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Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89.

Review Article CODEN: IJRPJK ISSN: 2319 – 9563

International Journal of Research

in

Pharmaceutical and Nano Sciences Journal homepage: www.ijrpns.com

AN OVERVIEW ON MEDICATED CHEWABLE LOZENGES

M. P. Subash Chandran*1, G. P. Prasobh 1, P. Aparna 1, T. S. Arun 1, Sonia Ninan 1, S. Saranya 1

1*Department of Pharmaceutics, Sree Krishna College of Pharmacy and Research Centre, Parassala, Thiruvananthapuram, Kerala, India.

ABSTRACT Oral solid dosage forms is the most widely use dosage forms for their easy mode of administration and many other advantages when compared to other conventional dosage forms. Under oral dosage forms, lozenges play a vital role in delivery of drugs to the patients. Lozenges are flavoured solid with one or more medicament, in a sweetened base and are intended to dissolve or disintegrate slowly in the mouth. They are medicated which are to be dissolved slowly in the mouth to sooth and lubricate the irritated tissues of throat. They are intended to produce local as well as systemic effect. Although they have many advantages, they have disadvantages too. Lozenges are of different types and are manufactured by different methods. Various types of synthetic as well as herbal lozenges are available in the market. The formulation and quality control tests of lozenges have been discussed in this review. Not only in children, in adults too, the acceptance ratio for lozenges as a dosage form is high.

KEYWORDS Lozenges, Caramel based medicated lozenges, Hard lozenges and Soft lozenges.

INTRODUCTION Lozenges are prepared as single solid dose Author for Correspondence: medication, producing a local effect in the oral cavity and the throat, which is intended to be sucked Subash Chandran M P, in mouth. The active substances mixed with a Department of Pharmaceutics, flavored and sweetened base dissolve or disintegrate Sree Krishna College of Pharmacy and Research Centre, slowly inside the mouth 1. Lozenges give Parassala, Thiruvananthapuram, Kerala, India. smoothening effect to the throat and they release the medicament slowly in a constant rate remaining in Email: [email protected] the mouth. For the patients who find difficulty in swallowing of solid oral dosage form, lozenges remain as a best dosage form. A

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Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89. includes troche, cachou or cough sweet, cough drop, • They can be easily administered to children which is small, medicated , intended to be and old age people. dissolved slowly in mouth to temporarily arrest • The contact time of lozenges in the oral coughs, to lubricate and to soothe the irritated cavity is more to produce the specific effect. tissues of the throat infections caused due to • Sweeteners and flavors can be used to mask and . the bitter taste of the drug used in Chewable lozenges are intended to treat local formulation. irritation or infection of mouth or pharynx and may • It can increase bioavailability. also be used for systemic drug absorption. They are • Since drugs are systemically absorbed in 2 commonly used by children and old age patients . buccal cavity, it reduces absorption time. Lozenges produce local effect by soothing and • There is no need for disintegration of purging the throat. Systemic effect is produced by lozenges. lozenges by the absorption of drug through the buccal linings or when it is swallowed. Lozenges DEMERITS 7 are taken in oral cavity. Because of their size, • Drugs drain from oral cavity to stomach sublingual lozenges are impractical. Buccal along with saliva without producing lozenges are formulated and extensively used by required action. placing between the cheek and the gums. Though • The lozenges require high the lozenge dissolution time is about 30 minutes, temperature for their preparation. this depends on the patient; as the patient controls • Aldehyde candy bases are not suitable for the rate of dissolution and absorption by sucking on certain drugs e.g. . lozenge until dissolves. Subsequent production of • saliva and sucking also leads to increased dilution The non- uniformity drug distribution within of the drug and accidental swallowing of lozenges 3. saliva affects the local therapy. • Lozenges are prepared by molding method or fusion Accidental intake of the lozenges dosage method and by compression method. Molded or form by children as candy can lead to fused lozenges are also known as , whereas serious effects. compressed lozenges are also known as troches. 8-10 They are used for patients to bath the throat tissues FORMULATION OF LOZENGES in a of the drug. Since long time lozenges The formulation of lozenges normally includes are used for the relief of minor pain and Candy base, lubricant, binder, colouring adent, irritation. They are also used to deliver topical flavouring agent, whipping agent and humectants. anesthetics and antibacterial agents. Now a days the Candy base use of lozenges has spread wide for drugs like Candy base consists of sugar, sugar free vehicle and anesthetics, antimicrobials, analgesics, antiseptics, fillers. Dextrose, sucrose, maltose and lactose are antitussives, astringents, corticosteroids, aromatics, commonly used sugars. Sugar free vehicles includes decongestants, and demulcents and other classes mannitol, sorbitol, polyethylene glycol (PEG) 600 and combinations 4. and 800. Di calcium phosphate, calcium sulphate, calcium Carbonate, lactose and microcrystalline MERITS 5,6 cellulose are common fillers. • Lozenges are easily administered to patients Lubricants who have difficulty in swallowing. Magnesium stearate, calcium stearate, stearic acid, PEG, vegetable oil and fats. • They can reduce dosing frequency by

