Formulation and Evaluation of Herbal Lozenges for the Effective Management of Mouth Ulcers

An open sore on the skin or mucous membrane, an ulcer is defined by the sloughing off of inflammatory dead tissue [1]. A superficial loss of tissue characterizes ulcers, which are sores on the skin's surface or a mucous membrane. Whilst they can occur practically anywhere, ulcers are most frequently found on the skin of the lower limbs and in the gastrointestinal system.

Mouth ulcer:

Aphous stomatitis, often known as mouth ulcer, is an inflammatory disease that affects the oral mucosa and is marked by recurrent oral and throat ulcers.9. About 20% of the general population is considered to be affected by this prevalent disease; in children, the estimated prevalence is 9%. (2).

Types of mouth ulcer:

1. Minor aphthous ulcer:

About 80% of people with RAS have minor aphthous ulcers, which are the most prevalent kind of RAS. They occur every one to four months. Small (typically less than 5 mm in diameter), round or oval, and presenting as one to six ulcers at a time, these lesions are. A grey-white pseudo membrane covers the lesions and an erythematous halo encircles them. In [3] Mostly occurring in non-keratinized mucosa, such as the floor of the mouth, buccal, and labial mucosa (see Image: Aphthous Ulcer), minor RAS cures on its own in two weeks without leaving any scars. In [3] Phthous lesions may appear before oral pain.

Fig. 1: Minor ulcer

2. Major aphthous ulcer:

Slightly more than 10% of RAS patients would develop major aphthous ulcers, sometimes referred to as periadenitis mucosa necrotica recurrent. More than 10 mm in size, the ulcers typically leave scars and persist for 5 to 10 weeks. Oropharynx and other oral regions could be impacted [3].The majority of RAS in AIDS patients are major aphthous ulcers, and there is a stronger correlation between these lesions and hematological and gastrointestinal issues.

Fig. 2: Major ulcer

3. Herpetiform ulcer:

The least prevalent kind of RAS, herpetiform ulceration, affects 1% to 10% of patients. [3] There is no relationship to herpes viruses; rather, the name comes from the similarity to primary herpetic stomatitis. Older females are more likely to get herpetiform ulcers. [5] The lesions look like countless, tiny, painful ulcers. Up to 100 ulcers may appear at once, each with a diameter of 2 to 3 mm and a duration of one to two weeks. [3] The tongue's tip and lateral edges, as well as the floor of the mouth, are the most common locations. They could show up on mucosa that is keratinized or not. Occasionally, the little ulcers may merge to form a larger, uneven ulcer that leaves scars behind. [3]

Factors contributing to mouth ulcer:

1. including biting the inner layer of the cheek
2. food sensitivities,
3. brushing your teeth too firmly,
4. hormone fluctuations,
5. vitamin shortages,
6. bacterial infections, and illnesses, can result in mouth ulcers.

Mouth ulcers can be treated by using topial lozenges:

Lozenges are solid preparation meant to dissolve or disintegrate gradually in term they offend contain one or more medication in flavoured, sweetened foundation. They can be made via compression of sugar-based tablet.

Pathophysiology:

Cell-mediated immunity in the pathogenesis of recurrent aphthous stomatitis Lymphocytic cells infiltrate the oral epithelium and edema develops as a result of inflammatory stimuli. Keratinocyte vacuolization and localized vasculitis cause a papular swelling. The papule ulcerates and is infiltrated by neutrophils, lymphocytes and plasma cells, followed by healing and regeneration of the epithelium.

Treatment:

Symptomatic therapy is the most popular approach of treating mouth ulcers. Treatment for the illness is also recommended if the reason is identified. Relieving symptoms may also be aided by good oral hygiene. Aside from avoiding spicy or hot food, topical antihistamines, antacids, corticosteroids, and other treatments meant to soothe irritated ulcers may als o be helpful. Oral analgesics such as ibuprofen or paracetamol, as well as l ocal anaesthetics like benzocaine, lozenges, paints, or mouth rinses, may al so be helpful. The first line of treatment for aphthous stomatitis is topical medication rather than systemic medication. Topical corticosteroids are the most widely used treatment for aphthous stomatitis. Systemic treatment is often reserved for severe disease because several of these drugs have the potential to cause major negative effects. It’s also essential to practise goo d oral hygiene to avoid subsequent ulcer infection. Extensive study has dem onstrated the effectiveness of amlexanox as a topical treatment; however conclusive findings indicate that vitamin B12 supplementation and avoiding toothpaste containing sodium lauryl sulphate may help prevent a recur rence (9).

Mechanism of ulcer healing:

Fig no 3: Mechanism of ulcer treatment

Organic techniques

Dietary supplements and lifestyle modifications can be used to cure or pre vent canker sores.Despite the lack of scientific evidence, many have claime d to feel better after using them

Vitamins B: vitamins include vitamin B1, vitamin B2, and the B-complex. Take a prescription for a B complex on a regular basis.One kind of probiotic bacteria is Lactobacillus acidophilus (chew four Lactobacillus tablets three e times a day to relieve pain).People who have recurrent canker sores have been reported to benefit from Lactobacillus bulgaricus and Lactobacillus a acidophilus.

