smart intraoral systems for advanced drug delivery. MedComm. 2022;1(2):19. https://doi.org/10.1002/mba2.19.
15. [15] Jiang O, Zhongyang Z, Bo D, Jinggong L, Liqiang W, Haijun L, Seyoung K, Shuying C, Yongjiang L, Alexey VY, Xiangang H, Wei C, Yuhan L, Wei T. Oral drug delivery platforms for biomedical applications. Mater Today. 2023;62:296-326. https://doi.org/10.1016/j.mattod.2023.01.002.
16. [16] Anja V, Gabrijela T, Željko K, Zoran N. Characterisation of biodegradable pectin aerogels and their potential use as drug carriers. Carbohydr Polym. 2014;113:272-278. https://doi.org/10.1016/j.carbpol.2014.06.054.
17. [17] Morten JD, Magnus NH, Kurt ID. Soft, chewable gelatin-based pharmaceutical oral formulations: A technical approach. Pharm Dev Technol. 2018;23(5):504-511. https://doi.org/10.1080/10837450.2017.1332642.
18. [18] Awis Sukarni MS, Nur Anis NMS, Qamar UA, Mohd MM, Nazreen CR,Juzaili A. Soft-chewable paracetamol tablets by melt granulation method: Formulation and characterization. J Pharm Bioallied Sci. 2021;13(3):312-316. https://doi.org/10.4103/jpbs.JPBS_783_20.
19. [19] Brown TD, Whitehead KA, Mitragotri S. Materials for oral delivery of proteins and peptides. Nat Rev Mater. 2020;5(2):127-148. https://doi.org/10.1038/s41578-019-0156-6.
20. [20] Ju-Young K, Sang-hyub K, Yun-Seok R, Chun-Woong P, Eun-Seok P. Preparation of hydroxypropylmethyl cellulose-based porous matrix for gastroretentive delivery of gabapentin using the freeze-drying method. Cellulose. 2013;20:3143-3154. https://doi.org/10.1007/s10570-013-0048-7.
21. [21] Nguyen S, Hiorth M. Advanced drug delivery systems for local treatment of the oral cavity. Ther Deliv. 2015;6(5):595-608. https://doi.org/10.4155/tde.15.5.
22. [22] Rathbone MJ, Senel S, Pather I. Overview of oral mucosal delivery. In: Rathbone MJ, Senel S, Pather I, (Eds). Oral mucosal drug delivery and therapy. Springer, Boston, 2015, pp.17-19. https://doi.org/10.1007/978-1-4899-7558-4_2.
23. [23] Majumder J, Taratula O, Minko T. Nanocarrier-based systems for targeted and site specific therapeutic delivery. Adv Drug Deliv Rev. 2019;144:57-77. https://doi.org/10.1016/j.addr.2019.07.010.
24. [24] Chen C, Beloqui A, Xu Y. Oral nanomedicine biointeractions in the gastrointestinal tract in health and disease. Adv Drug Deliv Rev. 2023;203:115117. https://doi.org/10.1016/j.addr.2023.115117.
25. [25] Leal J, Smyth HD, Ghosh D. Physicochemical properties of mucus and their impact on transmucosal drug delivery. Int J Pharm. 2017;532(1): 555-572. https://doi.org/10.1016/j.ijpharm.2017.09.018 .
26. [26] Jenny KWL, Yingying X, Alan W, Ian CKW. Oral transmucosal drug delivery for pediatric use. Adv Drug Deliv Rev. 2014;73:50-62. https://doi.org/10.1016/j.addr.2013.08.011.
27. [27] Al-Madhagi WM, Alshargabi A, Alzomor AKY, Sharhan O. Formulation of new chewable oral dosage forms of meclizine and pyridoxine hydrochloride. Adv Pharmacol Pharm Sci. 2023;29: 2023:5512379. https://doi.org/10.1155/2023/5512379 .
28. [28] Jie L, Hongli D, Qin Q, Zhipeng T, Fengxu G, Xiaofang Z, Xing Z. Advances in oral drug delivery systems: Challenges and opportunities. Pharmaceutics. 2023;15(2):484. https://doi.org/10.3390/pharmaceutics15020484.
29. [29] Homayun B, Lin X, Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics. 2019;11(3):129. https://doi.org/10.3390/pharmaceutics11030129.
30. [30] Yamashita F, Hashida M. Pharmacokinetic considerations for targeted drug delivery. Adv Drug Deliv Rev. 2013;65(1): 139-147. https://doi.org/10.1016/j.addr.2012.11.006 .
