Acidity, often experienced as heartburn or a burning sensation in the chest, is a common symptom of gastroesophageal reflux disease (GERD)?a condition that affects millions worldwide. While conventional medicines are available, many come with side effects or don?t always provide complete relief. That?s where herbal remedies, combined with modern drug delivery technologies, are beginning to show great promise.One such innovation is herbal sublingual films (HSFs)?thin strips that dissolve under the tongue, allowing herbs to quickly enter the bloodstream without going through the digestive system. This not only speeds up relief but also makes it easier for people who have trouble swallowing pills.This article takes a closer look at how these herbal films are made, what ingredients they contain (such as licorice, amla, and aloe vera), and how they work. It also discusses the science behind their design?like the use of natural polymers and specialized techniques to ensure strength, flexibility, and quick drug release.Additionally, the review compares how fast and effectively herbal extracts are absorbed when taken under the tongue versus traditional oral methods. It also explores exciting future directions?like combining multiple herbs, using smart materials, and incorporating artificial intelligence to fine-tune the film formulation.With continued research and proper safety checks, herbal sublingual films could soon become a trusted and widely used solution for managing acidity and related digestive issues?bringing the best of both herbal wisdom and modern science together.
Keywords
Herbal sublingual films, GERD, Acidity treatment, Novel drug delivery system (NDDS), Sublingual absorption, Herbal formulation, Fast-dissolving films
Introduction
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Gastroesophageal reflux disease (GERD) is a widespread gastrointestinal (GI) condition and is among the most frequently observed disorders in clinical settings [1,2]. The hallmark symptoms of GERD include heartburn and acid reflux, which are commonly reported by affected individuals [3,4]. Numerous studies conducted worldwide have investigated its occurrence and found a particularly high prevalence in Western countries [5]. In the United States, it has been documented that around 44% of adults report experiencing heartburn at least once per month, 14% on a weekly basis, and 7% suffer from it daily [6].Novel Drug Delivery SystemA Novel Drug Delivery System (NDDS) encompasses a range of innovative methods, formulations, and technologies developed to facilitate the controlled and targeted transport of therapeutic agents within the body, with the aim of achieving desired clinical outcomes. These systems are designed to ensure that drugs reach specific targets efficiently while maintaining effective therapeutic levels [7]. Ongoing research in this field has focused on the development of platforms such as liposomes, nanoparticles, niosomes, transdermal systems, implants, microencapsulation, and polymer-based carriers [7]. Among these, sublingual drug delivery has gained attention for its ability to offer fast absorption and bypass the gastrointestinal tract and liver metabolism. The effectiveness of sublingual administration depends on several factors, including the chemical properties of the drug, the formulation design, and the permeability of the sublingual mucosa [8]. This review primarily addresses the drug characteristics and formulation strategies necessary for effective sublingual delivery. When administered via this route, the drug is placed under the tongue and absorbed directly into the bloodstream through the tissues located beneath the tongue’s surface [9].Role of Herbal Medicine in Gastrointestinal Disorders Polyphenols, a group of plant-derived compounds, are widely recognized for their antioxidant capacity and potential health-promoting effects. A significant subgroup of these compounds, flavonoids, is abundantly found in various fruits, vegetables, teas, and medicinal herbs. Evidence suggests that both polyphenols and flavonoids may play a beneficial role in the management of GERD by reducing inflammation, counteracting oxidative stress, and enhancing mucosal protection [10,11]. When integrated into diet or therapeutic strategies, these naturally occurring antioxidants may complement conventional GERD treatments by enhancing efficacy and minimizing side effects. The strong anti-inflammatory and antioxidant actions of flavonoids make them particularly promising for GERD therapy. Research has indicated that oxidative stress is a major factor in mucosal injury and inflammation, which in turn worsens GERD symptoms [12]. Plant-based antioxidant compounds like flavonoids and polyphenols may help alleviate GERD symptoms by mitigating oxidative stress within the esophageal lining [13,14]. For instance, common foods such as onions and apples, rich in the flavonoid quercetin, have demonstrated the ability to reduce esophageal inflammation and suppress pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) [13,14].
