Progressive Education Society’s Modern College of Pharmacy, Nigdi, Pune, Maharashtra, India- 411044
The aim of this study was to develop and evaluate oral patches containing herbal extracts with antiulcer activity. Four herbal extracts (guava, lavender, thyme and chamomile) were selected based on their traditional use in gastric disorders. The results showed that the buccal patches showed significant anti-ulcer activity, with guava and lavender showing the highest activity. The patch showed faster drug release and better immune response compared to the control group. This study demonstrates the potential of herbs as a novel and effective treatment for oral ulcer.
Ulcer:
Mouth ulcers, medically known as aphthous ulcers, are diseases of the mucous membranes of the oral cavity. Although they are common and often associated with many conditions, most conditions do not indicate a serious problem. However, persistent, and non-healing disease may be a sign of oral disease. These lesions may appear singly or in groups called "ulcers." Once they form, inflammation and/or secondary infection may cause the sore to become permanent.
Figure no. 1 Ulcer
Oral disease is a disease caused by two main sources: local injury and aphthous stomatitis. Local injuries are common, such as abrasive friction from broken teeth or braces, or accidentally biting the lip. In contrast, aphthous stomatitis is a mysterious disease caused by the outflow from the mouth, which remains unclear. These aphthous ulcers, regardless of their origin, herald a period of discomfort and pain for the patient. During recovery, people are often forced to change their diet and avoid acidic, sweet, salty or spicy foods and drinks. This austerity diet is due to a pragmatic need to reduce the discomfort caused by such products in the sensitive area of ??the mouth. Therefore, the interaction of etiology, symptomatology and dietary changes leads to different properties of masks.
Route of administration:
Oral local administration offers an attractive alternative, especially in overcoming the disadvantages associated with the oral route of administration. Oral local administration avoids problems such as first-pass metabolism and degradation of the drug under the weight of the intestinal environment. Oral local administration can also be used in patients who cannot undergo oral administration by this method. Many mucoadhesive buccal membranes have been developed to deliver drugs locally to treat oral diseases such as oral candidiasis. Due to the variety of manufacturing processes, the release can be in the void or the void. These materials are usually prepared by pouring a solution of polymer, chemicals, and other excipients (such as plasticizers) onto the surface and allowing it to dry. The size of the patch can be 10-15 cm2, but is usually 1-3 cm2 and is oval shaped to fit perfectly in the middle of the buccal mucosa. (15) Required oral local administration provides a safe way of drug administration because, in case of toxicity, drug absorption can be stopped quickly by removing the essential information. Therefore, recommended oral administration forms include adhesive tablets, adhesive gels, and adhesive patches. However, regarding comfort and convenience, buccal patches are better than adhesive tablets. Various research groups have investigated and reported the oral delivery of various therapeutic drugs using drug matrices, patches, and hydrogels. Technically, a good buccal adhesive system should maintain its position in the mouth for several hours, allowing a controlled unidirectional release of the drug into the mucosa. (2) The buccal route is a method of administration, bypassing the first batch of drugs in the liver and entering the system directly from the blood vessels in the body, providing high bioavailability. (3) Although it is known that the sublingual mucosa is more permeable than the buccal mucosa, the preferred method for transmucosal drug delivery is the buccal mucosa. This is because the buccal mucosa consists of smooth muscle and immobile mucosa, making it an ideal storage site. Therefore, the buccal mucosa is suitable for the sustained delivery of impermeable drugs and peptide drugs.
