Page566 Indo American Journal of Pharmaceutical Research, 2014 ISSN NO: 2231-6876 Journal home page: http:///index.php/en/ INDO AMERICAN JOURNAL OF PHARMACEUTICAL RESEARCH A REVIEW ON LOZENGES Satish G Shinde *, Vaishali Kadam, G.R. Kapse, S.B. Jadhav, Md. Zameeruddin, V.B. Bharkad Department of Pharmaceutics, Indira College Of pharmacy, Nanded, Maharashtra India. ARTICLE INFO Article history Received 03/01/2014 Available online 12/01/2014 Keywords Lozenges, direct compression, weight variation. ABSTRACT Lozenges are tablets that dissolve slowly in the mouth and so release the drug in the saliva. Lozenges are used for the local medication dissolving in the mouth or throat, e.g. it will produce local anaesthesia, antiseptic and antibiotic action of drugs. There are different types of lozenges such as Chewable Lozenges, Hard Lozenges, and Soft Lozenges. Chewable lozenges are popular with the paediatric population. Hard-candy lozenges are mixtures of sucrose and other sugars and/or carbohydrates in an amorphous state. Soft lozenges have become popular because of the ease of extemporaneous preparation and applicability to a wide variety of drugs. The lozenges are prepared by direct compression and Wet granulation method. Ordered mixing, Drug adsorption, Drug excipient hybrid mixing by spray drying these are methods by which compressed tablet lozenges are prepared. There are some evaluation parameters by which lozenges will be evaluated such as diameter, weight variation, friability, hardness, In-vitro drug dissolution studies, Stability studies etc. Corresponding author Satish G Shinde S.no.13, At post Dhanegaon, tal-dist.- Nanded-431603, Maharashtra, India 9766708621 satishpharma10@gmail.com Please cite this article in press as Satish G Shinde et al. A review on lozenges. Indo American Journal of Pharm Research.2014:4(01). Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Page567 INTRODUCTION 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. [1] Lozenges are tablets that dissolve slowly in the mouth and so release the drug in the saliva. Lozenges are used for local medication in the mouth or throat, e.g. it will be produce local anaesthesia, antiseptic and antibiotic action of drugs. They can thus be described as slow release tablets for local drug treatment. Disintegrates are not used in the formulation, but otherwise such tablets are similar in composition to conventional tablets. In addition, lozenges are often coloured and include a flavour. The choice of filler and binder is of particular importance in the formulation of lozenges, as these excipients should contribute to a pleasant taste or feeling during tablet Dissolution. The filler and binder used should be water soluble and have a good taste. Common examples of fillers are glucose, sorbitol and mannitol. A common binder in lozenges is gelatin. [2] Lozenges are most often used for localized effects in the mouth. They can also be used for systemic effect if the drug is well absorbed through the buccal lining or is swallowed. [3] Lozenges can be made by molding or by compression at high pressures, often following wet granulation, resulting in a mechanically strong tablet that can dissolve in the mouth. Compressed lozenges (or troches) differ from conventional tablets in that they are nonporous and do not contain disintegrate. As the formulation is designed to release drug slowly in the mouth, it must have a pleasant taste, smoothness, and mouth feel. The choice of binder, filler, colour, and flavour is most important. The binder is particularly important in ensuring retardation of dissolution and pleasant mouth feel. In the lozenges suitable binders including gelatin, guar gum, and acacia gum etc. Sugars such as sucrose, dextrose, and mannitol are preferred to lactose, and xylitol is often included in sugar - free formulations. In order to ensure adequate taste masking and artificial sweeteners including aspartame, saccharin, and sucralose are also included subject to regulatory guidelines. [4] ADVANTAGES 1. Lozenge dosage form is that it is easy to administer to both pediatric and geriatric patients. 2. It has a pleasant taste and will extend the time a quantity of drug remains in the oral cavity to elicit a specific effect. 3. It can be prepared extemporaneously by pharmacists with a minimal amount of equipment and time. 4. Having formulas that are easy to change and can be patient specific. 5. Keeping the drug in contact with the oral cavity for an extended period of time. [6] 6. Improved patient compliance. 7. Rapid onset of action and may offer an improved bioavailability. [7] DISADVANTAGES 1. The lozenge dosage form is that it mistakenly could be used as candy by children. 2. A hard candy lozenge is the high temperature required for their preparation. 3. Hard lozenges become grainy [6] TYPES OF LOZENGES 1. Chewable Lozenges 2. Hard Lozenges 3. Soft Lozenges Chewable Lozenges Chewable lozenges are popular with the paediatric population since they are gummy type lozenges. Most formulations are based on a modified suppository formula consisting of glycerin, gelatin, and water. These lozenges are highly fruit flavoured and may have a slightly acidic taste to cover the acrid taste associated with glycerin. [4] Hard Lozenges Hard-candy lozenges are mixtures of sucrose and other sugars and/or carbohydrates in an amorphous state. They are made from aqueous syrups, the water, which is initially present, evaporates as the syrup is boiled during processing so that the moisture content in the finished product is 0.5% to 1.5%. Because making hard lozenges is similar to candy making, helpful hints can be found by consulting a comprehensive cookbook or a candy-making reference. Flavorings, colours, and special molds can be purchased from some vendors of compounding supplies and from businesses that specialize in selling supplies for making candies and confectionaries. Hard-candy lozenges have become an especially popular compounded dosage form in recent years, and special molds and sucker sticks and wrappers are available from various vendors. [5] Soft Lozenges Soft lozenges have become popular because of the ease of extemporaneous preparation and applicability to a wide variety of drugs. The bases usually consist of a mixture of various polyethylene glycols, acacia or similar materials. One form of these soft lozenges is the pastille, which is defined as a soft variety of lozenge, usually transparent, consisting of a medication in a gelatin, glycerogelatin or Acacia sucrose base. Pastilles may be colored and flavoured and can be either slowly dissolved in the mouth or chewed, depending upon the action desired for the particular incorporated drug. [6]
