INTRODUCTION:

Mouth ulcer is one of the common disorders caused due to variety of etiological factors. The two most common causes of oral ulceration are local trauma (e.g. rubbing from a sharp edge on a filling) and aphthous stomatitis ("canker sores"), a condition characterized by recurrent formation of oral ulcers for largely unknown reasons. Mouth ulcers often cause pain and discomfort, and may alter the person's choice of food while healing occurs. This studied focuses on various herbal remedies for the treatment of mouth ulcer.¹

Lozenges are solid preparations that contain one or more medicaments, usually in a flavoured, sweetened base, and are intended to dissolve or disintegrate slowly in the mouth or these are medicated candy intended to be dissolved slowly in the mouth to lubricate and sooth the irritated tissues of throat. Lozenges are one of the widely used dosage forms. The benefits of the medicated lozenges are they increase the retention time of the dosage form in oral cavity which increases bioavailability, reduces gastric irritation and bypasses first pass metabolism.²

Lozenges provide a palatable means of dosage form administration and enjoy its position in pharmaceutical market owing to its several advantages. This dosage form can be adopted for local as well as systemic therapy and a wide range of active ingredient can be incorporated in them lozenges or troches are experiencing a renewed popularity as a means of delivering many different drug products.²

Different types of lozenges and their methods of preparation along with ingredients used in their preparation are discussed. Drug candidates which can be incorporated in lozenges include antiseptics, local aesthetics, antibiotics, anti-allergics, anti-inflammatory, analgesics, anti- ulcerative, astringent. The selection criteria for flavouring agents are mentioned, quality control tests of lozenges have been reviewed. The present study covers more or less all aspects associated with lozenges.

Oral dosage form is more reliable than any other dosage form. They are natural and easiest route of drug administration. They are the most frugal and safest form for the patient. No nursing is required, which means the patient can take the oral dosage form by its own.

Lozenges are solid dosage form that are intended to hold in oral cavity and wetted with saliva to slowly dissolve or disintegrates in mouth and give its local effect.

Lozenges are a type of medicaments found in different shapes and colours. They are a small flavoured tablet made from sugar or sugar base. It is well absorbed in buccal lining and pharynx.

Dissolution time of lozenges:

· Lozenges dissolution time is 20-30minute

· Dissolution also depends on the patient, as patient controls the rate of dissolution and absorption by sucking the lozenges until it dissolves in mouth completely.

· Lozenges maximize the local activity of drug as it remains in our oral cavity for long time

· Lozenges plays an important role for treating mouth ulcer

· Mouth ulcer: -This is one of the most common oral problem which is characterized by a loss of mucosal layer inside the mouth & it can arise a number of disorder.

· Mouth ulcer is a painful sore on inner lips, gums, tongue, and roof of the mouth or throat that may interfere with eating because it causes irritation, redness, inflammation and pain. Lozenges are used to treat this mouth ulcer as it reduces the pain and inflammation of ulcer and remain in mouth for a long haul to heal it rapidly.

Types of lozenges:³

1) Medicated lozenges: eg. Strepsils

2) Non-medicated lozenges: eg. lollipops and candies.

1) Medicated lozenges are classified into three types:

I) Hard lozenges

II) Soft lozenges

III) Chewable lozenges

I) Hard lozenges:

Hard lozenges are generally formed using sucrose or other sugars similar to the process for hard candy confections that produce a hardened amorphous glassy material. To slow the rate of dissolution, polymers such as PEGs and HPMC may be added. Another type of hard lozenge may be made of compressed powders. An example of this is clotrimazole troches (lozenges) made as a large compressed tablet that is slowly dissolved in the mouth. The tablet base material is made of dextrose, MCC, and povidone.

II) Soft lozenges:

Soft lozenges are often made using PEGs of sufficient molecular weight to provide slow dissolution in the saliva. Additionally, hydrocolloids such as acacia may also be added as an adhesive agent. Soft clotrimazole troches can be made this way by adding drug and acacia to melted PEG 1450 base and pouring into troche moulded cavities.