Structure and composition of oral materials:
Oral materials can be:
1. Matrix type: Buccal patches have a matrix structure that contains the drug, binders, and additives are mixed.
2. Reservoir: A space for medication and additives to be separated from the adhesive in the buccal patch system. Use the impermeable back to control the direction of medication delivery; (4)
Advantages:
The buccal method has many advantages, such as good penetration, non-keratinized mucosa, dense capillary network, large absorption area, no enzyme activity, patient acceptance, no first-pass metabolism, better control of blood plasma, small bioavailability changes and minimal changes. (2)
Guava leaves
This study includes the use of herbal powdered guava leaves in the treatment of mouth ulcers in buccal patches. It is commonly known as guava, Peruvian guava, Ambrud. Its root is Psidium guajava from the Myrtaceae family. The chemical composition includes flavonoids, triterpenoids, steroids, carbohydrates, fats, lipids, glycosides, alkaloids, tannins and saponins. It is used as anti-oxidant, anti-inflammatory, anti-bacterial and anti-cancer. (6)
The present study deals with use of herbal guava leaves with other active ingredient in treatment of mouth ulcer in buccal patches.
Lavender
Lavender is a Mediterranean plant belonging to the Lamiaceae family. Lavender flowers (Lavandula flores) contain active substances (3%), anthocyanins, sugars, phytosterols, minerals and tannins and are frequently used in herbal medicine. The definition and analysis of the composition of lavender essential oil varies according to genotype, cultivation area, climate, production, and morphological characteristics. There are about 300 chemical compounds in essential oils. Linalool, terpinen-4-ol, linalyl acetate, ocimene, lavenderol acetate and eucalyptus are the most important components. Lavender oil has antibacterial and antioxidant properties. Lavender extract helps prevent dementia and can slow the growth of cancer cells, while lavender oil is used to treat skin problems. (15)
Thyme
The English word "thyme" covers the most used genus and species, Thymus vulgaris L. (common thyme, garden thyme). T. vulgaris is really the most important species from an aromatic and herbal point of view and is widely used as an aromatic and herbal medicine. That is, T. vulgaris is the parent species of this section, and unless another botanical name is specified, "thyme" here refers to T. vulgaris. However, other species of Thymus should also be included here as they are used for similar purposes or as alternatives to T. vulgaris, especially T. zygis L. (Spanish thyme), T. serpyllum L. (Wild thyme, Thymus vulgaris), thiab T. pulegioides L. (Great thyme los yog loj prayer thyme). Commercial products from these four species include essential oils, oleoresins, fresh and dried herbs, and landscape plants. The antispasmodic activity of thyme is due to the antioxidant thyme. (8)
Chamomile
One of the most common herbs used for medicinal purposes is chamomile, a tea and herbal extract made from the dried flowers of the Matricaria species. Chamomile is one of the oldest, most widely used, and best-documented medicinal herbs in the world and has been recommended for many medicinal uses. Chamomile is native to the Old World and is a member of the daisy family (Asteraceae or Asteraceae). The hollow, bright golden panicles are filled with disc- or tube-shaped flowers and are surrounded by about fifteen white, tongue-shaped flowers. Chamomile is represented by two widely known species; German chamomile (Matricaria chamomilla) and Roman chamomile (Chamaemelum nobile). In this review, we will discuss the uses and benefits of chamomile, reviewing its history of use and recent research and reviews on its ability to treat a variety of ailments. (10)
Table no. 1 Brief information about the herbal component
|
Sr. no |
Constituent |
Synonyms |
Biological Source |
Family |
Active Constituents |
Therapeutic Uses |
|
1. |
Guava Leaves |
Peru, Amaroot |
Psidium guajava L. |
Myrtaceae |
quercetin, kaempferol, catechins, phenolic acids, gallic acid, ellagic acid, tannins, triterpenes, sesquiterpenes, cineole, alpha-pinene, limonene, vitamin C, vitamins A, vitamin B, vitamin E, beta-carotene, lycopene, and lutein.
