INTRODUCTION:

Mouth ulcers are painful sores that canoccur anywhere inside the mouth. Thisleaflet is about the most common type of mouth ulcers, which are aphthous mouth ulcers. At least 1 in 5 people can develop aphthous mouth ulcers at some stage in their lives. Women are affected than male.

Lozenges are the flavoured medicated dosage forms intended to be sucked and held in the mouth or pharynx containing one or more medicaments usually in the sweetened base. Lozenges are intended to relieve oropharyngeal symptoms, which are commonly caused by local infections and also for systemic effect provided the drug is well absorbed through the buccal linings or when it is swallowed. Lozenges are used for patients who cannot swallow solid oral dosage forms as well as for medications designed to be released slowly to yield a constant level of drug in the oral cavity or to bathe the throat tissues in a solution of the drug. Drugs often incorporated into lozenges include analgesics, anaesthetics, antimicrobials, antiseptics, antitussives, aromatics, astringents, corticosteroids, decongestants, and demulcents. However, this is by no means an exhaustive list as many other drugs may lend themselves to delivery by lozenge. As well, both single and multi-ingredient lozenges can be compounded, depending on the particular patient's needs.

Table 1: Herbal Marketed Lozenges on treatment of mouth ulcer¹

Sr. No.	Trade name	Ingredients	Developer
1.	Sambucus Immune Lozenge	Elder berry extract, Vitamic C, Zinc gluconate	Nature's Way
2.	Horehound lozenges	Marrubium vulgare
3.	Halls	Menthole, eucalyptus oil, hexylresorcino	Mondelez International‎, ‎Cadbury-USA
4.	Koflet	Ginger, pepper, clove, licorice	Himalaya Drug company-India
5.	Golden Throat Lozenge	Honey Suckle Flower (jin yin hua), Peppermint Oil, Eucalyptus Oil, Luo-Han-GuoFruit, Tangerine Peel (juhong), Star Anise Oil, Sucrose	Solstice medicine company
6.	PhytoRelief-CC	Contains Turmeric, Pomegranate and Ginger	Alchemlife
7.	ViraBLOC	Elderberry extract	GNC

Advantages and disadvantages of Lozenges^2,3

Lozenges offer many advantages toeasily administer to geriatric and paediatric population It extends the time of drug in the oral cavity to elicit a specific effect, Easy to prepare, with minimum amount of equipment and time, it can be useful for those patient who have difficult to swallowing.

Medicated lozenges also have drawbacks like non-ubiquitous distribution of drug within saliva for local therapy and possible draining of drug from oral cavity to stomach along with saliva.

Classification of Lozenges⁴

Lozenges can be classified into various classes based on various methods like

1. According to the site of action

a. Local effect Ex. Antiseptics, Decongesants

b. Systemic effect Ex. Vitamins, Nicotine.

2. According to texture and composition

a. Chewy or caramel based medicated Lozenges are formulated by using heavy compression equipment to give a tablet that is harder than usual. Lozenges are usually flat faced with size of 5/8- 3/4 inch, weight 1.5- 4kg, hardness 30- 50kg inch2 and erosion time ranges between 5- 10 min.

b. Compressed tablet lozenges

c. Soft lozenges

d. Hard lozenges

1. According to the site of action⁵

Lozenges are classified into various classes based on various methods such as according to the site of action which can either be local or systemic effect. Examples of local effect are antiseptic, decongestion, while vitamins, nicotine are example of systemic effect.

2 According to texture and composition:

a. Chewy or caramel based medicated lozenges⁶

These are the dosage form in which medicament is incorporated into a caramel base which is chewed instead of being dissolved in mouth. These lozenges are especially used for pediatric patients. Most formulations are based on the glycerinated gelatin suppository formula which consists of glycerin, gelatin, and water. These lozenges are often highly fruit flavored and may have a slightly acidic taste to cover the acrid taste.

b. Compressed tablet lozenges⁷

Methods used for manufacturing of compressed tablets lozenges are direct compression methods and wet granulation method. Thermolabile drugs are suitable for formulation of compressed tablet lozenges. Lozenges tablets are differing as compare to conventional tablet in terms of organolepticity, non-disintegrating characteristics and slower dissolution profile. Lozenges are formulated by using heavy compression equipment to give a tablet that is harder than usual. Lozenges are usually flat faced with size of 5/8- 3/4 inch, weight 1.5- 4 kg, hardness 30- 50 kg inch2 and erosion time ranges between 5- 10 min.

c. Soft lozenges⁷

Polyethylene glycol 1000 or 1450, chocolate or sugar acacia base are used as base in the soft lozenges formulation and they give soft texture to the lozenges. Some soft lozenges contain acacia and silica gel. Silica gel is used as suspending agent to avoid settling of materials to the bottom of the mould cavity during the cooling. They are formulated by using hand rolled method to get desired size as well as thickness and cut in to pieces or the warm mass poured into a plastic mould to get soft lozenges. The formulation requires heating process at about 50oC hence is only suitable to heat resistant ingredients.