2.Concept of Sublingual Drug Delivery System
[Fig1]: Sublingual Drug Delivery System [15]
In below [Fig2], The oral mucosa is composed of squamous epithelial cells and contains mucous glands. The structure of the buccal and sublingual mucosal tissues is similar in nature. For a drug to be effectively absorbed via the sublingual route, it must permeate through the buccal mucous membrane, primarily through a diffusion-driven process such as osmosis, which plays a key role in controlling both intestinal and sublingual retention of the drug [16].
Mechanism of drug absorption from the sublingual [16].
Reference
Dent J, El-Serag HB, Wallander MA, Johansson S. Epide miology of gastro-oesophageal reflux disease: a systematic review. Gut 2005; 54: 710-717
Holtmann G. Reflux disease: the disorder of the third millen nium. Eur J Gastroenterol Hepatol 2001; 13 Suppl 1: S5-S11
Isolauri J, Laippala P. Prevalence of symptoms suggestive of gastro-oesophageal reflux disease in an adult population. Ann Med 1995; 27: 67-70
Kennedy T, Jones R. The prevalence of gastro-oesophageal reflux symptoms in a UK population and the consultation be haviour of patients with these symptoms. Aliment Pharmacol Ther 2000; 14: 1589-1594
Mahadeva S, Raman MC, Ford AC, Follows M, Axon AT, Goh KL, Moayyedi P. Gastro-oesophageal reflux is more prevalent in Western dyspeptics: a prospective comparison of British and South-East Asian patients with dyspepsia. Aliment Phar macol Ther 2005; 21: 1483-1490
Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minne sota. Gastroenterology 1997; 112: 1448-1456
Delivery System Handbook for Personal Care and Cosmetic Products: Technology, Applications, and Formulations, Edited by Meyer R.R., Ed. William Andrew Publishing, Norwich, N.Y., USA. 2005. Winterhalter M, Hilty C, Bezrukov S M, Nardin C, Meier W, Fournier D. Controlling membrane permeability with bacterial porins. Applications to encapsulated enzymes. Talanta Arora N., Agarwal S., et al., IJPSDR, 2012; 4(3) : 168-182.
Ghatmale, R., & Pathan, V. T. (2023). An overview of sublingual routes for drug delivery & their application. International journal of current research and innovations in pharma sciences, 1(2), 78- 83.
De Jesús Valle, M. J., Zarzuelo Castañeda, A., Maderuelo, C., Cencerrado Treviño, A., Loureiro, J., Coutinho, P., & Sánchez Navarro, A. (2022). Development of a mucoadhesive vehicle based on lyophilized liposomes for drug delivery through the sublingual mucosa. Pharmaceutics, 14(7), 1497.
Bhattacharyya, A.; Chattopadhyay, R.; Mitra, S.; Crowe, S.E. Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev. 2014, 94, 329–354. [CrossRef]
Farzaei, M.H.; Abdollahi, M.; Rahimi, R. Role of dietary polyphenols in the management of peptic ulcer. World J. Gastroenterol. 2015, 21, 6499–6517. [CrossRef]
Rieder, F.; Biancani, P.; Harnett, K.; Yerian, L.; Falk, G.W. Inflammatory mediators in gastroesophageal reflux disease: Impact on esophageal motility, fibrosis, and carcinogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 298, G571–G581. [CrossRef]
Rao, C.V.; Vijayakumar, M. Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin, on experimental reflux oesophagitis in rats. Eur. J. Pharmacol. 2008, 589, 233–238. [CrossRef]
Gurlek, I.K.; Muderrisoglu, A.; Er, Z.C.; Arici, A.; Kupeli, M. Evaluation of effects of curcumin on acute esophagitis in the corrosive esophagitis model in rats. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2024, 397, 6677–6683. [CrossRef]
Macedo, A. S., Castro, P. M., Roque, L., Thomé, N. G., Reis, C. P., Pintado, M. E., & Fonte, P. (2020). Novel and revisited approaches in nanoparticle systems for buccal drug delivery. Journal of Controlled Release, 320, 125-141
MDPI review 2025 (sections on Marshmallow and Slippery Elm), Nutrients review, Pre-clinical/clinical data (PMC, PMC)
Bonaterra?G?et?al., Frontiers in Pharmacology, 2020; cited in MDPI GERD review (Reddit, PMC)
Saha, P. U. J. A., Verma, S. U. S. H. M. A., & Das, P. S. (2017). Sublingual drug delivery: an indication of potential alternative route. Int. J. Curr. Pharm. Res, 9(6), 5-7.