31. [31] Mohammadzadeh R, Javadzadeh Y. An overview on oral drug delivery via nano-based formulations. Pharm Biomed Res. 2018;4(1):1-7. https://doi.org/10.18502/pbr.v4i1.139.
32. [32] Elena M, Simon M, Jean-Christophe L. Oral delivery of macromolecular drugs: Where we are after almost 100 years of attempts. Adv Drug Deliv Rev. 2016;101:108-121. https://doi.org/10.1016/j.addr.2016.01.010.
33. [33] Martin JO, Ludovic B, Silvia M, Caitriona MO. Intestinal delivery of non-viral gene therapeutics: physiological barriers and preclinical models. Drug Discov Today. 2011;16(5-6):203-218. https://doi.org/10.1016/j.drudis.2011.01.003 .
34. [34] Carmen MG, Reece M, Lasse HET, Mahdi G, Anja B. Smart pills and drug delivery devices enabling next generation oral dosage forms. J Control Release. 2023;364:227-245. https://doi.org/10.1016/j.jconrel.2023.10.041.
35. [35] Utkarsh B, Tithi B, Saptarshi M. Oral drug delivery: conventional to long acting new-age designs. Eur J Pharm Biopharm. 2021;162:23-42. https://doi.org/10.1016/j.ejpb.2021.02.008.
36. [36] Stielow M, Witczyńska A, Kubryń N, Fijałkowski Ł, Nowaczyk J, Nowaczyk A. The Bioavailability of drugs—the current state of knowledge. Molecules. 2023; 28(24):8038. https://doi.org/10.3390/molecules28248038 .
37. [37] Hoag S. Capsules dosage form: formulation and manufacturing considerations. In: Qiu Y, Chen Y, Zhang GGZ, Yu L, Rao VM, (Eds). Developing solid oral dosage forms (2th ed). Elsevier Inc., Amsterdam, 2017, pp.723-747. https://doi.org/10.1016/B978-0-12-802447-8.00027-3.
38. [38] Mittal AD, Rahul ML, Sushrut PM, Tarul DM, Tasnim F, Alia A, Hyung KL, Michael AR, S Narasimha M. Excipient stability in oral solid dosage forms: A review. AAPS Pharm Sci Tech. 2018;19:12-26. https://doi.org/10.1208/s12249-017-0864-4.
39. [39] Rane SS, Moe D. Tablets and other solid dosage forms for systemic oral mucosal drug delivery. In: Oral Mucosal Drug Delivery and Therapy, 2015, pp.169-205. https://doi.org/10.1007/978-1-4899-7558-4_8
40. [40] Nyamweya N. Kimani S. Chewable tablets: A review of formulation considerations. Pharm Tech. 2020;44(11):38-44.
41. [41] Gupta A, Chidambaram N, Khan MA. An index for evaluating difficulty of chewing Index for chewable tablets. Drug Dev Ind Pharm. 2015;41(2):239-243. https://doi.org/10.3109/03639045.2013.858736.
42. [42] Kirsch K, Hanke U, Weitschies W. An overview of intestinal wafers for oral drug delivery. Eur J Pharm Biopharm. 2017;114:135-144. https://doi.org/10.1016/j.ejpb.2017.01.003.
43. [43] Kean EA, Adeleke OA. Orally disintegrating drug carriers for paediatric pharmacotherapy. Eur J Pharm Sci. 2023;182:106377. https://doi.org/10.1016/j.ejps.2023.106377.
44. [44] Costa JSR, Oliveira CK, Oliveira-Nascimento L. A mini-review on drug delivery through wafer technology: Formulation and manufacturing of buccal and oral lyophilizates. J Adv Res. 2019;20:33-41. https://doi.org/10.1016/j.jare.2019.04.010.
45. [45] Kar M, Chourasiya Y, Maheshwari R, Tekade RK. Current developments in excipient science: Implication of quantitative selection of each excipient in product development. In: Tekade RK, (Eds). Basic fundamentals of drug delivery. Elsevier Inc., Amsterdam, 2019, pp.29-83. https://doi.org/10.1016/B978-0-12-817909-3.00002-9.
46. [46] Farnoosh K, Babur ZC, Milan DA, Joshua SB. Novel films for drug delivery via the buccal mucosa using model soluble and insoluble drugs. Drug Dev Ind Pharm. 2012;38(10):1207-1220. https://doi.org/10.3109/03639045.2011.644294.
