Table 3.

Recent application of mucoadhesive dosage form for nutraceutical ingredients.

Sl. No	Bioactive Compound	Mucoadhesive Polymer	Mucoadhesive Formulation	Study Objective	Study Method	Research Findings	Reference
1	Zinc sulfate	Carbopol 940 + sodium alginate	Tablets	Zinc sulfate for the treatment of recurrent aphthous stomatitis (RAS)	Human clinical trial conducted with 46 participants having RAS	Conducted clinical trial with mouth ulcer patients, and authors found that the zinc tablets can reduce the pain, diameter of ulcer wounds and its inflammation, and accelerates the recovery time of ulcer.	[37]
2	Chitosan	Polyurethane + chitosan	Films	Chitosan mucoadhesive film for the treatment of RAS	Human clinical trial. 72 participants were recruited for the study and conducted data analysis with 66 subjects	Chitosan film promoted the healing of RAS, and the pain score was significantly reduced from day 4 to day 6. Chitosan films shielded the ulcer from external stimuli and thereby reduced the related pain from the ulcer region.	[38]
3	α-mangostin	Chitosan + alginate	Hydrogel films	α-mangostin hydrogel film for the treatment of RAS	In vitro release and mucoadhesive study in mouse mucosa	Chitosan +alginate +α-mangostin hydrogel films were adhesive toward the mouse mucosa for 46.7 min, and showing burst release characteristics, which is necessary for the treatment of RAS.	[39]
4.	Ginger extract	Tragacanth gum	Films	Ginger extract for the treatment of RAS	Clinical study in 15 patients	The mucoadhesive ginger formulation can relieve the pain of RAS patients; however, there is no statistical difference in the ulcer diameter, healing time with placebo.	[40]
5.	Curcumin	Hydroxypropyl methylcellulose + glycerin	Patches of 2 × 3 cm containing 2% curcumin	Curcumin for the treatment of oral submucous fibrosis (OMSF). OSMF is a chronic inflammatory, and immune-mediated disease occurs commonly by chewing arecanuts	Forty patients with OMSF in two groups. One group of patients was administered with curcumin gel and another group was administered with curcumin mucoadhesive patches	All patients were relieved from a burning sensation in the oral cavity, and the patients can open the mouth by 5.9 ± 2.00 mm. The curcumin patches were easy to apply and provided a non-invasive mode of treatment for OSMF.	[41]
6.	Curcumin	Zein + beta-cyclodextrin	Curcumin loaded nanoparticles	Develop Mucoadhesive zein NPs for curcumin buccal delivery	Ex vivo study. Mucoadhesive properties were conducted with buccal mucosa from freshly killed pigs	Curcumin permeation study revealed the highest curcumin permeation for zein cyclodextrin mucoadhesive formulation than the curcumin nanoparticles.	[42]
7	Curcumin	Gellan gum + Pectin	Films	The efficiency of gellan gum and pectin mucoadhesive formulation for delivering curcumin	In vitro release kinetics and disintegration	The mucoadhesive film was not disintegrated after 24 h exposed to simulated saliva. That means the film can remain in the target site for a prolonged time and release the therapeutic compounds. In vitro release study showed that there was an initial burst release till the first 10 min of exposure and then the release rate lowered up to 60 min of the test. Fast swelling of the film and rapid liquid uptake attributed to initial burst release behavior.	[43]
8	Curcumin	Poloxamer 407 + Carbopol 974P	Films	Develop nanostructured curcumin incorporated in films to target oral squamous cell carcinoma	In vitro release study, and ex vivo mucosal permeation in the porcine oral mucosa	A complete release of curcumin after 8 h exposure in the in vitro simulated condition, which makes it a suitable formulation for a buccal application.	[44]
9	Curcumin	Poly (L-lactic acid)	Patch	Develop mucoadhesive patch containing curcumin nanofibers using electrospinning techniques	In vitro release study and ex vivo adhesive properties in porcine buccal mucosa	Curcumin patch showed the least adhesion force of 0.14 ± 0.01 N, attributed to the non-mucoadhesive characteristics of polymer PLLA.	[45]
10	Resveratrol	Chitosan + Zein	Nanoparticles	Effectiveness of chitosan-coated zein nanoparticles for the oral delivery of resveratrol	In vitro mucoadhesion study in mucin solutions	Particle diameter was increasing with increasing mucin concentration as more mucin adsorbs on the nanoparticle surface. Thus, chitosan-coated nanoparticles were showing a higher increment in size than the uncoated particles.	[46]
11	Resveratrol	Hydroxypropyl cellulose + ethyl cellulose	Films	Optimize the polymer concentration on the mucoadhesive strength, swelling, and in vitro release	In vitro release study and ex vivo permeation study with goat buccal mucosa	Ex vivo permeation study revealed that there was a restriction in resveratrol permeation due to the low wetting and hydration of polymer matrix. In addition, the low aqueous solubility of resveratrol limited the release and penetration characteristics.	[47]
12	Peanut skin extract	Gelatin + hydroxypropyl methylcellulose	Films	Develop polyphenol enriched films using the casting technique	In vitro release technique	Mucoadhesive films followed the initial burst release of phenolic content about 1.2 mg gallic acid equivalent, attributed to the hydrophilic polymer, hydroxypropyl methylcellulose.	[48]
13	Pomegranate fruit extract	Carboxymethyl cellulose	Films	Produce multilayered oral films using printing techniques incorporating phenols	In vitro release technique	The release of polyphenols from the films showed a Fickian diffusion pattern, and the phenolic compounds were stable for 196 days at room temperature.	[49]
14	Vitamin B-12	Chitosan + Polyvinyl alcohol	Films	Develop vitamin B-12 mucoadhesive hydrogel films	In vivo pharmacokinetic study with rabbits	Compared the release of vitamin B12 from the buccal films and commercial Neuroton I.M. injection. The area under the curve (AUC0–8h) showed a 1.5-fold increase in bioavailability from the buccal film compared with the I.M. injection.	[50]
15	Vitamin B12	Hydroxypropyl methyl cellulose + Carbopol + chitosan	Tablets	Develop buccal tablets of vitamin B12 and improve the oral bioavailability	In vivo pharmacokinetic study with rabbits	Rabbits injected with vitamin B12 (intramuscular) showed rapid release till 15 min at a maximum concentration of 109.29 ± 9.39 pg/mL and gradually decreased to 43.23 ± 2.034 pg/mL at 30 min. Rabbits administered with buccal tablets were released vitamin B12 in a sustained release manner and showed a 2.7-fold increase in bioavailability compared to the I.M. injection.	[35]
16	Vitamin K	Labrasol + Transcutol	Self-nano emulsifying lyophilized tablets	Improve the oral bioavailability of vitamin K	Human clinical trial. A group of volunteers administered buccal tablets and another group with intramuscular injection	Pharmacokinetic study in human volunteers revealed the buccal tablets enhanced vitamin K absorption and relative bioavailability. Interestingly, there was no significant difference in the vitamin K in systemic circulation for the two groups of volunteers.	[51]
17	B-complex vitamins: thiamine hydrochloride (THCl) and nicotinic acid (NA)	Propylene glycol	Films	Develop vitamin B-complex buccal films by inkjet printing technique	In vitro technique	Both vitamins are released within 10 minutes from the buccal film. For increasing vitamin content, there was an increase in permeation across the cellulosic membrane.	[52]