|
Antioxidant, anti-inflammatory, antimicrobial, antidiabetic, cardioprotective, anticancer |
|
2. |
Lavender |
Lavandula officinalis, lavandula vera |
Lavandula angustifolia |
Lamiaceae |
linalool, linalyl acetate, 1,8-cineole, camphor, terpinen-4-ol, quercetin, apigenin, ursolic acid and oleanolic acid |
Antioxidant, anti-inflammatory and antimicrobial activities |
|
3. |
Thyme |
Thymus serpyllum, thymus zygis |
Thymus vulgaris |
Lamiaceae |
Thymol, Carvacrol, Rosmarinic acid, Flavonoids and Tannins |
Antimicrobial, antioxidant, anti-inflammatory, antispasmodic, antitussive and expectorant |
|
4. |
Chamomile |
Karpurapuspa, Baboona, German chamomile
|
Matricaria chamomilla |
Asteraceae |
Sesquiterpenes, monoterpenes, Apigenin, luteolin, quercetin, Herniarin, umbelliferone, caffeic acid derivatives and phenolic acids |
Anti-inflammatory, Antioxidant, Relaxant, wound-healing, and Sedative |
Formulation:
Design of buccal mucoadhesive patch: The different ingredients of buccal mucoadhesive patch are as follows:
1. Chemical (Drug)
2. Polymer (preparation of mucoadhesive polymer, release rate control polymer and backing polymer).
3.Penetration enhancer.
1. Drug: The basic properties of the drug that affect its distribution in the region and the oral cavity include molecular weight, chemical activity and melting point. For the production of oral mucoadhesive drugs, appropriate drugs must be selected based on pharmacokinetics.
The main features of buccal mucosal drug candidates are:
a) The drug must be less than one routine time.
b) The taste of drug should not be bad and irritancy should not appear.
c) Drugs should not affect the natural microbial flora or the oral cavity.
2. Mucoadhesive polymers: Since the contact between the formulation and the buccal mucosa is an important factor in effective buccal delivery, the use of mucoadhesive polymers in the formulation of the buccal drug delivery machine is now of greater importance. The adhesion of materials to the mucosa can be considered as the result of the following steps: hydration of the polymer, wetting of the mucosa, diffusion into the mucosa, and chemical binding to glycoproteins. Hydrated polymers wet the slime when interatomic and intermolecular forces occur at the interface. The formulation of the product is determined by the liquid-solid contact stage and therefore good wetting and weak interaction between the two materials must be taken into account. The strength is determined by the secondary chemical properties created by the chain/mucin interlocking, which is affected by the flexibility and fluidity of the polymer. Therefore, an ideal bioadhesive polymer should have satisfactory strength and chain flexibility, functional groups that facilitate its diffusion and dispersion in mucus, and should form secondary chemical bonds (e.g., ionic and hydrogen bonds).
The most suitable materials for bioadhesion are hydrogel-forming polymers, which are cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, methylethylcellulose, and hydroxyethylcellulose. Natural gums such as karaya and polymers such as starch, sodium alginate, and pectin such as polyvinylpyrrolidone can also be used. The high molecular weight of polyethylene oxide (PEO) and polyethylene glycol (PEG) exhibit good mucoadhesive properties due to their linear flexible molecular structures and their ability to form physical bonds that entangle mucus. Polymer mucoadhesive patches that control the release of drugs from the oral cavity: Saliva or water-insoluble polymers work well as a matrix system or polymers where the rate of drug release can be controlled as required. Examples of this group include ethyl cellulose and butyl rubber. Water soluble polymers can be used to control the release rate, where the rate of polymer dissolution will determine the release. Polymers used to prepare the film for recovery: Polymers that can be extruded into thin, water resistant, irregular and negative film can be used to prepare the film for patching. They should have flexibility and high tensile strength and low water permeability. They should remain stable and retain their original properties during long term storage. Cellulose acetate at a concentration of 2.4% w/v in acetone containing 10% plasticizer (PEG 4000 or glycerin) based on the total weight of the polymer produces films suitable for support applications in dry weather. Similarly, ethylcellulose can be cast into films with a 2-4% w/v solution in a 1:4 alcohol:toluene mixture and a suitable plastic material. The main function of the back membrane is to provide a single drug flow to the gastric mucosa. It prevents the drug from coming into contact with the saliva by preventing the drug from dissolving in the saliva and thus being swallowed. The material used for the back membrane should be inert and impermeable to chemicals and penetration enhancers. The thickness of the back film should be thin and should be around 75-100 microns. The most commonly used material is polyester laminated paper with polyethylene. Other examples include cellophane-325, multiform paper, and polycellophane.