47. [47] Costa JSR, de Oliveira Cruvinel K, Oliveira-Nascimento L. A mini-review on drug delivery through wafer technology: Formulation and manufacturing of buccal and oral lyophilizates. J Adv Res. 2019;20: 33-41. https://doi.org/10.1016/j.jare.2019.04.010 .
48. [48] Matulyte I, Akvile M, Saule V, Jurga B. The effect of myristica fragrans on texture properties and shelf-life of innovative chewable gel tablets. Pharmaceutics. 2021;13(2):238. https://doi.org/10.3390/pharmaceutics13020238.
49. [49] Matulyte I, Marksa M, Bernatoniene J. Development of innovative chewable gel tablets containing nutmeg essential oil microcapsules and their physical properties evaluation. Pharmaceutics. 2021;13(6):873. https://doi.org/10.3390/pharmaceutics13060873.
50. [50] Surbhi R, Nitin D. Regulatory control over chewable gels and current challenges. Ann Phytomed. 2023;12(1):212-219. http://dx.doi.org/10.54085/ap.2023.12.1.83.
51. [51] Gonzalez MA, Ramírez-Rigo MV, Gonzalez Vidal NL. Nanoparticle-based chewable gels of praziquantel. Pharm Dev Technol. 2023;28(1):143-151. https://doi.org/10.1080/10837450.2023.2169455.
52. [52] Chunxiao Z, Yang T, Enhui Z, Xiang G, Hui Z, Nan L, Xiaolu H, Yong S, Zengming W, Aiping Z. Semisolid extrusion 3D printing of propranolol hydrochloride gummy chewable tablets: an innovative approach to prepare personalized medicine for pediatrics. AAPS PharmSciTech. 2022;23(166). https://doi.org/10.1208/s12249-022-02304-x
53. [53] Bing Y, Seyed MD, Raheleh R, Younas D, Ted WD, Toan VP, Paul AO, Rupa HD, Alireza A. Improvement of vitamin C stability in vitamin gummies by encapsulation in casein gel. Food Hydrocoll. 2021;113:106414. https://doi.org/10.1016/j.foodhyd.2020.106414.
54. [54] Thivya P, Durgadevi M, Sinija VRN. Biodegradable medicated chewing gum: A modernized system for delivering bioactive compounds. Future Foods. 2021;4:100054. https://doi.org/10.1016/j.fufo.2021.100054.
55. [55] Yang X, Wang G, Zhang X. Release kinetics of catechins from chewing gum. J Pharm Sci. 2004;93(2):293-299. https://doi.org/10.1002/jps.10564.
56. [56] Lauretta M, Ubaldo C, Alain N, Pascal G, Guy V. Evaluation of accelerated stability test conditions for medicated chewing gums. Drug Dev Ind Pharm. 2013;39(10):1500-1507. https://doi.org/10.3109/03639045.2012.704380.
57. [57] Rani KC, Jayani NIE, Feneke F, Melanda S. Preparation and evaluation of gelatin and pectin-based Moringa oleifera chewable-gummy tablets. IOP Conf. Ser. Earth Environ Sci. 2021;913. https://doi.org/10.1088/1755-1315/913/1/012082.
58. [58] Emma AK, Oluwatoyin AA, A child-friendly anti-infective gummy formulation: Design, physicochemical, micromechanical, and taste sensory evaluation. Drug Deliv Transl Res. 2023;14(15):1-19. https://doi.org/10.1007/s13346-023-01464-y.
59. [59] Sajed A, Marjan G, Hamed H, Leila R. Improvement in the stability of betanin by liposomal nanocarriers: Its application in gummy candy as a food model. Food Chem. 2018;256:156-162. https://doi.org/10.1016/j.foodchem.2018.02.114.
60. [60] Čižauskaitė U, Jakubaitytė G, Žitkevičius V, Kasparavičienė G. Natural ingredients-based gummy bear composition designed according to texture analysis and sensory evaluation in vivo. Molecules. 2019;24(7):1442. https://doi.org/10.3390/molecules24071442.
61. [61] Jurga AK, Inga M, Mindaugas M, Jurga B. Nutmeg essential oil, red clover, and liquorice extracts microencapsulation method selection for the release of active compounds from gel tablets of different bases. Pharmaceutics. 2023;15(3):949. https://doi.org/10.3390/pharmaceutics15030949.
62. [62] Sruthi S, Umesh KS, Arathy SA. Pharmaceutical Jellies: A novel way of drug delivery. J Pharm Sci. 2020;12(7):904-909
63. [63] Khade K, Kulkarni N, Bhamare V, Amrutkar Rakesh. Formulation, development and characterization of oral jelly to improve therapeutic effectiveness. Int J Pharm Qual Assur. 2024;15(2):1023-1034. https://doi.org/10.25258/ijpqa.15.2.73.
