1. INTRODUCTION:

In oral drug delivery, there are many scientific challenges that could be studied for years to come and breakthrough technologies are required to generate novel dosage forms raising drug delivery to higher level.⁽¹⁾ Oral drug delivery is the most flavoured route for the administration of various medications and tablets are the most widely accepted dosage form. Solid dosage forms are popular because of the ease of administration, accurate dosage, self-medication, pain avoidance, and most importantly patient compliance.

Among the major problems faced by many patients with conventional tablet dosage form is difficulty in swallowing. This problem is more apparent when drinking water is not easily available to the patient taking medicine. Dispersible tablet delivery system is characterized by fast disintegration, quick dissolving, rapid release and improved patient compliance. Difficulty in swallowing (dysphagia) is a common problem of all age groups, especially the elderly and pediatrics, because of physiological changes associated with those groups. Other categories that experience problems in using conventional oral dosage forms include the mentally ill, uncooperative and patients suffering from nausea, motion sickness, sudden episodes of allergic attack or coughing. Sometimes it may be difficult to swallow conventional products due to non-availability of water. These problems led to the development of a novel type of solid oral dosage form hence, an attractive, taste masking formulations are the need of the hour.⁽²⁾

1.1 Anatomy of Buccal Mucosa:

The buccal mucosa is comprised of the mucosal surfaces of the cheeks and lips, which form the anterolateral boundaries of the oral vestibule. It is contiguous with the mucosa that lines the floor of mouth and alveolar ridges. There are approximately 800–1000 minor salivary glands located throughout the buccal mucosa as well as other parts of the contiguous oral mucosa.⁽¹⁶⁾ The thickness of the epithelium in the buccal area in adult human is about 500-800m and of 100cm an average surface area. Buccal mucosa becomes recently a very attractive site for the administration of various Pharmaceutical dosage forms due to the potential benefits offered by this route.⁽³⁾

Figure 1: Anatomy of oral cavity.

Composition of Mucus Layer:

Mucus is a translucent and viscid secretion which forms a thin, contentious gel, mean thickness of this layer varies from about 50-450µm in humans secreted by the globet cells lining the epithelia or by special exoesive glands with mucus cell acini. It has the following general composition-

Water- 95%

Glycoprotein and lipids- 0.5-3.00%

Mineral salts- 1%

Free proteins- 0.5-1.0% ⁽⁴⁾

Advantages and Disadvantages of Drug Delivery Via the Oral Mucosa:

Conventional, have certain advantages. The oral mucosa is highly accessible and rapidly heals itself after trauma or damage. Such short recovery time reduces adverse drug effects induced by long-term topical drug delivery. The possibility of allergic responses is limited in oral mucosal delivery due to fewer Langerhans cells in the oral mucosa than the skin. The oral cavity is a highly hydrated envi-ronment that facilitates drug dissolution. Furthermore, the small surface area of the oral membrane is beneficial for sustained drug delivery, particularly for drugs of high potency. The oral mucosa is highly vascularized and there- fore allows the drug to gain direct access to systemic circulation via capillaries and venous drainage. Disadvantages associated with localized drug delivery to the oral cavity should also be considered. Saliva secretions may wash away the drug and/or dose form before absorption can occur. The delivery device may be dislodged by mastication and speech. Enzymatic degradation may retard absorption.⁽⁵⁾

1.2 Medicated Lollipop:

Lollipops are solid dosage forms, containing the medicament in a sweetened and flavored base, intended to dissolve slowly in the mouth. in the Lollipops have mainly contained the additives like sweetening agent, flavoring agent, the coloring agent, opacifier and stabilizing agent.⁽⁷⁾ medicated lollipops are slow dissolving delivery system .They dissolve in oral cavity within 1 to 10 minutes.⁽⁸⁾ Lollipops are large sugar boiled confectionary of various flavours attached to a plastic stick which can be consumed over a long period of time through licking. The plastic stick is used to hold the confection (medicament) together. Lollipops are solid unit dosage form of medicament which is meant to be dissolved in mouth (or) pharynx. Development of lollipops dates back to 20th century and is still in commercial production. Most of the lollipops preparations are available as over the counter medications. Lollipops provide a palatable means of dosage forms administration and enjoy its position in pharmaceutical market owing to its several advantages but it suffers from certain disadvantages too. They contain one (or) more medicament usually in a flavored, sweetened base. Lollipops are most often used for localized effects in the mouth. They can also be used for systemic effects if the drug is well absorbed through the buccal lining.⁽⁶⁾