Plasticizers: These materials are used to increase softness and flexibility in polymer materials or polymer blends. Examples of commonly used plastics include glycerin, propylene glycol, PEG 200, PEG 400, castor oil, etc. Plasticizers help release the drug from the polymer matrix and act as penetration enhancers. When used in the right proportions with polymers, these materials reduce molecular rigidity and provide flexibility.
3. Penetration enhancer: Drugs that facilitate the passage of drugs through the oral epithelium are called penetration enhancers, penetration enhancers or absorption enhancers. Drugs used as disinfectants must be safe and non-toxic, pharmacologically and chemically inert, non-irritating and non-allergenic. In addition, the removal of chemicals, surfactants, anions (such as sodium laurate and sodium lauryl sulfate), cations (such as cetylpyridinium chloride) and non-ions (such as poloxamer, brij, span, myrj and tween) must be restored from the tissues integrity and barrier power. Bile salts are believed to create a flow by displacing water from the membrane and reversing micellization in the membrane. Fatty acids such as oleic acid and carboxylic acid increase phospholipids in the intercellular lipid space, and cyclodextrins act as integrated membrane drug penetrators. Cationic polymers such as chitosan and poly-L-arginine are known to work by neutralizing mucosal surfaces and opening tight junctions. Due to the similarity between the oral mucosa and the skin, drug developments and worms that enhance transdermal delivery in the oral mucosa are also being used. Various amounts of ethanol (5% and 30%), propylene glycol, n-methylpyrrolidone, and dimethyl sulfoxide have been used as introductions to oral literature. Protease inhibitors such as aprotinin, betastatin, puromycin, and bile salts can also be used; these are peptides that have been tested and found to reactivate oral enzymes. (4)
Experimental work of buccal patches showing anti-ulcer activity
Aim: To investigate the potential antiulcer activity of buccal patches containing extracts of guava leaves, thyme, lavender and chamomile for the management of oral ulcers.
OBJECTIVE:
Isolation and characterization of bioactive substances with preservative and improving properties of guava leaves, thyme, lavender and chamomile. composed of bioactive compounds.
Materials and Method for crude drug:
Guava leaves: Freshly grown Guava was collected from a local farm. Wash the fresh leaves in distilled water and dry them in shade. The collected plants were identified by the Department of Pharmacognosy, Modern College of Pharmacy. (6)
Lavender plant: Lavandula angustifolia was procured from a supplier. The plant (L. angustifolia) was successfully grounded using an electric machine. The powder was soaked in 70% ethanol for three days with continuous stirring to extract all the compounds in angustifolia into a heavy solution (ethanol). Filter the solution through Whatman filter paper and discard the filter solution. This process was repeated three times to ensure that all polar compounds were removed. The filtrate was evaporated almost to dryness using a field evaporator to obtain the raw material used to evaluate the biological activity of lavender. (11)
Thyme: Thyme was provided as aqueous and alcoholic extract. Thyme is found in liquid and alcoholic beverages. Prepare a solution of 20 mg/ml, the maximum soluble concentration, in water and 70% ethanol. The solutions were sterile filtered and stored at 4°C. (5)
Chamomile:
The chamomile powder was soaked in methanol [5% (w/v)] on a shaker for 4 h, filtered, and evaporated in a Petri dish at room temperature. The dried product was recovered and stored in tubes at -20°C until use. A 100 mg/mL solution was prepared by dissolving the methanol solution in dimethyl sulfoxide (DMSO). (12)
Excipients:
HPMC (Hydroxypropyl Methylcellulose): A mucoadhesive polymer used as a base for the patch.