III) Chewable lozenges:

Chewable lozenges are typically based on glycerinated gelatin; a base of glycerine, gelatin, and water. This base can be mixed with drug,

2) Non-medicated lozenges:

1) Lollipops: A lollipop is a type of sugar candy usually consisting of hard candy mounted on a stick and intended for sucking or licking. Different informal terms are used in different places, including lolly, sucker, sticky-pop, etc. Lollipops are available in many flavours and shapes.

2) Candies: It is a Non-medicated type of lozenges of various contrasting colours made from sugar syrup by filling the syrup with different flavours in different moulders for different shapes.

History of lozenges:

The word lozenge comes from the Old French word 'losenges' meaning 'diamond shape'. Its use in describing a shape dates back to the early 14th century. Sometime during the 1520s, lozenge began to be used to refer to 'a tablet of medicine, held in the mouth and dissolved'.

Like many prevailing medicines, lozenges originated in Ancient Egypt, specifically 1000 BC. Then, they were often made of honey, with flavours ranging from citrus to spice. IN the 19th century, physicians discovered morphine and heroin, which suppress coughing at its source—the brain. Popular formulations of that era included Smith Brothers Cough Drops, first advertised in 1852, and Luden's, created in 1879. Concern over the risk of opioid dependence led to the development of alternative medications.

MATERIALS AND METHODS:

Lozenges can be prepared by heat and congealing method with addition of sugar syrup and dextrose. Moulded lozenges are sometimes referred to as pastilles, whereas compressed lozenges may be referred to as troches. They 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 bath the throat tissues in a solution of the drug. Lozenges historically have been used for the relief of minor sore throat pain and irritation and have been used extensively to deliver topical anaesthetics and antibacterial. Today they are used for of drugs like analgesics, anaesthetics, antimicrobials, antiseptics, antitussives, aromatics, astringents, corticosteroids, decongestants, and demulcents and other classes and combinations.^2,3

Material:

Amoxicillin tablet was brought from the Vikas Medical Store, Gondia. Turmeric (Curcuma longa), Clove Buds (Syzygium aromaticum), Guava Leaves (Psidium guajava), Liquorice (Glycyrrhiza glabra), Tulsi(basil) leaves (Ocimum tenuiflorum), Pigeon pea leaves (Cajanus cajan), Mint (mentha piperita) were brought from the Local Market, Gondia.Gava Leaves were collected from Medical Garden of MIBP, Gondia. All the chemical use is of analytical Grade.

Materials Used For Preparation of Herbal Lozenges:

· Turmeric (Curcuma longa)

· Clove Buds (Syzygium aromaticum)

· Guava Leaves (Psidium guajava)

· Liquorice (Glycyrrhiza glabra)

· Tulsi(basil) leaves (Ocimum tenuiflorum)

· Pigeon pea leaves (Cajanus cajan)

· Mint (mentha piperita)

Method of isolation of herbal extract:

Isolation of curcumin from turmeric⁴:

Curcumins or curcuminoids are the diaryl heptanoid compounds obtained from the dried rhizomes of Turmeric, Curcuma longa family, Zingiberaceae. It is a major colouring principle present up to 5% in the rhizomes, which constitutes about 50–60% of the mixture of three maincurcuminoids namely curcumin, desmethoxycucumin and bisdesmethoxycurcumin. The standardized extract of turmeric contains major proportion of the above curcuminoids. Commercial curcumin isolated from turmeric rhizome contains up to 97% pure product.