History of Lollipops:

The idea of an edible candy on stick is very simple, and it is probable that the lollipops has been invented and reinvented numerous times. The first confectioneries that closely resemble what we call lollipops date to the middle ages, when the nobility would often eat boiled sugar with the aid of stick or handles. The invention of the modern lollipops is still something of mystery but a number of American companies in the early 20th century have laid claim to it. According to the book food for thought: extraordinary little chronicles of the world, they were invented by George smith of New Haven, Connecticut, who started making large boiled sweet mounted on stick in 1908. he named them after a racehorse of the time, lolly pop and trademarked the lollipop name in 1931. The term ‘lollipop’ was recorded by English lexicographer Francis Grose in 1796. The term derived from the term “lolly” means tongue and “pop” mean slap. The first references to the lollipop in its modern context date to the 1920. Alternatively, it may be a word of Romany origin being related to the Roma tradition of selling toffee apples sold on stick. Red apple in the Romany language is loli phaba.

Advantages of Medicated Lollipops:

1. Do not require water intake for administration. Technique is non-invasive and it is the case with parenteral.

2. Lollipops are early to prepare with minimum amount of equipment and time.

3. Lollipops can be given to those patients who have difficulty in swallowing.

4. Having formulas that are easy to change and can be patient specific.⁽⁷⁾

5. Bypass of the gastrointestinal tract and hepatic partake system, increasing the bioavailability of orally administered drug that otherwise undergo hepatic first-pass metabolism. In addition, the drug is protected from degradation due to pH and digestive enzyme of the middle gastrointestinal tract.⁽⁸⁾

6. It can reduce dosing frequency.

7. Systemic absorption of drug can be possible through buccal cavity.⁽⁹⁾

Disadvantages of Medicated Lollipops:

1. Heat labile drugs cannot be used in this formulation because of the high temperatures required for preparation.

2. Drugs having minimum bitter taste are suitable.

3. Heat stable drugs are suitable.⁽¹⁰⁾

4. For properly stabilization and safety of stable product ODT requires special packaging.

5. one important drawback of such dosage forms is ‘Dysphasia’ or difficulty in swallowing. This is seen to afflict nearly 35% of the general population. This disorder is also associated with a number of conditions like: parkinsonism, motion sickness, unconsciousness, elderly patients, children, unavailability of water⁽¹¹⁾

Mechanism of action of Medicated Lollipop:

With our lollipop delivery system, a drug is absorbed more rapidly through the mucosa of the mouth, than when the drug is swallowed and absorbed via the digestive system. The dose can be easily controlled by administering a lollipop until the desired effect is achieved. fun to consume. Additionally, they don’t require water, which means they can be taken anywhere and anytime.

How does it work?

Medicated lollipops release drugs slowly as a patient sucks or rotates a lollipop in the mouth. The medicine acts locally or systemically after absorption by buccal mucosa.⁽¹²⁾

Types of Medicated Lollipops:

Figure 2: Types of Medicated Lollipops

Hard Lollipop:

Hard lollipops might be considered solid syrups of sugars. These dosage forms are made by heating sugars and other ingredients together and then pouring the mixture into a mold. Hard lollipops are similar to hard candy. In fact, many hard lollipops formulas are modifications of hard candy formulas. The dosage form needs low moisture content. So water is evaporated off by boiling the sugar mixture during the compound process. Hard candy lollipops are mixtures of sugar and other carbohydrates in an amorphous (non-crystalline) (or) glassy condition.

These lollipops can be considered solid syrups of sugars and usually have a moisture content of 0.5% - 1.5%. Hard lollipops should not disintegrate but instead provide a slow, uniform dissolution (or) erosion over 30 minutes.