SLS (Sodium Lauryl Sulphate): An emulsifier and solubilizing agent.
Glycerine: Used as a plasticizer to impart flexibility to the patch.
Distilled water: As a solvent and to adjust the viscosity of the formulation.
Citric acid: Used as a pH adjuster.
Guava leaves
Thyme extract
Lavender extract
Chamomile extract
Figure no. 2 Herbal components
Preparation of mucoadhesive patches:
HPMC gel (3% w/v) was prepared as described by Kumar and Himmelstein (1995): one weight of polymer (HPMC) was slowly added to 1/3 of the desired volume of distilled water (90 °C) with a constant stirring. Then, add appropriate amounts of guava leaf powder, thyme, lavender, and chamomile extract. The next step is to add additional chemicals (citric acid, SLS and glycerol) and make up the final volume by adding cold water (5 °C). Pour the gel mixture into the Mold and let it dry. The dried films were cut into patches of 10 mm diameter and packed in aluminium foil and stored in glass containers maintained at room temperature, 58% relative humidity. (7)
Results and discussion of antiulcer activity for patches:
Measure the thickness of the patch using a thickness gauge at six different points on the patch. The thickness of the patch affects the working time of the preparation. The mean patch thickness was found to be 0.12,0.13,0.09(mm) of the patch F1, F2 and F5 respectively.
Figure no. 3 Measuring patch thickness
Table no. 2 Observed values
|
|
Formulations |
Patch Thickness |
Patch Texture |
Colour |
|
1 |
F1 |
0.12 mm. |
smooth |
Yellow |
|
2 |
F2 |
0.13 mm. |
smooth |
Yellow |
|
3 |
F3 |
0.13 mm. |
smooth |
Yellow |
|
4 |
F4 |
0.09 mm. |
smooth |
Yellow |
|
5 |
F5 |
0.10 mm. |
smooth |
Yellow |
|
6 |
F6 |
0.11 mm. |
smooth |
Yellow |
Patch Weight was conducted to evaluate the uniformity of dosage. The mean patch weight was found to be 0.0159,0.0131,0.0162(mg) of the patch F1, F2 and F3 respectively.
Figure no. 4 Weighing the patch
Table no. 3 Observed values
|
Sr. no |
Formulations |
Patch weight |
|
1 |
F1 |
0.0159 mg. |
|
2 |
F2 |
0.0131 mg. |
|
3 |
F3 |
0.0162 mg. |
|
4 |
F4 |
0.0181 mg. |
|
5 |
F5 |
0.0126 mg. |
|
6 |
F6 |
0.0107 mg. |
Moisture content was conducted to evaluate the moisture present in
the formulation also the stability of formulation. The percentage
moisture content was found to be 0.0152, 0.0125 and 0.0155
respectively.
Figure no. 5 Pre-weight of moisture content
Table no. 4 Pre-weight of moisture content:
|
Sr No. |
Formulation |
Pre-weight of patch (grams) |
|
1 |
F1 |
0.0159 |
|
2 |
F2 |
0.0131 |
|
3 |
F3 |
0.0162 |
|
4 |
F4 |
0.0181 |
|
5 |
F5 |
0.0126 |
|
6 |
F6 |
0.0107 |
Table no. 5 Post-weight of moisture content:
|
Sr No. |
Formulation |
Post-weight of patch (grams) |
|
1 |
F1 |
0.0152 |
|
2 |
F2 |
0.0125 |
|
3 |
F3 |
0.0155 |
|
4 |
F4 |
0.0178 |
|
5 |
F5 |
0.0119 |
|
6 |
F6 |
0.0100 |
Folding is also done to measure the strength of all aspects of the design; for example, to study the behaviour of the field in response to the stress applied by the fold.