64. [64] Saha D, Bhattacharya S. Hydrocolloids as thickening and gelling agents in food: A critical review. J Food Sci Technol. 2010;47(6):587-97. https://doi.org/10.1007/s13197-010-0162-6.
65. [65] Satyanarayana DA, Parthasarathi KK, Shivakumar HG. Gels and jellies as a dosage form for dysphagia patients: a review. Curr Drug Ther. 2011;6(2): 79-86. https://doi.org/10.2174/157488511795304921 .
66. [66] Tarahi M, Tahmouzi S, Kianiani MR, Ezzati S, Hedayati S, Niakousari M. Current Innovations in the development of functional gummy candies. Foods. 2024;13(1): 76. https://doi.org/10.3390/foods13010076 .
67. [67] Rowe RC, Sheskey P, Quinn M. Handbook of Pharmaceutical Excipients (8th ed). London UK; Pharmaceutical Press;2009;795-797, 906-910.
68. [68] Prakash K. Formulation development and evaluation of novel oral jellies of carbamazepine using pectin, guar gum, and gellan gum. Asian J Pharm. 2014;8(4):241-249.
69. [69] Galande AD, Khurana NA, Mutalik S. Pediatric dosage forms-challenges and recent developments: A critical review. J Appl Pharm Sci. 2020;10(7):155-166. https://doi.org/10.7324/JAPS.2020.10718.
70. [70] Niam MLQ, Amin RS, Utami N, Wahyuni AS. Formulation of dietary supplement chewable gummy with bastard cedar leaves (Guazuma Ulmifolia), senna leaves (Cassia Angustifolia) and lime extracts using a simplex lattice design. In Proceedings of the International Conference on Sustainable Innovation on Health Sciences and Nursing ICOSI-HSN. Atlantis Press, Amsterdam. 2022: pp.122-135. https://doi.org/10.2991/978-94-6463-070-1_17.
71. [71] Helena HM, David RG, M Alejandro F, Marc SP, Pilar PL, Encarnación GM, Enrique A. 3D printed gummies: Personalized drug dosage in a safe and appealing way. Int J Pharm. 2020;587:119687. https://doi.org/10.1016/j.ijpharm.2020.119687.
72. [72] GrandViewResearch. Gummy Market Size. Available online: https://www.grandviewresearch.com/industry-analysis/gummy-market-report# (accessed Jun 29, 2024).
73. [73] Tuna B, Stine WA, Magnus NH, Kurt ID. Physical and functional properties of plant-based pre-emulsified chewable gels for the oral delivery of nutraceuticals. Appl Food Res. 2022;2(2):100225. https://doi.org/10.1016/j.afres.2022.100225.
74. [74] Kadhim ZM, Ali WK. Preparation and evaluation of granisetron chewable pediatric oral jelly. J Drug Deliv Sci Technol. 2019;9:348-351. https://doi.org/10.25258/ijddt.v9i3.4.
75. [75] Elena B, Modestas R, Vita L, Paulina Z, Jurga B, Valdas J, Liudas I, Daiva Z, Dovile K, Pranas V. Joana B,Vesta NS, Grazina J. Development of antimicrobial gummy candies with addition of bovine colostrum, essential oils and probiotics. Int J Food Sci Tech. 2018;53(5):1227-1235. https://doi.org/10.1111/ijfs.13701.
76. [76] Sabri LA, Khasraghi AH, Sulaiman HT. Preparation and evaluation of oral soft chewable jelly containing flurbiprofen. J Adv Pharm Technol Res. 2022;13(4);306-311. https://doi.org/10.4103/japtr.japtr_465_22.
77. [77] L’il Critters. Available online: https://www.lilcritters.com (accessed Oct 15, 2024).
78. [78] Centrum. Available online: https://www.centrum.com (accessed Oct 15, 2024).
79. [79] Vitafusion. Available online: https://www.vitafusion.com/ (accessed Oct 15, 2024).
80. [80] One A Day®. Available online: https://www.oneaday.com/ (accessed Oct 15, 2024).
81. [81] SmartyPants. Available online: https://www.smartypantsvitamins.com/ (accessed Oct 15, 2024).
82. [82] Nordic Naturals. Available online: https://www.nordicnaturals.uk/ (accessed Oct 15, 2024). [83] Queisser Pharma. Available online: https://www.queisser.com/ (accessed Oct 15, 2024).