Curcumin can be obtained by different processes. Turmeric powder is extracted with alcohol in soxhlet extractor. The alcoholic extract is concentrated under reduced pressure and dried. In another procedure, turmeric powder is first extracted with hexane followed by acetone. The acetone extract is concentrated and dried to yield curcumin. The most efficient way of isolating curcumin was found to be to extract with hot ethanol, concentrate the filtrate, and throw the concentrate into superior grade kerosene, when a solid mass separates. The mass is stripped off kerosene with petroleum ether and re-crystallized from ethanol. The final product obtained is re-crystallized from hot ethanol to yield orange-red needles.

Melting point:

Curcumin 183°C, desmethoxycucumin 168°C, and bisdesmethoxycurcumin 224°C

Thin Layer Chromatography of Curcumin:

Dissolve 1mg of curcumin in 1 ml methanol. Apply the spots on silica Gel-G plate and elute the plate in the solvent system chloroform–ethanol–glacial acetic acid (94:5:1). Dry the eluted plate and visualize under 366 nm light. Curcumin exhibits a bright yellow fluorescent spot at RF value 0.79. The other spots appearing at RF values 0.60 and 0.43 correspond to desmethoxycurcumin and bisdesmethoxycurcumin

Isolation of eugenol⁵:

Eugenol is a 4-allyl-2-methoxy phenol obtained from the essential oil of clove buds Eugenia caryophyllus; family Myrtaceae. It is also obtained from Cinnamon leaf oil obtained from Cinnamomum zeylanicum; family Lauraceae. Both of the oils contain 80–90% eugenol.

Dried clove buds are hydro distilled to yield the clove oil. Being heavier than water it makes a layer beneath water. The lower er of clove oil is separated from water. For the separation of eugenol from clove oil, the oil is dissolved in solvent ether to make about 10% solution. It is shaken with three successive volumes of 10% potassium hydroxide solution. Eugenol being phenolic compound gets converted to phenoxide and becomes soluble in water. The total aqueous alkaline extract is combined and washed with fresh ether to remove other impurities. Eugenol is regenerated by acidifying the aqueous alkaline extract with excess of sulphuric acid. The acidified solution is extracted in separating funnel with three successive volumes of solvent ether. The combined solvent ether extract is then washed with water. Ether is removed by distillation at very low temperature to yield pure liquid eugenol.

Boiling point: 255°C

Thin Layer Chromatography of Eugenol:

Dissolve about 1 mg of eugenol in 1 ml of methanol and apply the spots over silica gel-G plate. Elute the plate with pure benzene as a solvent system. Spray the dried plate with 1% anisaldehyde-sulphuric acid reagent and heat the plate at 110°C for 10 min. Eugenol shows the spot with dirty green colour at Rf 0.40 in case of normal chamber saturation at 24°C.

Extraction guava leaves^6:

Sampling processing

Fresh green leaves of guava (Psidium guajava) tree were collected from the premises of Vignan’s Foundation for Science, Technology and Research, Vadlamudi, Guntur, Andhra Pradesh. The leaves were gently rinsed with water, sundried to remove the moisture and powdered using a blender. The powder was then passed through aluminium sieve of (1mm) to get uniform particle size. Guava leaf powder was stored in an air tight container for further studies.

Guava leaf extraction procedure:

The guava leaf powder (25g) was suspended in ethyl acetate (100mL) and stirred for 24 h under sterile conditions (Seo et al. 2014). The extract was filtered using Whatman no. 1 filter paper and the filtrate was used for identification of various phytochemicals/bioactive compounds based upon the retention time and mass spectra of the library retrieved from National Institute of Standards and Technology (NIST).

Isolation of glycyrrhizin⁷:

The isolation of glycerrhizin from glycerrhiza is based onits solubility. Glycerrhizin is soluble in hot water, alcohol, but slightly soluble in cold water andinsoluble in ether.

Alcohol extraction method Procedure:

1. Weigh 50g of powdered drug into 500ml beaker & add 100mlmethanol mix it.

2. Add another 100ml methanol& left for 24hrs.

3. Filter and collect the filtrate

4. Extract this methanolic extract with 3 portions of petroleum ether, subsequently with benzene, ethyl acetate chloronium andsolvent ether.

