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Journal Home Page www.bbbulletin.org BRITISH BIOMEDICAL BULLETIN

Review A REVIEW ON LOZENGES

Rachana Maheshwari, Vikas Jain*, Rehana ansari, S.c. Mahajan, Garvita joshi

Mahakal Institute of Pharmaceutical Studies, India

A R T I C L E I N F O A B S T R A C T

Received 19 July 2013 Received in revised form 24 July 2013 Accepted 10 Aug 2013 Lozenges are solid, unit dosage form of medicament which are meant to be dissolved in mouth or pharynx. Development of lozenges dates back to 20th century and is still in commercial Keywords: Lozenge, production. Most of the lozenge preparations are available as Over Over The Counter medication, The Counter medications. Lozenge provide a palatable means of Troches, dosage form administration and enjoy its position in , Molding. pharmaceutical market owing to its several advantages but it suffers form certain disadvantages too. The dosage form can be adopted for local as well as systemic therapy and a wide range of

actives can be incorporated in them. Lozenges currently available in market are of four types: based soft lozenges, hard lozenges and compressed tablet lozenges. The present

review covers more or less all aspects associated with lozenge. It includes various researches performed till date, formulation and evaluation parameters adopted for the dosage form. Furthermore, Corresponding author: Mahakal Institute of Pharmaceutical Studies, India it throws light on the applications of lozenges. Tel. +91-9617383196 E-mail address: © 2013 British Biomedical Bulletin. All rights reserved [email protected]

Jain et al______ISSN-2347-5447 Introduction The word "Lozenge" is derived from products where there is no need of French word "Losenge" which means a prescription from a medical practitioner diamond shaped geometry having four equal while some are prescribed by the medical sides. Lozenges and pastilles have been practitioners. developed since 20th century in pharmacy and is still under commercial production.1 Advantages Lozenges are solid preparations that  Can be given to those patients who have are intended to dissolve in mouth or difficulty in swallowing.4 pharynx. They may contain one or more  Easy to administer to geriatric and medicaments in a flavored and sweetened pediatric population. base and are intended to treat local irritation  Has a pleasant taste. or infection of mouth or pharynx and may  It extends the time of drug in the oral also be used for systemic drug absorption. cavity to elicit a specific effect. They can deliver drug multi directionally  Easy to prepare, with minimum amount into the oral cavity or to the mucosal of equipment and time.6 2,3 surface.  Do not require water intake for Lozenges are placed in oral cavity. administration. Since the sublingual lozenges may be  Technique is non invasive, as is the case impractical due to their size, buccal lozenges with parenterals. are formulated and have been extensively used and are intended to be placed between Disadvantages the cheek and the gums. Though the lozenge  It could be mistakenly taken as candy dissolution time is about 30 minutes, it also by children, hence should be kept out of depends on the patient, as patient controls the reach of children.6 the rate of dissolution and absorption by  The non ubiquitous distribution of drug sucking on lozenge until it dissolves. The within saliva for local therapy. consequence of this can be high variabilities  Possible draining of drug from oral in amounts of drug delivered each time the cavity to stomach along with saliva. lozenge is administered. Sucking and the subsequent production of saliva may also Medicaments lead to increased dilution of the drug and Drug candidates which can be accidental swallowing.4 incorporated in lozenges, belong to one of Depending on the type of lozenge, the following categories: they may be prepared by molding or by  Antiseptics compression. Molded lozenges are called  Local anesthetics pastilles while compressed lozenges are  Antibiotics 3 called troches.  Antihistaminics Lozenges should dissolve slowly in  Antitussives mouth and possess some degree of  Analgesics smoothness, with their shape being without  Decongestants 5 2 corners. Lozenges may be formulated with  Demulcents. various shapes, like flat, circular, octagonal, biconvex or bacilli, meaning short rods or Classification 2 cylinders.  According to the site of action- Most of the lozenge formulations are available as Over the Counter (OTC)