Chronic ulcer treatment:

Topical anesthesia

Topical anaesthetics frequently offer effective pain management (35). Benzocaine lozenges, 2% gel or spray, polidocanol paste, and 1% cream (b ased on a randomised placebo-controlled research; EL2A [36]) are among the available options. Tetracaine (0.5% and polidocanol (0.1%), combined in a pump spray. There’s also a mouthwash that contains cetylpyridinium chloride and benzocaine. Antiseptics and analgesics A mouthwash with 0.15% triclosan in ethanol and zinc sulphate decreased the amount of new aphthous ulcers in 43% of instances, the degree of pain in 45% of cases, and the length of the ulcer- free interval. After 2-4 hours, diclofenac 3% in a 2.5% hyaluronic acid gel reduced pain better than lidocaine 3% gel (15).

Tetracycline topical therapy:

To prevent issues with stabilisation, the patient can mix 250 mg of tetracyc line hydrochloride powder with 10 mL of tap water right before using it.

The pH level is acidic, which might produce brief burning of the mucosa, u sually followed by improvement in the clinical condition. It is also possible to produce a stable mixture by neutralising the tetracycli ne hydrochloride and producing a basic product. (16).

Types of Lozenges on the basis of composition:

1. Chewable lozenges:

Due to their gummy texture, these lozenges are chewed rather than dissolving in the mouth.Composed mostly of gelatin, glycerin, and water, which are combined and heated to form, they are composed of several kinds of gum, such as carrageenan, xanthan gum, starch, pectin, and algin. To mask the harsh flavor of glycerin, they include a high concentration of flavoring ingredient. [11]

Fig 4: Chewable lozenges

2. Hard lozenges:

Also referred to as solid sugar syrup, hard lozenges are a non-crystalline, amorphous solid combination of sugar and carbohydrates. One benefit of them is that they prevent the medicine from going through first pass metabolism, which causes it to dissolve in the stomach or buccal cavity after ingestion. They disintegrate or dissolve in around 10 minutes and have a moisture content of between 0.5 and 1.5%. Hard lozenges have the drawback of requiring a high temperature during formulation. It is mostly used to treat mouth or throat infections, as well as its demulcent and relaxing effects. [12]

Fig 5: hard lozenges

3. Soft Lozenges:

Due to their nature, soft lozenges are often utilized and may be administered to patients of all ages, including pediatric and elderly patients. They may be based on an acacia, PEG, or silica formulation and release the medication gradually over a certain amount of time. In this formulation, silica functions as a suspending agent to keep material from settling at the bottom when the material cools. They may be made by either putting the hot, melted material into a mold and then cooling it to form the shape of sachets, or by simply cutting the rolls by hand. [2]

Fig 6: soft lozenges

Table no 1: Classification of Lozenges

Advantages-

1. Lozenges have a definite size and shape so can be easily given to both geriatric and pediatric population. Most attractive for the children due to their various shape such as toys, animals, heart etc.
2. Sugar free lozenges can also be safely used for diabetic patient.
3. Bitter drug or drug having unpleasant smell or odour can be given with taste and odour masking agent.
4. Easily prepared so have time consuming and require minimum equipment.
5. By-pass first pass metabolism, reduce gastric irritation and increase bio- availability.
6. Do not require water for administration and have non-evasiveness.
7. Can be given for patient having difficulty in swallowing.

Disadvantages-

1. The most major disadvantage includes its resemblance to sweet sugar candies fantasized by children, hence should be kept out of the reach of children.
2. High temperature required for the preparation of hard candy lozenges.
3. Hard lozenges become grainy

Formulation of lozenges:

Table No. 2: Formulation of lozenges

Method of Preparation:

• For making lozenges, weigh a sucrose. Add 1ml of water and heat up to 110- 120? to make sugar syrup.
• Add corn syrup
• Add 0.6ml of clove oil with continuous stirring and turn off the gas.
• Allow it to get temperature below 95? and add coloring and flavoring agent,
• Pour into mold and keep aside for 1hour at room temperature to set lozenges
• Demold the lozenges and keep in air tight container.

RESULT

1. Physical Observation: The colour, odour, texture and taste of the lozenges were evaluated by direct observation.

Table no.3: Physical Evaluation

Weight Variation: Weight variation test is performed to calculate individual weight deviation from average weight calculated.

Weight Variation= Average weight-Individual weight/Average weight*100

Average weight = 15.930gm

Table no.4: Weight variation

Table no.5: Weight Variation

1. Friability: The friability of lozenges ia used to evaluate shock absorption during transportation and is determined by using roche friability tester

Initial weight= 7.690

Final weight= 7.620

%Friability= Initial weight- final weight *100 Initial   weight

=7.690- 7.620*100

            7.690

= 0.91%

Table no.6: Friability test

Hardness: Hardness of the lozenges is determined by monsento hardness tester

Table no.7: Hardness testing

Table no.8: Thickness and Diameter

1. Moisture Content: Moisture content of lozenges is determined to check its stability on exposure to moisture by using moisture balance apparatus
2. Weight of empty dish+ sample before drying(W1) = 65.21gm
3. Weight of empty dish+ sample after drying(W2) =65.18gm
4. Weight of sample= 1.690gm

%Moisture content= W1- W2*100

                                       W3

= 65.21-65.18*100

         1.690

= 1.7%

Table no.9: Moisture content test