5. Transfer methanolic layer into china dish & evaporate on water bath to get glycyrrhizin.

METHOD OF FORMULATION OF LOZENGES:

By heat and congealing method: -

Sufficient quantity of sugar was blended with water to form sugar syrup. Dextrose was dissolved in a little quantity of water and heated at 100°C until it convert into clear transparent viscous solution. Pour dextrose solution into sugar syrup by applying heat up to 150°C until golden yellow colour obtain. Stand solution for 5min, after that mix all polymer and all herbal extract with solution to achieve perfect size of lozenges, pour it into the moulding pan. Then packed lozenges with aluminium foil and place it in desiccators to shield it from moisture.^8,9,10

Table 1. Formula for preparation of herbal lozenge with sugar base

SR. NO.	INGRIDEINTS	QUANTITY TAKEN
1	Sugar	2.5gm
2	Dextrose	1gm
3	Mint	1gm
4	Turmeric	1ml
5	Clove buds	1ml
6	Guava leaves	3ml
7	Liqorice	1ml
8	Tulsi(basil) leaves	1ml
9	Pigeonpea leaves	3ml

Figure 1. Final formulated herbal lozenge with sugar

Figure 2. Marketed lozenges

Preparation of lozenges using gelatin as base:

Take gelatin in the form of a warm 10% aqueous solution. Then add sufficient quantity of sugar with water by heating it up to 100°c until it convert to transparent viscous solution. Stand the solution for 5min after that add all the herbal extracts in It and mix it vigorously to form a homogeneous solution after that pour all the solution in a moulding pan to obtained perfect size of lozenges.¹¹

Table 2. Formula for preparation of herbal lozenge with gelatine base

Sr. No.	Ingredients	Quantity TAKEN
	Ingredients	F1	F2	F3	F4	F5	F6
1	Gelatin (10%)	31.7gm	31.7gm	31.7gm	31.7gm	31.7gm	31.7gm
2	Sugar	2.5gm	2.5gm	2.5gm	2.5gm	2.5gm	2.5gm
3	Mint	1gm	1gm	1gm	1gm	1gm	1gm
4	Turmeric	1ml	1ml	1ml	1ml	2ml	3ml
5	Clove buds (oil	1ml	1ml	1ml	1ml	2ml	3ml
6	Guava leaves	2ml	2ml	2ml	1ml	2ml	3ml
7	Liqorice	3ml	3ml	3ml	1ml	2ml	3ml
8	Tulsi(basil) leaves	1ml	1ml	1ml	1ml	2ml	3ml
9	Pigeonpea leaves	3ml	3ml	3ml	1ml	2ml	3ml

Figure 3. Final formulated herbal lozenges with gelatin

EVALUTION LOZENGES^12,13:

There are various evaluation parameter for the herbal formulated lozenges like thickness and diameter, friability, weight variation, disintegration time, in-vitro dissolution studies, antimicrobial studies.

Thickness and diameter:

Diameter ad thickness is a physical property of tablet and it should be essential for patient acceptance as well as for tablet uniformity. It is calculated by using vernier scale and measured in mm.

Hardness test:

To check the hardness of prepared lozenges we use Pfizer tester.

Friability test:

Friability testing is method which is employed to determined physical strength of lozenges by using Roche friabilator were we placed 6 tablet in friabilator and subjected to revolve at speed of 25rpm up to 10 revolutions then further weight the tablet and calculate the % friability.

Weight variation test:

Weight variation where determined by calculating average weight of 20 tablet by comparing the weight of each lozenge with average weight.

Disintegration time test:

For determination of disintegration time placed 6 tab in disintegrating apparatus and revolve at to 29 to 32 cycle per minute at PH 6.8 phosphate buffer contain 15% starch.