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 Local effect. Ex. Antiseptics, Manufacturing Decongestants. The candy base is cooked at 95-125oC  Systemic effect. Ex. Vitamins, Nicotine. and transferred to planetary or sigma blade mixer. Mass is allowed to cool to 120oC. This  According to texture and composition- is followed by the addition of whipping agent below 105oC. The medicaments ane then o  Chewy or caramel based medicated added between 95-105 C. Color is dispersed lozenges in humectant and added to the above mass at o  Compressed tablet lozenges a temperature above 90 C. Seeding crystals o  Soft lozenges and are then added below 85 C o  Hard candy lozenges followed by lubricant addition above 80 C. are then formed by rope forming.2 Chewy or Caramel Based Medicated Lozenges Compressed Tablet Lozenges These are the dosage form in which If the active ingredient is heat labile, it medicament is incorporated into a caramel may be made into lozenge preparation by base which is chewed instead of being compression. The granulation is prepared in a dissolved in mouth. manner similar to that used for any Ingredients compressed tablet.2 The lozenge tablets differ  Candy Base- It consist of a mixture of from conventional tablets in terms of and corn in a ratio of 50:50 organolepticity, non-disintegrating to 75:25 sugar to . characteristics and slower dissolution 3  Whipping agent- These are used to profiles. The lozenge is made using heavy incorporate air in -based compression equipment to give a tablet that is confections to obtain the desired degree harder than usual, as it is desirable for the of soft chew. These are exemplified by troche to dissolve slowly in mouth. They are milk protein, egg albumin, gelatin, usually flat faced with sizes, weight, hardness, xanthan gum, starch, pectin, algin and and erosion time ranging between, 5/8-3/4 carageenen. inch, 1.5-4g, 30-50kg inch2 and 5-10min, 2  Humectants- They improv chew and respectively. mouthfeel properties and include Ingredients glycerin, propylene glycol and sorbitol.  Lubricants- These are added to avoid  Tablet base or vehicle- sticking of candy to the teeth while  Sugar- Dextrose, . chewing. It includes vegetable oils and  Sugar-Free vehicles: Mannitol, sorbitol, fats. polyethylene glycol (PEG) 6000 and  Medicaments- Medicaments up to 35- 8000. 40% can be incorporated.  Other fillers- Di calcium phosphate,  Seeding crystals- It involves addition of calcium sulfate, calcium carbonate, fine at 3-10% to warm , microcrystalline cellulose. candy mass to speed up the crystallization and allow the base to be Some commercially available sugar formed into tablets in a much shorter based vehicles include- Emdex, Nu-tab, time. Sweetrex, Mola-tab, Hony-tab, Sugartab.  .  Binders- These are used to hold the particles of mass as discrete granules and

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include acacia, corn syrup, sugar syrup, contract as they cool. This is not required in gelatin, polyvinyl-pyrrolidone, tragacanth case of as it does not shrink.7 and methylcellulose.  Phaechamud and Tuntarawongsa  Lubricants- These are used to improve fabricated clotrimazole soft lozenges by flow of final troche mixture and include molding method and evaluated the magnesium stearate, calcium stearate, factors that affect the physical properties stearic acid and PEG. of lozenge. They found that increasing  Colors- Water soluble and lakolene dyes. amounts of PEG1500, xanthan gum or  Flavors. increased the hardness of the lozenge. And also disintegration time Manufacturing was found to be increased on increasing 8  Direct compression- Ingredients can be amount of actives and hardness. throughly mixed and directly compressed. Hard Candy Lozenges  Wet granulation- In this sugar is pulverized by mechanical comminution Hard candy lozenges are mixtures of to a fine powder (40-80mesh). sugar and other carbohydrates in an Medicament is added and the mass is amorphous (noncrystalline) or glassy state. blended mass. The blended is subjected They can also be regarded as solid of to granulation with sugar or corn syrup . The moisture content and weight of and screened through 2-8mesh screen. hard candy lozenge should be between, 0.5 to This is followed by drying and milling to 1.5% and 1.5-4.5g respectively. These should 10-30mesh size. Flavor and lubricant are undergo a slow and uniform dissolution or then added prior to the compression.2 erosion over 5-10min., and should not disintegrate. The temperature requirements Soft Lozenges for their preparation is usually high hence heat labile materials cannot be incorporated in Soft lozenges are either meant for them.2,6 chewing or for slow dissolution in mouth. They can be made from PEG 1000 or 1450, Ingredients chocolate or sugar-acacia base while some  Bodying agent or base- This includes soft lozenge formulations can also contain Corn syrup which is available on Baume acacia and silica gel. Acacia is used to basis. A 43o Baume corn syrup is provide texture and smoothness to the lozenge preferred in hard candy lozenges. and silica gel is used as a suspending agent to  Sweetening agent- It includes sucrose, avoid settling of materials to the bottom of the dextrose, , lactose. mold cavity during the cooling. The  Acidulents- These are added to candy formulation requires heating process at about base to strengthen the flavor 50oC hence is only suitable to heat resistant characteristics of the finished product. ingredients.6,7 Commonly used acids are citric, tartaric, fumaric and malic acid. Manufacturing  Colors- FD & C colors, orange color On the account of the soft texture of paste, red color cubes, etc. these lozenges, they can be hand rolled and  Flavors- It includes menthol, eucalyptus then cut into pieces or the warm mass can be oil, spearmint, cherry flavor, etc. poured into a plastic mold. Mold cavity should be overfilled if PEG is used, as PEG's