Macedo, A. S., Castro, P. M., Roque, L., Thomé, N. G., Reis, C. P., Pintado, M. E., & Fonte, P. (2020). Novel and revisited approaches in nanoparticle systems for buccal drug delivery. Journal of Controlled Release, 320, 125-141.
Jyothi B. et al. (2023) – IJPPR Review on Sublingual FilmsOverview of formulation variables (polymer types, plasticizers, pH modifiers) and evaluation metrics such as surface pH and folding endurance (pp.?379–380 review sections)
Muglikar D. R. et al., 2023Formulation and Evaluation of Fast Dissolving Oral Film Containing Extracts of Ocimum sanctum and Glycyrrhiza glabra to Treat Mouth Ulcer Journal: European Chemical Bulletin, Volume 12, Special Issue 10, Pages 2126–2130
Khan S. et al., 2022Title: Herbal Approaches to Acid Peptic Disorders: Role of Natural RemediesJournal: Asian Journal of Research in Pharmaceutical Sciences, Volume 12(1), Pages 28–32.
Alhamhoom Y. et al., 2024Title: Development of Sublingual Fast-Dissolving Loratadine Films Using HPMC and Citric AcidJournal: Polymers (MDPI), Volume 16, Issue 20, Article ID: 2919, Section 3.2.3, Pages 7–10.
Prasanth V.V. et al., Pharmacogn Rev. (2020), Deshmukh P.T. et al., J. Ayurveda Integr. Med. (2021)
Yadav P., Kumar R., Recent Patents on Drug Delivery & Formulation, 2021
Vaidya MM and Khutle NM, Gide PS. Oral fast dissolving drug delivery system: A modern approach for patient compliance. World Journal of Pharmaceutical Research.2013;2(3):558-577.
Gowri R, Narayanan N, Revathy S, Prabhavathy P, Preethi Mol G and Rekha G. Melt in mouth films- An effective alnernative drug delivery system. International Journal of Biological & Pharmaceutical Research. 2013;4(9): 645-650.
Satam MN, Bhuruk MD and Pawar YD. Fast dissolving oral thin film- A review. International Journal of Universal Pharmacy and Bio Sciences. 2013;2(4):27-39.
Kumar SV, Gavaskar B, Sharan G and Madhusudhan Rao Y. Overview on fast dissolving films. International Journal of Pharmacy and Pharmaceutical Sciences. 2010;3(2):29-33.
Nagar P, Chauhan Iti, Yasir M. Insights into Polymers: Film Formers in Mouth Dissolving Films. Drug invention today. 2013; 3(12): 280-289.
Bhura N, Sanghvi K, Patel U, Parmar B and Patel D. A review on fast dissolving film. International Journal of Pharmacy and Biological Sciences .2012; 1(3): 66-89.
Jurulu NS. Fast dissolving oral films: A review. International Journal of advances in Pharmacy, Biology and Chemistry. 2013; l2(1): 108-112.
Ghodake PP, Karande KM, Osmani RA, Bhosale RR, Harkare BR and Kale BB. Mouth dissolving films: An innovative vehicle oral drug delivery.International Journal of Pharmaceutical Sciences Review and Research. 2013; 2(10):41-47.
Bhupinder B and Jangra S. Formulation and evaluation of fast dissolving sublingual films of Rizatriptan Benzoate. International Journal Drug Devlopment&Reserach. 2012; 4(1):133-143.
Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharmaceut Sci. 1998;1(1):15-30.
Rathbone MJ, Hadgraft J. Absorption of drugs from the human oral cavity. Int J Pharm. 1991;74(1):9-24.
Patel VF, Liu F, Brown MB. Advances in oral transmucosal drug delivery. J Control Release. 2011;153(2):106–116.
Gandhi RB, Robinson JR. Oral cavity as a site for bioadhesive drug delivery. Adv Drug Deliv Rev. 1994;13(1-2):43–74.
Kurosaki Y, Takatori T, Nishimura H, Nakayama T, Kimura T. Regional variation in oral mucosal drug absorption: permeability and degree of keratinization in hamster oral cavity. Pharmaceutical research. 1991 Oct; 8:1297-301.
Aniket Thul
Corresponding author
S.N.D College of Pharmacy, Babhulgaon, Yeola India [423401]
10.5281/zenodo.17263993