In vitro dissolution:

In vitro dissolution test was conducted with help of USP dissolution apparatus type II (paddle) at 100 rpm and 37°± 5°cat PH 6.8 phosphate buffer solution containing 15% starch used as dissolution medium for dissolution apparatus.

Stability testing:

The stability study of herbal lozenges was performed at 38°C±8°C/ 70±5% RH and 25°C±8°C/ 60±5% RH respectively for months and the formulation of lozenges were examined visually for physical changes. The drug content was also determined at the end of every month for 3 months.

Antimicrobial activity:

The antimicrobial activity checked by using cup plate technique, in cup plate method azithromycin solution diffused into the agar layer containing micro-organism, the zone is formed around the cylinder.

Again at another cylinder diffused saline water for control and mixture of herbal drug extract for testing antimicrobial activity and we get result, were blank preparation shows zone of inhibition as well as mixture of herbal drug extract.

RESULT AND DISCUSSION:

Weight Variation Test:

The specified IP limit for percentage weight variation of lozenges is varied between 0.98% - 1.21%. The range of hardness is found in between 5.5kg/cm 2-13.5kg/cm2. And friability of lozenges should be less than 1% which shows better stability during handling. Disintegration time ranges in 35min - 36min. Hence it is concluded that the below result values of respected evaluated parameters are found within the limit.

Antimicrobial Activity: -

The prepared lozenges show antimicrobial activity when tested microbiologically by cup plate method using Penicillin solution as a standard, Herbal extract as a test solution and distilled water as a blank.

Figure 4. Zone of inhibition of Marketed formulation (Azithromycin)

Figure5. Zone of inhibition Control (saline water)

Figure 5. Zone of inhibition of herbal prepared lozenge

Table 4. Zone of Inhibition.

Sr. No.	Zone Of Inhibition
Sr. No.	Markated Formuation (azithromycin)	Herbal preparation lozenges	Controle (Saline Water)
F1	2.6	1.8	No zone of inhibition
F2	3.0	2.5	No zone of inhibition
F3	2.8	2.3	No zone of inhibition
F4	2.4	2.5	No zone of inhibition

Stability Studies:

The stability study was observed that there is no change in physical appearance of formulation. There is no significant change in the physical parameter like Weight Variation, Hardness, Friability, Disintegration time, Thickness and Diameter, in-vitro dissolution studies. And the given result conforms that the formulation is stable at respective temperature.

Table 5. Stability data of optimized formulations

Sr. No.	Time interval	Hardness Kg/cm² (n=3)		Friability (%) (n=6)
Sr. No.	Time interval	F2	F4	F2	F4
1	After 1 month	10.1	7.32	0.92	0.89
2	After 2 months	9.11	7.23	0.98	0.92
3	After 3 months	9.9	7.16	0.97	0.90

CONCLUSION:

From recent work it was assured that the herbal lozenges can be considered as a reliable delivery system for the treatment of mouth ulcer. Lozenges are intended to dissolve slowly in the mouth and remains in the mouth for prolonged period of time therefore it shows better and quick action in the treatment of Mouth Ulcer.

ACKNOWLEDGEMENT:

This research was supported by Principal of Manoharbhai Patel institute of Gondia. We thank to our Principal Manisha U. Mishra for their support in research work.

REREFENCES:

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Received on 12.05.2022 Modified on 24.09.2022

Asian J. Pharm. Tech. 2023; 13(1):19-24.

DOI: 10.52711/2231-5713.2023.00004

Sr. No.	Formulations	Weight variation (n=20)	Hardness Kg/cm²(n=3)	Thickness mm(n=3)	Friability (%) (n=6)	Disintegration time (min)
1	F1	1.16	9.1	3.08	0.84	44
2	F2	1.13	10.4	3.02	0.96	51
3	F3	1.05	11.5	2.56	0.82	55
4	F4	1.02	12.6	3.12	0.15	56
5	F5	1.14	13	3.06	0.06	40
6	F6	0.99	13.5	3.07	0.13	41