· Base: Polyethylene glycol 1000, Polyethylene glycol 1450, chocolate, sugar acacia base.

· Suspending agent: silica gel. Etc.

d. Hard lozenges^3,4

These are mixtures of sugar and other carbohydrates in an amorphous (non crystalline) or glassy state. They can also be regarded as solid syrups of sugars. The moisture content and weight of hard candy lozenge should be in between, 0.5 - 1.5% and 1.5-4.5g respectively. These should undergo a slow and uniform dissolution or erosion over 5- 10 min., and they should not disintegrate. Disadvantage: The temperature required for their preparation is high hence heat labile materials cannot be preparing

Formulation of Herbal Lozenges⁷

Lozenges are formulated in such a way that they are stable, provide a good medium for administration of drugs. The ingredients which are used for formulation of Lozenges are as shown in table.

Table 2: Common formulation of herbal lozenges

Ingredient	Example
Candy base 1. Sugar 2. Sugar free vehicles 3. Other fillers	Sucrose, Maltose, Lactose, Dextrose Sorbitol, Mannitol, Polyethylene glycol 600 and 800 Calcium carbonate, di calcium phosphate, calcium sulphate, Microcrystalline cellulose
Binders	Acacia, corn syrup, sugar syrup, gelatin, polyvinyl pryyolidone, tragacanth and methylcellulose.
Lubricants	Magnesium stearate, calcium stearate, stearate acid and PEG, vegetable oils and fats.
Coloring agents	Water soluble and lakolene dyes, FD and C colours, orange colour and paste, red colour cubes, etc.
Flavorings agents	Menthol, eucalyptus oil, spearmint, cherry flavour, etc.
Whipping agent	Milk protein, egg albumin, gelatin, xanthan gum, starch, pectin, algin and carrageenam.
Humectants	Glycerin, Propylene glycol and Sorbitol

Table 3: Herbal drug used for treatment of mouth ulcer

Activity	Drugs
Analgesic	Clove Peppermint essential oil.
Anti-inflammatory	Lemon oil Turmeric Peppermint essential oil
Anti-microbial	Clove Turmeric
Anti-septic	Turmeric Peppermint essential oil
Anti tussive	Cardamom Gum Arabic
Anaesthesia	Clove Cinchona Ginseng
Astringents	Liquorice Alum Acacia
Corticosteroids	Ashwagandha Fenugreek
Decongestant	Peppermint essential oil Eucalyptus oil
Demulcents	Glycerine Liquorice

Method of preparation of Herbal Lozenges^8,9

The methodology Include-Heating and congealing method.

General method of preparation:

Procedure:

We prepare herbal lozenges by heating and congealing method. We prepare syrupy base by dissolving the required amount of sugar by heating at 110^oC for about 90 minutes. Then we allow the base to cool down to obtain a plastic mass. Then we add active drug ingredients (clove oil, turmeric powder, peppermint oil, lemon oil, and aloevera), colouring agent (indigo carmine) and preservatives. All the ingredients are mixed thoroughly to form a uniform mixture. Then pour the mixture into mould of desired shape and allow to cool it at room temperature. After the formation of lozenges, they are wrapped in a polyethylene wraps.

Evaluation of lozenges:¹⁰

All the formulation prepared were subjected to different evaluation parameter as subjected below.

A. Quality control:

1. Candy base:

For the candy base it is essential to check for corn syrup and sugar delivery gears temperature; steam pressure; cooking speed; temperature and vacuum of candy base cooker.

2. Macroscopical evaluation:

The formulation developed in the laboratory were evaluated for its acceptance based on visual observation for various organoleptic properties. Such as

· Colour

· Odour

· Taste

· Texture

· Shape

3. Determination of ash value:

The total ash method is designed to measure the total amount of material remaining after ignition. This includes both “physiological ash”, which is derived from the plant tissue itself, and “non-physiological” ash, which is the residue of the extraneous matter (e.g. sand and soil) adhering to the plant surface.

4. Moisture contain analysis:

The sample was weighed and crushed in a mortar. From this, one gram of the sample was weighed and placed in a desiccator for 24 hours. After 24 hours the sample weighed. The moisture content is determined by the abstracting the final weight from initial weight of lozenges.

Moisture content = Initial weight – Final weight

B. Physical and chemical testing:

1. Diameter and thickness:

Diameter of the candy is important for uniformity of lozenges size. It can be measured using Vernier Callipers. The extent to which the diameter of the lozenges deviated from ± 5% of the standard value.