Soft Lollipops:

Soft lollipops have become popular because of ease with they can be extemporaneously prepared and their applicability to a wide variety of drugs. The base usually consists of a mixture of various PEGs, acacia (or) similar materials glycerol gelatin (or) an acacia: sucrose base. These lollipops may be coloured and flavored and they can be either slowly dissolved in the mouth (or) chewed, depending on the intended effect of the incorporated drug.⁽¹⁾

Types of delivery of medicated lollipop:

The medicated lollipop is often used in children to treat pain from painful surgery or diagnostic procedures. Medicated lollipops obviously comprise the incorporation of a drug into a candy matrix, which is subsequently placed in the buccal area. A proportion of the dissolved drug diffuses across the oral mucosa and is absorbed, while the remainder is absorbed or eliminated via the gastrointestinal tract. They are widely used for topical delivery in the oral cavity and systemic delivery into blood stream.

Types:

a. Medicated lollipops for local drug delivery.

b. Medicated lollipops for systemic drug delivery⁽⁵⁾

Suitable drug Candidate for Medicated Lollipop:

pediatrics, geriatrics and bedridden patients show inconvenience swallowing conventional tablets or capsules due to difficulties in swallowing with lesser amounts of water with the medication, unable to tolerate the taste of many drugs when formulated as liquid dosage forms, resulting in poor patient compliance. The medicated lollipops are flavoured medicated dosage forms intended to be sucked and hold in the mouth or pharynx. The illness are associated with fever headache and body aches so to cure the above, there was need to administer the drug to the individuals but in case of pediatric patients it was difficult to administer the dose forms like tablet, capsule, etc. These preparations are commonly used for the purpose of local effect or systemic effect. Medicated lollipops are prepared heating and congealing method. pediatrics are the most suitable candidate for he medicated lollipop. A small medicated candy intended to be dissolved slowly in the mouth to lubricate the irritated tissues of the tract. A small flavoured tablet made sugar (or) syrup and often medicated. A small medicinal tablet in the shape of lollipop is taken for sore throat. Lollipops are large sugar boiled confectionary of various flavours attached to a plastic stick which can be consumed over a long period of time through licking. The plastic stick is used to hold the confection (medicament) together Lollipops are the dosage forms that are intended to be dissolved slowly on the mouth (or), that can be easily swallowed are gaining popularity especially among paediatric patients. Lollipops are solid unit dosage form of medicament which is meant to be dissolved in mouth (or) pharynx. Development of lollipops dates back to 20th century and is still in commercial production. Most of the lollipops preparations are available as over the counter medications. Lollipops provide a palatable means of dosage forms administration and enjoy its position in pharmaceutical market owing to its several advantages.⁽⁶⁾

Excipient for Medicated Lollipop and their Functions:

Thousands of different excipients are used in medicines and make up, on average, about 90% of each product

The ideal characteristics of an excipient are given as:

· Chemically stable

· Non reactive

· Low equipment and process

· sensitive

· Inert to human body

· Non toxic

· Acceptable with regards to organoleptic

· characteristics Economical

· Having efficiency in regards with the intended use.

Method of preparation of Medicated Lollipop:

It was planned to prepare candy-based lollipops by heating and congealing method using specific polymer.

Heating and Congealing Technique

1. Firstly, dissolve the required amount of sugar to form a syrupy base by heating it at 1100C for 90 minutes.

2. Then add base syrup in it by raising the temperature to 1600C

3. Cooling to obtain the plastic mass.

4. After this, adding drug, polymer, colour, flavour into the syrupy liquid with mixing.

5. Size roping of the material in a moving roller is done after drying.

6. Wrapping the material with polyethylene wraps. ⁽⁶⁾

Evaluation of Medicated Lollipop

A) Physical Parameters

1. Hardness:

indicates the ability of a tablet to withstand mechanical shocks while handling the hardness of the tablets was determined using Monsanto hardness tester. It is expressed inkg/cm2. Three tablets were randomly picked and hardness of the tablets was determined

2.Friability (F)1:

Roche Friabilator was used for testing the friability. Twenty tablets were weighed accurately and placed in the tumbling apparatus that revolves at 25 rpm. After 4 min., the tablets were weighed and the percentage loss in tablet weight was Determined.