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 Medicaments- Medicaments upto 2-4% retention times were found to be 1hr, can be incorporated in the hard candy <1hr and 4-5hrs, respectively. This lozenges. formulation has already been used in 2  Salvage- Salvage can be liquid or solid. fuso-spirochaetal infection treatment and Manufacturing are being studied for hemolytic The candy base is cooked by streptococcal infection treatment of dissolving desired quantity of sugar in one- throat.11 third amount of water in a candy base cooker.  A multicenter, randomized, double blind, This is continued till the temperature rises to single dose study was carried out by 110oC. Corn syrup is added and cooked till Wade et al., for assessing the efficacy of the temperature reaches 145-156oC. The AMC/DCBA warm and cool lozenge for candy mass is removed from the cooker and the relief of acute sore throat. Analgesic transferred to a lubricated transfer container and sensorial benefits of AMC/DCBA mounted onto a weight check scale where the warm and cool lozenge was compared weight of the mass is checked. This is against unflavored non-medicated followed by color addition in form of placebo lozenge and significant solutions, pastes or color cubes. The mass is analgesic, functional sensorial and then transferred to a water-jacketed stainless emotional effects against the placebo steel cooling table for mixing and the flavor, were observed. Sore throat relief , drug and ground salvage is added. The mass difficulty in swallowing and throat is either poured in mold or pulled into a numbness were observed, also emotional ribbon while cooling and then cut to desired benefits included happiness, better feel length. The obtained lozenges are and less frustration.12 2,6 packaged.  Shukla et al., evaluated in vivo behaviour  Cocaine voice tablet lozenges and of controlled and pulsatile release pastilles were developed in late 1800's pastilles for the treatment of asthma, and were indicated in Extra COPD and for chrono therapeutic Pharmacopoeia, 1888. They were used management of nocturnal asthma. They by singers and public speakers for the found that, enteric coating of pastilles remedy of vocal huskiness and delayed the in vivo drug release and can hoarseness.9 be used in nocturnal asthma.13  Esimone et al., formulated and evaluated antimicrobial activity of herbal lozenge Center Filled Hard Candy Lozenges of garlic and ginger extract by molding These are the hard candy lozenges method. The antimicrobial activity was with soft or liquid centers into their main evaluated against Candida albicans, body. E.coli and Staphylococcus aureus using Nystatin as standard. The formulation inhibited growth of laboratory strains of Quality Control C.albicans but not S.aureus and E.coli General Checks- Candy Base Manufacturing and hence concluded that lozenges can be  As the candy base manufacture is used in non-resistant oral thrush.10 commenced, a check on following  Greey et al., prepared penicillin agar parameters is performed: Corn syrup and pastilles. In order to prolong the retention sugar delivery gears; Temperature, steam time they tried gelatin, gelatin+agar and pressure and cooking speed of precookers agar combinations with penicillin whose and temperature, steam pressure, cooking