2. Friability test:

The friability of the 20 tablets from each batch was tested by a fribilator. At a speed of 25 rpm for 4 min. The lozenges were then deducted, reweighed and percentage weight loss was calculated by the equation,

(initial Wt. - Wt. after friability)

% Friability = –––––––––––––––––––––––––––– × 100

initial Wt.

3. Hardness test:

To evaluate the diametrical crushing strength, 3 tablets from each formulation were tested using a MAC hardness tester. The mean±SD values were calculated

4. Average weight and weight variation test:

20 lozenges were selected and weighed collectively and individually on an electronic balance. From the collective weight, average weight was calculated. Each lozenge weight was then compared with average weight to assure whether it was within permissible limits or not. Not more than two of the individual weights deviated from the average weight by more than 7.5% for 300 mg tablets and none by more than double that percentage.

weight of 20 lozenges

Average weight = ––––––––––––––––––––

average weight – weight of each tablet

% weight variation = –––––––––––––––––––––––––––– × 100

Average weight

C. Microbial Test for Lozenges:

In this, the presence of any bacterial, mould or spore contamination is checked in raw materials, finished products, machinery, cooling tunnels, environmental conditions and storage drums. Laboratory microbial testing should include the following counts:

· Total plate

· Total coliform

· Yeast and mold

· E. coli

· Staphylococcus

· Salmonella

D. Stability Testing of Product:

Lozenges are subjected to stability testing under following conditions:

· 1-2 months at 60°

· 3-6 months at 45°

· 9-12 months at 37°

· 36-60 months at 25° and 40°

Stability testing of product in package Lozenges in their final packs are subjected to following conditions for stability testing:

· 25° at 80% RH for 6-12months

· 37° at 80% RH for 3 months

· 25° at 70% RH for 6-12 months

Packaging:

Since the lozenges are hygroscopic in nature a complex and multiple packaging is adopted. The individual unit is wrapped in polymeric moisture barrier material which are then placed in tight or moisture resistant glass, polyvinyl chloride or metal container that is over wrapped by aluminium foil or cellophane membrane.

Storage:

Lozenges should be stored away from heat and out of reach of children. They should be protected from extremes of humidity. Depending upon the storage requirements of both, the drug and the base, either room temperature or refrigerator temperature is usually indicated.

CONCLUSION:

From this review it is clear that herbal lozenges play a vital role in the treatment of mouth ulcer. The anti-ulcer activities probably due to the presence of flavonoids in herbal plants due to their better compatibility with human body and lesser side effects. The herbal medicine is the best choice for the treatment of mouth ulcer due to the presence of chemical constituents which are naturally available and with their great uses and healing effects. This concept will be more acceptable in future for symptomatic treatment of mouth ulcer.

REFERENCE:

1. https://innovareacademics.in/journals/index.php/ijap

2. Deepak R, Sanjay S. Formulation and evaluation of antianthalmentic Chewable tablet. Int Pharma Sciencia. 2012; 2(1): 13-26.

3. Allen LV. Troches and lozenges, SecundumArtem. Current and Practical Compounding Information for the Pharmacist. 2001; 4(2): 23-25.

4. Peters D. Medicated lozenges. In: Lieberman HA, Lachman L, Schwartz JB editors. Pharmaceutical Dosage Forms: Tablets, 2nd Ed. New York: Marcel Dekker, Inc. 2005: 419-577.

5. Stephen O. Majekodunmi, a Review on Lozenges, American Journal of Medicine and Medical Research, 2015; 5(2): 99-104.

6. SV Sastry, JR Nyshdham, JA. Reviw of formulation used in oral cavity. Pharm Sci and Technol Today. 2000; (3): 138-145

7. MinakshiRathod*, Sachin Poharkar, YuvrajPandhre, MonaliMuneshwar, SandeshSul “Medicated lozenges as an easy to use dosage form” World Journal of Pharmaceutical Research SJIF Impact Factor 8.074 Volume 7(16): 305-322.

8. Kamlendra Kumar Mishra, KutubuddinTasneem, Vikas Jain, S.C. Mahajan “Formulation and Evaluation of Herbal Lozenges” Journal of Drug Delivery and Therapeutics. 2017; 7(7): 87-89.

9. SuchitaPundir, AbhayMurari Lal Verma “Review on Lozenges” Journal Der PharmazieFershung, 2014; 2(1): 1-10.

10. Pundir S, Verma A.M. “Formulation Development and Evaluation of Antiemetic Lozenges of Ondansetron Hydrochloride”, 3(3): 365-372.

Received on 04.10.2021 Modified on 17.12.2021

Asian J. Pharm. Res. 2022; 12(2):162-166.

DOI: 10.52711/2231-5691.2022.00025