Figure no. 7 Checking the folding endurance
Table no. 6 Observed values
|
Sr No. |
Formulation |
Folding Endurance |
|
1 |
F1 |
48 |
|
2 |
F2 |
46 |
|
3 |
F3 |
49 |
|
4 |
F4 |
45 |
|
5 |
F5 |
48 |
|
6 |
F6 |
49 |
The surface PH of the patches was conducted to evaluate the solubility, stability and biological Tolerability. The surface PH of the patches was found to be 5.7, 4.5, and 4.2 of F1, F2 and F3 respectively.It was found to be a bit acidic.
Figure no. 8 Measuring the surface pH of patch
Table no. 7 Observed values
|
Sr No |
Formulation |
Surface pH |
|
1 |
F1 |
5.1 |
|
2 |
F2 |
4.5 |
|
3 |
F3 |
4.2 |
|
4 |
F4 |
4.4 |
|
5 |
F5 |
3.9 |
|
6 |
F6 |
5.7 |
Anti-Microbial Efficacy was conducted to evaluate the anti-microbial efficiency of the formulated patches. The formulated patches are used to treat caries which are caused by various bacteria like S. Aureus, S. Mutans etc. Thus, the anti-microbial efficacy of formulation is necessary to be evaluated
Figure no. 9
Formulation no. 1
Figure no. 10
Formulation no. 2
Figure no. 11
Formulation no. 3
Figure no. 12
Formulation no. 4
Figure no. 13
Formulation no. 5
Figure no.14
Formulation no.6
Table no. 8 Observation of Diameter of Inhibition (DOI):
|
Formulation |
1 (cm) |
2 (cm) |
3 (cm) |
4 (cm) |
Mean diameter (cm) |
|
F1 |
3.4 |
3.5 |
3 |
3 |
3.22 |
|
F2 |
3.4 |
3 |
2.6 |
3.1 |
3.0 |
|
F3 |
3.3 |
3.7 |
3.1 |
3.4 |
3.3 |
|
F4 |
3.2 |
2.8 |
2 |
2.9 |
2.7 |
|
F5 |
2.5 |
2.4 |
2.6 |
3.4 |
2.7 |
|
F6 |
3.1 |
4 |
3.9 |
3.8 |
3.7 |
Table no. 9 Zone of Inhibition:
|
Formulation |
Zone of Inhibition. (cm2 ) |
|
F1 |
6.8 |
|
F2 |
6.1 |
|
F3 |
7.8 |
|
F4 |
4.6 |
|
F5 |
4.6 |
|
F6 |
9.7 |
CONCLUSION:
From the above observed information, an herbal formula for the remedy of ulcers turned into advanced formula in form of buccal patches. The system become primarily based on a aggregate of traditional medicinal herbs acknowledged for their anti-ulcer activity, together with guava leaves, thyme, chamomile and lavender. The buccal patch transport system became chosen for its capability to offer localized and sustained launch of active components at once to the site of ulceration, thereby improving healing efficacy. The prepared buccal patches had been subjected to numerous opinions, along with patch thickness, weight variation, moisture content, folding endurance, surface pH and in-vitro studies. The natural buccal patches confirmed promising anti-ulcer results, as evidenced with the aid of reduced lesions and more suitable mucosal healing. Moreover, the usage of natural components with well-documented healing houses gives a delivered advantage of fewer facet results in comparison to artificial capsules. This study concludes that the herbal buccal patch components holds incredible capability as an powerful, non-invasive remedy alternative for ulcers.
REFERENCE
Shivraj Mane*, Anushka Kamble, Lochan Khadke, Shweta Mehtre, Herbal Formulation and Evaluation of Buccal Patches Showing Anti-Ulcer Activity, Int. J. Sci. R. Tech., 2025, 2 (3), 495-504. https://doi.org/10.5281/10.5281/zenodo.15090016
10.5281/10.5281/zenodo.15090016