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speed and vaccum of candy base factor x 100 cookers.2 Sample weight/250 x Volume of  Moisture analysis- sample solution consumed by Fehling's . Gravimetric method- 1g sample is solution. weighed and placed in vaccum oven = Percent reducing sugar. at 60-70oC for 12-16hrs. Final weight is subtracted from initial and the  Salvage solutions- Solid contents of difference in moisture content is salvage solutions is determined using a calculated. refractometer.2 . Karl Fisher titration- A sample  Forming checks- It involves a check on calculated to contain 10-250mg candy rope diameter.2 water is taken in titration flask and  Cooling checks- Visual inspection is titrated with Karl Fischer reagent. performed in order to analyze any stress . Azeotropic distillation method- 10- cracking due to rapid cooling, air bubble 12g candy is pulverized and placed formation, surface cracking and black in 500ml flask to which 150-200ml specks.2 toluene is added. Flask is connected  Physical and Chemical Testing- to a reflux condenser and is refluxed . Hardness- This is determined by for 1-2hrs. Water collected gives the Pfizer or Monsanto hardness amount of water present in the tester.14,15 sample.2 . Diameter and thickness- This is  Determination of sugar and corn syrup determined by vernier calipers. ratios- . Drug excipient interaction studies- This is performed by "Dextrose Determined by FTIR.14 equivalent method: Lane Eynon Titration . Friability - Determined by Roche method".2 Friabilator operated at 25rpm for  Percentage reducing sugars- 4min. Standard- 3g anhydrous dextrose is . Weight variation- 20 lozenges are dissolved in 500ml water. The solution is weighed and average weight is boiled for 2min and 2 drops of methylene determined. Individual weight is blue is added and titrated against 25ml of compared to the average weight. alkaline cupric tartrate solution (Fehling's . In-vitro drug release- This is carried solution) to a yellowish red end point.2 out in USP II paddle type dissolution apparatus.15 (3g) x (volume of standard dextrose solution . Drug content- Appropriate number Consumed by Fehling's solution) of lozenges are crushed and 500 dissolved in an appropriate solvent = reducing sugar factor for 3g dextrose and the absorbance of the solution is measured spectrophotometrically. Sample- 10g sample of candy base is  Microbial Check dissolved in 250ml of water and titrated with In this, the presence of any bacterial, 25 ml of Fehling's solution in the same mold or spore contamination is checked in manner as the standard. raw materials, finished products, machinery, cooling tunnels, environmental conditions and storage drums. Laboratory microbial testing should include the following counts:

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 Total plate A variety of drug candidates can be  Total coliform incorporated in them for the treatment of and  Yeast and mold relief from conditions of oral as well as throat  E.coli infections such as oral thrush, sore throat,  Staphyllococcus cough, gingivitis, pharyngitis, decongestant, 2  Salmonella. etc. Moreover these also have been used to  Stability Testing deliver the drug systemically for smoking  Stability testing of product- Lozenges are cessation and pain relief. subjected to stability testing under following conditions- Conclusion 1-2months at 60oC 3-6months at 45oC Lozenges are medicated confections 9-12months at 37oC designed for local as well as systemic therapy. 36-60months at 25 and 4oC.2 A wide range of actives can be incorporated  Stability testing of product in package- within their structure. Most of the Lozenges in their final packs are preparations are available as OTC products and are very economic dosage forms. These subjected to following conditions for th stability testing: have been developed about 20 century ago 25oC at 80%RH for 6-12months and are still under commercial production. 37oCat 80%RH for 3 months Lozenges enjoy an important position in 25oC at 70%RH for 6-12 months.2 pharmacy and will continue to remain at the same in future. Packaging Authors' Contributions Since the lozenges are hygroscopic in nature a complex and multiple packaging is Rachana Maheshwari has contributed adopted. The individual unit is wrapped in to the acquirement of data and drafting of the polymeric moisture barrier material which are manuscript. then placed in tight or moisture resistant glass, Rehana Ansari has contributed in data polyvinyl chloride or metal container that is acquisition. Dr. Vikas Jain has guided as well over wrapped by aluminum foil or cellophane as reviewed and approved the version to be membrane.3 published. Dr. S.C. Mahajan and Mrs. Garvita Joshi have reviewed and approved the article Storage for publication.

Lozenges should be stored away from Acknowledgement heat and out of reach of children. They should be protected from extremes of humidity. I would like to extend my gratitude Depending upon the storage requirements of towards my guide and our Head of both, the drug and the base, either room Department, Dr. Vikas Jain and our Director temperature or refrigerator temperature is of college, Dr. S.C. Mahajan who guided me usually indicated.2 and provided me moral support throughout the preparation of manuscript. I would also like to thank my family, brother and my Applications colleagues who provided me their full support for the same. Lozenges are employed for the treatment of local as well systemic disorders.