F = Wintial-Wfinal /Wintial× 100

3.Thickness and Diameter1:

Thickness and diameter was measured using Vernier Calipers. It was determined by checking the thickness and diameter of ten lollipops of each formulation. The extent to which the thickness of the each lollipop deviated from ± 5% of the standard value was determined.

4.Weight Variation:

Lollipops were randomly checked to ensure that uniform weight Lollipops were being made. 20 Lollipops formulations, weighed individually and average weight and % weight variation was calculated. The requirements are met if the weights of not more than 2 of the Lollipops differ from the average weight by more than the percentage listed in the accompanying table and no lollipops differs in weight by more than double that percentage. In present total weight of lollipop is 1000 mg. So, as per USP maximum difference allowed will be 10% for each lollipop.

5 Drug Content1:

Lollipops dissolved in 100 ml distil water and sonicated for 30 min and filtered. From the above solution 1ml was taken in volumetric flask and diluted up to 10ml (100μg/ml) and it was analyzed spectrophotometrically at 224 nm.

6 Moisture Content1:

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

7 Disintegration Test1:

Disintegration study performed by disintegration apparatus. Put one Lollipop into each tube suspend the assembly in the beaker containing pH 6.8 phosphate buffer and operate without the discs 30 min. Remove the assembly from the liquid. The lollipops pass.

8.Taste Masking Test1:

First the 10 health volunteers would be given to taste standard quinine solutions (20-160 mcg/mL) by swirling the solution in buccal cavity for 30 sec. and spitting out the solution. Volunteers would be asked to rank them on bitterness scale (rank 1-5). After 30 min., these volunteers would be asked to evaluate the taste of (drug) lollipop in the same manner and compare on the same scale. ⁽¹⁴⁾

9. In Vitro Dissolution Studies:

Dissolution rate was studied using USP II paddle dissolution apparatus, in 900ml of 37±0.5°at 100 rpm. Aliquot of dissolution medium was withdrawn at regular time intervals and the same volume of pre-warmed (37±0.5°) fresh dissolution medium was replaced. The samples were filtered and drug content of in each sample was analyzed after suitable Dilution

Uses of Medicated Lollipop:

Medicated lollipops are commonly used to treat problems such as infections and inflammation of the oral cavity. Topical preparations are often preferable to systemic meds due to the local effect. Advantages of using a medicated lollipop versus oral dosage forms include a reduction in gastric irritation, bypass of first pass hepatic metabolism and more rapid onset of action.

Lollipops can provide a retention time of up to 30 minutes in the mouth, compared to a conventional form of lozenges having a retention time of about 7 minutes. In particular, it is easier for a child to hold a lollipop in the mouth than it is to retain a lozenge.Oral thrush is a disorder caused by infection of the mouth due to the fungus (yeast) Candida albicans. Lollipops containing antifungal medications can provide an attractive alternative formulation in the treatment of oral thrush in pediatric patients.

Lollipops can be compounded for:

· Treatment of infection or inflammation

· Topical anesthetic

· Sedation

· Smoking cessation

· Nausea

· Pain relief.

Storage and packaging of Medicated Lollipop:

Packaging:

They 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 aluminum foil or cellophane membrane.

Storage:

They should be stored away from heat and out of reach of children. They should be protected from extremes of humidity. Depending up on the storage requirements of both, the drug and the base, either room temperature or refrigerator temperature is usually indicated. ⁽⁹⁾

Marketed Products:


Figure 8: Xyloburst Sugar Free Lollipops:	Figure 9: Yummy Earth Vitamin C Lollipops

Future Scope:

The global medicated confectionery market is growing at a CAGR of 3.8% during the forecast period (2020-2025).