producing long term release of medicament.

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Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89. Binders absorption and systemic use. “The gummy-type” Binders are added to obtain uniform shape and candy lozenge is commonly used for children. flexibility to the preparation. Binders such as These are gelatin based pastilles were prepared by Acacia, corn , sugar syrup, gelatine, polyvinyl pouring the melt into molds or out onto a sheet of pyrrolidone, tragacanth, methyl- cellulose, etc are uniform thickness 12 . used. Colouring agent COMPRESSED TABLET LOZENGES Colouring agents give colour to the preparation This method is used for preparation of lozenges which makes it more attractive to the peadiatric with heat sensitive active ingredient. The patients. Water soluble and lakolene dyes, FDC granulation method used for preparation of these colour, orange colour , red colour cubes etc, types of lozenges is similar to that used for other are used as colouring agents. compressed tablets. These tablets differ from Flavouring agent conventional tablets in terms of organoleptic Flavouring agents are selected based on the property, non disintegrating characteristics and colouring agent used. Some of the flavouring agents slower dissolution profiles. The compressed tablet used are , eucalyptus oil, spearmint and lozenge is made using heavy compression cherry flavour. equipment to give a harder tablet than usual, since it Whipping agent is required for the troche to dissolve slowly in oral Milk protein, egg albumin, gelatine, xanthan gum, cavity. The preparation of lozenges by tablet starch, pectin, align and carrageenan. compression method is very less common 13 . Humectants Glycerine, propylene glycol and sorbitol. SOFT LOZENGES Soft lozenges are used to prepare a wide variety of TYPES OF LOZENGES drugs. So they are commonly used lozenges. The Lozenges are classified according to site of action, bases usually consist of a mixture of various texture and composition. polyethylene glycols, acacia or similar materials. According to site of action One form of these soft lozenges is the , According to the site of action lozenges are which is defined as a soft variety of lozenge, usually classified as local effect and systemic effect transparent, consisting of a medication in a gelatin, lozenges. Examples of local effect lozenges are glycero-gelatin or acacia: sucrose base. Pastilles are antiseptic, decongestion, etc. Example of systemic easy to use, easy to store at room temperature, effect lozenges are vitamins, nicotine, etc 11 . convenient to carry and are pleasant in taste. If According to Texture and Composition exposed to high temperatures, polyethylene glycol- According to texture and composition lozenges are based lozenges have the tendency to be hygroscopic classified into caramel based medicated lozenges, and may soften 14 . compressed tablet lozenges, soft lozenges and hard candy lozenges. HARD CANDY LOZENGES Hard candy lozenges are solid of sugars. CARAMEL BASED MEDICATED LOZENGES These are mixtures of sugar and other carbohydrates These are also known as chewy lozenges. In this in an amorphous or glassy state. The moisture type the medicament is incorporated into a caramel content and weight of hard candy lozenge should be base which is chewed instead of being dissolved in between, 0.5 to 1.5% and 1.5-4.5g respectively. mouth. These lozenges are especially used for These should not disintegrate and should undergo a pediatric patients and are a very effective means of slow and uniform dissolution over 5-10min. Since administering medications for gastrointestinal hard candy lozenges require high temperature for Available online: www.uptodateresearchpublication.com March – April 85

Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89. their preparation heat labile materials cannot be candy mass is removed from the cooker and incorporated in them. These pastilles were prepared transferred to a lubricated transfer container by heating and congealing method 15 . mounted onto a weight check scale where the weight of the mass is checked. This is followed by PREPARATION METHODS OF LOZENGES color addition in form of , pastes or color CARAMEL BASED MEDICATED LOZENGES cubes. The mass is then transferred to a water- After cooking the candy base at 95-125 ℃, it is jacketed stainless steel cooling table for mixing and transferred to planetary or sigma blade mixer. The the flavor, drug and ground salvage is added. The mixed mass is allowed to cool to the temperature of mass is either poured in mold or pulled into a ribbon 120 ℃. Then the whipping agent is added below while cooling and then cut to desired length 19 . 105 ℃. The medicaments are incorporated between Evaluation Test for Lozenges 95- 105 ℃. Above 90 ℃ color is dispersed in Quality Control is performed for candy base and humectant and added to the above mass. Flavor and lozenges. seeding crystals and are then added below 85 ℃. For the candy base the evaluation is performed for Candies are formed by rope forming following corn syrup and sugar delivery gears, steam pressure, addition of lubricant above 80 ℃16 . temperature, cooking speed, temperature and Compressed Tablet Lozenges vacuum of candy base cooker 20 . Direct compression and wet granulation method is Moisture Analysis 21 used in the preparation of compressed tablet Moisture analysis of lozenges is performed by lozenges. In direct compression, all the ingredients gravimetric method: In this method 1g of sample is are thoroughly mixed together and then weighed and placed in vacuum oven at 60-70 ℃ for compressed. In wet granulation method, the sugar 12-16 hrs. After specific time interval, the sample is content is milled by mechanical pulverisation to a weighed and moisture content is calculated using fine using 40-80 mesh size. The active the following formula. medicament is then added and thoroughly mixed. Moisture content = initial weight - final weight The blended mass is granulated with sugar or corn Azeotropic Distillation Method syrup and size seperated through 2-8 mesh screens. 10-12g of powdered lozenges is used for this Then it is dried and milled using 10-30 size mesh. method. 150-200ml toluene was added to the Before compression the flavouring agent and powder placed in 500ml flask. The flask was fitted lubricant are added 17 . to a reflux condenser and refluxed for 1-2 hours. Soft Lozenges The collected water gives the amount of water Soft lozenges are prepared using fusion method, in present in sample. Karl fisher titration is carried out which the warm mass is poured into in a plastic – A sample of prepared lozenge is calculated to mould. Mould cavity should be overfilled if PEG is obtain 10-250mg of water which is then titrated used, as PEG's contract as they cool. This is not with Karl Fisher reagent. required in case of chocolate as it does not shrink. They are also prepared by hand rolling method, PHYSICAL AND CHEMICAL TESTING 22 where, they are hand rolled and then cut into Hardness pieces 18 . The hardness of lozenges is determined by Hard Candy Lozenges Monsanto or Pfizer hardness tester. The candy base is cooked by dissolving desired Diameter and thickness quantity of sugar in one third amount of water in a The diameter and thickness of the lozenges is candy base cooker. This is continued till the determined by using Vernier calipers. temperature rises to 110 ℃. Corn syrup is added and cooked till the temperature reaches 145-156 ℃. The Available online: www.uptodateresearchpublication.com March – April 86

Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89. Drug excipient interaction studies Stability testing of packaged products Drug excipient interaction studies are carried out to The final packs of lozenges are subjected for check whether any interactions take place between stability testing under following conditions: the drug and the excipients. It is determined by • 25 ℃ at 80% RH for 6-12months using Fourier-transform infrared spectroscopy . • 37 ℃ at 80% RH for 3 months Friability • 25 ℃ at 70% RH for 6-12 months Friability is determined by Roche Friabilator Packaging operated at 25rpm for 4min. A complex and multiple packaging are adopted for Weight variation lozenges since they are hygroscopic in nature. The The variation in weight of the lozenges is individual unit is wrapped in polymeric moisture determined by weighing 20 lozenges and barrier material which is then placed in tight or determining the average weight. Individual weight moisture resistant glass, polyvinyl chloride or metal of the lozenges is compared with the average container. It is then over wrapped by aluminum foil weight. or cellophane membrane. In-vitro drug release Storage 24 In-vitro drug release studies is carried out using The storage of lozenges should be done carefully. USP II paddle type dissolution apparatus. They should be stored away from heat. They should Drug Content be kept out of reach of children. They should be Appropriate number of lozenges are crushed and protected from extreme humidity, since they are dissolved in an appropriate solvent and the hygroscopic. Depending upon the storage absorbance of the solution is measured requirements of both, the drug and the base, either spectrophotometrically. room temperature or refrigerator temperature is 23 Microbial Test for Lozenges usually preferred for storage of medicated chewable Microbial test for lozenges is performed to check lozenges. the presence of any bacterial, mold or spore Applications contamination in raw materials, cooling tunnels, Many drugs have been tried and were successfully finished products, machinery, environmental incorporated in lozenges. Generally they belong to conditions and storage drums. Laboratory microbial one of the following categories: Antiseptics, local testing should include the various counts such as anesthetics, antibiotics, antihistaminics, total plate, total coliform, yeast and mold, E. coli, antitussives, analgesics, decongestants and Staphylococcus and Salmonella. demulcents. Stability Testing Stability testing of lozenges is carried out under following conditions- • 1-2months at 60 ℃ • 3-6months at 45 ℃ • 9-12months at 37 ℃ • 36-60months at 25 and 40 ℃

Table No.1: Classification of lozenges According to site of action According to texture and composition 1. Caramel based medicated lozenges 1. Local effect. Ex. Antiseptic, Decongestants 2. Compressed tablet lozenges 2. Systemic effect. Ex. Vitamins, Nicotine 3. Soft lozenges 4. Hard candy lozenges Available online: www.uptodateresearchpublication.com March – April 87

Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89.

Figure No.1: Lozenges

CONCLUSION REFERENCES Lozenges are medicated sweetened candies that 1. Umashankar M S, Dinesh S R, Rini R, have been used for delivery of drugs for centuries. Lakshmi K S. Chewable lozenge formulation The commercial production of lozenges holds a –A Review, International Research Journal great place in the field of pharmaceutical industry. of Pharmacy , 7(4), 2016, 9-16. Lozenges are organoleptically accepted formulation 2. Stephen O, Majekodunmi. A Review on by the pediatric and geadiatric patients. They are the Lozenges, American Journal of and one of the easiest route of drug administration. They Medical Research , 5(2), 2015, 99-104. are easy to prepare and store. Lozenges produce 3. Renuka P, Madhusudan Y. Lozenges both local and systemic effect during Formulation and Evaluation- A Review, administration. They are used to incorporate a wide International Journal of Advances in range of active ingredients. Sweetened and flavored Pharmaceutical Research , 5(5), 2014, 290- lozenges hold a prime place in pharmaceutical 298. market. They are expected to acquire more demand 4. Phaemachud T, Tuntarawongsa S. in pharmaceutical production as innovative dosage Clotrimazole Soft Lozenges Fabricated with form for the potent drugs which seem to be an ideal Melting and Mold Technique, Res J Pharm dosage form. Most of the medicated chewable Biol Chem Sci , 1(4), 2010, 579-586. lozenges are available as OTC products and are 5. Surbhi C. Review on Lozenges for Oral very cheap when compared to other dosage form. Bacterial Infection, International Journal of Lozenges enjoy an important position in pharmacy Pharmacy , 7(1), 2017, 16-22. and will continue to remain so in future. 6. Esimone C O, Okoye F B C, Odimegwu D C, Nworu N S, Oleghe P O, Ejogha P W. In vitro ACKNOWLEDGEMENT antimicrobial evaluation of lozenges The authors wish to express their sincere gratitude containing extracts of Garlic and Ginger, Int J to Department of Pharmaceutics, Sree Krishna Health Res , 3(2), 2010, 105-110. College of Pharmacy and Research Centre, 7. Tania S, Tejasavi M, Suxam, Sunil K, Sonia Parassala, Thiruvananthapuram, Kerala, India for P, Neeraj B. Medicated Lozenges -A Review, providing necessary facilities to carry out this World Journal of Pharmacy and review work. Pharmaceutical sciences , 7(10), 2018, 751- 756. CONFLICT OF INTEREST We declare that we have no conflict of interest. Available online: www.uptodateresearchpublication.com March – April 88