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References 9. Developing Treatments with Controlled Drugs. Part One: Cannabis, Coca, and 1. Lozenges and Pastilles, Prolonged Cocaine. Museum of the Royal Medication From Palatable Preparations. Pharmaceutical Society. 2011. Royal Pharmaceutical Society, Information 10. Esimone CO, Okoye FBC, Odimegwu DC, sheet: 4. Nworu CS, Oleghe PO, Ejogha PW. In vitro 2. Peters d. Medicated Lozenges. In: Lieberman Antimicrobial Evaluation of Lozenges HA, Lachman L, Schwartz JB, editors. Containing Extract of Garlic and Ginger. Int Pharmaceutical Dosage Forms: Tablets. 2nd J Health Res. 2010; 3(2): 105-110. ed. New York: Marcel Dekker, Inc.; 2005. p. 11. Greey P, Macdonald IB. Penicillin Agar 419-577. Pastilles. CMAJ. 1945; 52(4): 327-330. 3. Mendes RW, Bhargava H. Lozenges. In: 12. Wade AG, Morris C, Shephard A, Crawford Swarbick J, editor. Encyclopedia of GM, Goulder MA. A multicenter Pharmaceutical Technology. 3rd ed. North randomized, double blind, single-dose study California, USA: Informa Healthcare Inc.; assessing the efficacy of AMC/DCBA Warm 2006. p. 2231-2235. lozenge or AMC/DCBA Cool lozenge in the 4. Batheja P, Thakur R, Michniak B. Basic relief of acute sore throat. BMC Fam Pract. Biopharmaceutics of Buccal & Sublingual 2011; 12(6). Absorption. In: Touitou E, Barry BW, 13. Shukla D, Chakraborty S, Mishra B. editors. Enhancement in drug delivery. Evaluation of in vivo behaviour of controlled London, New York: CRC Press, Taylor and and pulsatile release pastilles using Francis Group; 2006. p. 189. pharmacokinetic and γ-scintigraphic 5. James MD. Medicated Lozenges. Br Med J. techniques. Expert Opin Drug Deliv. 2012; 1880; 880. 9(11): 1333-1345. 6. Allen LV. Troches and Lozenges. Secundum 14. Pattanayak D, Das S. Formulation Artem. Current & Practical Compounding Development and Optimization of Information for the Pharmacist. 4(2). Medicated Lozenges For Pediatric Use. Int J 7. Lozenges and medication sticks. The Pharm Sci Res. 2012; 3(1):138-140. Pharmaceutics and compounding 15. Kini R, Rathnanand M, Kamath D. Laboratory. UNC ESHEL MAN/school of Investigating the suitability of and pharmacy. liquid as in the 8. Phaemachud T, Tuntarawongsa S. formulation of Salbutamol sufate hard candy Clotrimazol Soft Lozenges Fabricated with lozenge. J Chem Pharm Res. 2011; 3(4): 69- Melting and Mold Technique. Res J Pharm 75. Biol Chem Sci. 2010; 1(4): 579-586. 16. Michaud J. Pharmaceutical Confectionary. PharmaChem. Pharmaceuticals. 2002; 24-27.

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Table 1. Types of center filled lozenges2 Type of center Fill Weight Shelf life S.no. Composition filled lozenge (%) (months) Fruit juice, sugar syrup, hydroalcoholic solutions or 1 Liquid fill 10-20 6-9 sorbitol solution. Jams and jellies whose viscosity has been modified 2 Fruit center 20-25 12-15 with corn syrup or liquid sucrose 3 Paste center Granules and crystals formulated as paste 40 24 Medicament or flavor being suspended or 4 Fat center 25-32 36-60 dissolved in hydrogenated vegetable oil Table 1 provides a concise description on the types of center fills in hard candy lozenges.

Table 2. Applications of hard candy lozenges16

Active Ingredient Applications Amylmetacresol Throat infection Phenol Throat infection Benzocaine Mouth and throat infection Camphor Sore throat relief Hexyl resorcinol Sore throat relief Cetyl pyridinium chloride Pharyngitis Diphenhydramine Cough suppressant Cough and sore throat relief Menthol Decongestant Table 2 provides a list of some of the drugs which can be incorporated in lozenge and their area of applications.

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