· The market is mainly driven by the rising consumer preference towards a healthy lifestyle coupled with a shift in consumer taste preference and rising spending on confectionery products. Also, increasing prevalence of cough, cold, throat irritation and others remedy in the form of functional confectionery over the last few years. In addition, investments made by various industries High product innovation by the leading players such as sugar-free and organic chocolates are further contributing to the growth of the global market. In addition, frequent product launches play a vital role in the growth of the market. For instance, in April 2017, Mondelez International, owner of a popular medicated confectionery brand Halls launched Halls XS Honey Lemon, a new flavor to reinforce its Halls XS variant’s presence in Singapore.

· However, the decreased availability of the sugar substitutes and development of artificial sweeteners have shifted preferences of consumers towards artificial sweeteners and is thus restraining the market.

The global medicated confectionery market has been segmented by confectionery type into chocolate, snack bar, candy and sugar confectionery, and gum and mint; and by distribution channel into supermarket/ hypermarket, convenience stores, pharmaceuticals, online retail, and other channels. Also, the study provides an analysis of the medicated confectionery market in the emerging and established markets across the globe, including North America, Europe, Asia-Pacific, South America, and the Middle East and Africa. ⁽¹⁵⁾

CONCLUSION:

The formulation of medicated lollipop is an easy and time saving process. The medicated lollpops can provide an attractive, alternative formulation in treatment of pain in pediatric patients. The oral route of drug administration is the most preferred route of drug adminstration, patient compliance, ease of administration, and flexibility in formulation. Medicated lollipop is an ideal dosage forms for pediatric patients. ⁽⁶⁾This will offer better innovative dosage form. And enjoy an important position in pharmacy and will be remain at the same in future.⁽²⁾

REFERENCES:

1. Perumalla Jagadeesh, Padamasetty Jyothi i, G.Nethra Vani and S Dasthagiri. "Review of Medicated Lollipops" World Journal of Pharmaceutical Research 2017; 6(3); 399-405.

2. Rathode Minakshi, Poharkar Sachin,Pandhre Yuvraj, Muneshwar Monali, Sul Sandesh "Medicated Lozenges As An Easy To Use Dosage Form "World Journal Of Pharmaceutical Research 2018; 7(16); 305-322.

3. Misra Ambikanandan, Shahiwala Aliasgar, "Novel Drug Delivery Technologies", @ Springer Nature Singapore Pte Ltd 2019. 1-10.

4. Gandhi D.Sanket,Pandya R. Priyanka,Umbarkar Rahul, Tambawala Tanvi, Shah A. Manoj,"Mucoadhesive Drug Delivery System-An usual Maneuver For Site Specific Drug Delivery System" An International Journal of pharmaceutical science 2011;2(3); 132-152.

5. Kristian J. Tangso, Quy Phuong Ho and Ben J. Boyd* "Confectionery- Based Dose FORMS", Current Drug Delivery 2015; 12(3); 56-62

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Received on 27.12.2020 Modified on 05.01.2021

Res. J. Pharmacognosy and Phytochem. 2021; 13(1):33-38.

DOI: 10.5958/0975-4385.2021.00006.6

Sr. No.	Ingredients	Example	Role/Function
1.	Candy base Sugar Sugar free vehicles	Dextrose,sucrose,maltose,lactose,mannitol Sorbitol, PEG600and800.	These are the used as sweetening agent and impart the taste masking properties.
2	lubricants	Magnesium sterate, calcium sterate, stearic acid, and PEG, vegetable oils and fats.	These are used to avoid sticking of candy to the teeth.
3	Binders	Acacia, corn syrup, sugar syrup, polyvinylpyrrolidone, gelatin, tragacanth, and methylcellulose.	these are the used to hold particles.
4	coloring agent	Water soluble and lakolene dyes, FD andC colors, orange color pastered color cubes etc.	These are the used to inhance appearance and organoleptic properties of dosage form.
5	Flavorings agent	Menthol, eucalyptus oil, spearmint, cherry flavor etc.	These are the used to give a taste.
6	Whipping agent	Milk protein, egg albumin, gelatin, xanthan gum,strach, pectin, algin, and carrageenan.	These are the used in toffe-based confection.
7	Humectants	Glycerin, propylene glycol and sorbitol.	They improve chew mouth feel properties.⁽¹³⁾