Subash Chandran M. P. et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 8(2), 2019, 83-89. 8. Greey P, Macdonald I B. Penicillin Agar 17. Shivprasad M, Vaibhav J. Development of Pastilles, Can Med Ass Jrnl , 52(4), 1945, 327- Antifungal Lozenges for Treatment of 330. Oropharyngeal Candidiasis, Indo American 9. Minakshi R, Sachin P, Yuvraj P, Monali M, Journal of Pharmaceutical Research, 5(1), Sudesh S. Medicated lozenges as an easy to 2015, 370-386. use dosage form, World Journal of 18. Laxmi B, Swati G, Sravani P, Indira R, Pharmaceutical Research, 7(16), 2018, 305- Shailaja P. Formulation and Evaluation of 322. Domperidone Candy Lozenges, World 10. Suchitra P, Abhay V. Formulation Journal of Pharmacy and Pharmaceutical Development and Evaluation of Antiemetic science , 6(12), 2017, 1167-1175. Lozenges of Ondansetron Hydrochloride, 19. Kini R, Rathnanand M, Kamath D. International Journal of Pharmaceutical Investigating the suitability of isomalt and Research and Bio-science , 3(3), 2014, 365- glucose as sugar substitute in the 372. formulation of salbutamol sulfate hard candy 11. Dasharath P, Rahul P, Hardik S, Chhagan P. lozenges, J Chem Pharm Res , 3(4), 2011, 69- Formulation and Evaluation of 75. Diphenhydramine Hydrochloride Lozenges 20. Bistra Kostova. Development and Evaluation for Treatment of Cough, World Journal of of Novel Lozenges Containing Marshmallow Pharmacy and Pharmaceutical sciences , 3(5), Root Extract, Pak. J. Pharma. Sci , 26(6), 2014, 822-834. 2013, 1103-1107. 12. Bharkad V B. Formulation and Evaluation of 21. Kesha D, Mitesh K, Ankur T, Ramesh G. Lozenges Tablet of Fluconazole, Indo Formulation Development and Evaluation of American Journal of Pharma Research , 5(1), Herbal Lozenges for the Treatment of 2015, 354-363. Recurrent Aphthous Stomatitis, International 13. Shukla D, Chakraborty S, Mishra B. Journal of Research in Pharmacology and Evaluation of in vivo behavior of controlled Pharmacotherapeutics , 5(4), 2016, 318-325. and pulsatile release pastilles using 22. Binu A, Irene T, Beena P, Eleesey A. pharmacokinetic and γ-scintigraphic Formulation and Evaluation of Herbal techniques , Expert Opin Drug Deliv , 9(11), Lozenges Containing Eucalyptus Oil and 2012, 1333-1345. Coleus Aromaticus Oil, American Journal of 14. Neha D, Aparna C, Prathima S. Formulation Pharmatech Research , 8(1), 2018, 2249- and Evaluation of Medicated Lozenges of 3387. Albendazole for Pediatric use, Asian Journal 23. Hina R, Aqib Z, Zeeshan S, Safila N, Khan U. of Biochemical and Pharmaceutical Polyherbal Extract Based Linkus Lozenges Research , 3(5), 2015, 202-215. for Symptomatic Relief: Design, 15. Kirti S, Sulekha B. Development of Cefixime Development and Evaluation, American Lozenges for Treatment of Throat Infection, Journal of Advance , 5(1), World Journal of Pharmacy and 2017, 011-018. Pharmaceutical Science , 4(7), 2015, 645-656. 24. Chandrashekhar J P, Sujay V R, Medicated 16. Pattanayak D, Das S. Formulation Chewable Lozenges: A Review, Int J Recent development and optimization of medicated Sci Res, 10(04), 2019, 32071-32076. Lozenges for pediatric use, Int J Pharm Sci Res, 3(1), 2012, 138-140. Please cite this article in press as: Subash Chandran M P et al. An overview on medicated chewable lozenges, International Journal of Research in Pharmaceutical and Nano Sciences, 8(2), 2019, 83-89. Available online: www.uptodateresearchpublication.com March – April 89