Page568 MANUFACTURING OF LOZENGES Preparation of compressed tablet lozenges 1. Direct compression- Ingredients can be throughly mixed and directly compressed. 2. Wet granulation- In this sugar is pulverized by mechanical comminution to a fine powder (40-80mesh). Medicament is added and the mass is blended mass. The blended is subjected to granulation with sugar or corn syrup and screened through 2-8mesh screen. This is followed by drying and milling to 10-30mesh size. Flavor and lubricant are then added prior to the compression Compressed tablet lozenges are prepared by developing three different methods under wet granulation technique which includes 1.Ordered mixing: Where drug in finely divided state is made to adhere to the coarser diluents particles by the application of frictional forces. 2.Drug adsorption: Involves the deposition of drug present in the solution on a solid. 3.Drug excipient hybrid mixing by spray drying: where liquid feed is rapidly transformed in to a fine powder. Preparation of compressed tablet lozenges by the method of ordered mixing Ordered mixture was prepared by adding the sieved (80#) Drug in small parts to the weighed amount of Iso-malt and mixed thoroughly for 30 mins. Weighed amounts of other excipients were added to the prepared ordered mixture taken in a mortar and was granulated by wet granulation method using 15%w/v binding agent. The dried granules retained on sieve#44 when passed through sieve#22 together with 15% fines was mixed with weighed amounts of lubricant, glidant and spray dried flavor were compressed in a single punch machine with maximum force to obtain a compact flat faced tablet lozenges. Preparation of compressed tablet lozenges of 10% drug adsorbate Drug adsorbate (10%) was prepared by adding 1 g of drug in boiling water taken in a petri dish with constant stirring on a thermostatically controlled water bath. 10 g of activated magnesium trisilicate (obtained by vacuum drying at 100oC and 720mmHg for 24 hours) was added to the above drug mixture and mixed thoroughly to obtain a homogenous dispersion. Finally the mixture was oven dried at 70oC until the moisture content was less than 1.5%. The sieved free flowing powder was taken along with other excipients in a mortar and was then compressed to lozenges by wet granulation method as explained above. Preparation of compressed tablet lozenges by using spray dried hybrid mixture of base and drug Spray dried hybrid mixture is prepared by separately dissolving weighed quantity of base such as mannitol in distilled water, to which 10%w/w of drug was added with stirring. This homogenous solution is then fed into mini spray drier using a pressure atomizer through Rotating wheel with an atomizing air pressure of 5 kg/sq inch. The inlet temperature (140/160oC), feed pump speed (2/4 ml/min), aspirator level (20/40) and concentrations of mannitol (10%/20%) used were carefully optimized. Weighed quantity of this hybrid mixture was taken along with other excipients (Table 3) in a mortar, and was then compressed to lozenges by wet granulation method as explained above. [8] Preparation of Soft Lozenges Soft lozenges were prepared by melting and mold technique as described previously8. PEG was melted on water bath and mixed with the other ingredients to form a homogeneous mixture. Subsequently, the mixture was poured into the stainless steel mold which size of each mold of tablet was 12 mm diameter and 6.8 mm height as shown in Fig. 1. [10] Figure 1. Stainless steel mold.
Page569 Preparation of hard candy lozenges The various steps involved in preparation of tablet lozenges are Preparation of syrup and maintenance of temp. at 150 0C till it becomes thick. The syrup is then placed in vacuum chamber for about 30 minutes to remove the traces of water molecules and to give plasticity to the base prepared. The drug, mucoadhesive polymers, citric acid, colour and flavorings agents were added manually and mixed thoroughly. Then this solidified mass was placed between the rollers of the batch former to form a rope size and shape. Hot air was blown over the product (Lozenges) in the rotating drying chamber (velocity of 1500-3000 ft/mins as the lozenges passed from the cooling belts). [11] EVALUATION OF PREPARED TABLET LOZENGES The prepared formulations were evaluated for drug content uniformity, tablet hardness, thickness and diameter, weight variation, friability and in vitro disintegration by pharmaceutical standard methods. Diameter The thickness and diameter of lozenges were determined using vernier callipers. Three lozenges from each batch were used and average values were calculated. Weight variation The weight variation was conducted by weighing 20 lozenges individually and calculating the average weight and comparing the individual lozenges weight to the average value. Three lozenges from each batch were selected and weighed individually and crushed in a mortar. Drug was extracted with 100 ml of distilled water. The drug content was determined spectrophotometrically at 276 nm with blank lozenge extract as the reference. Hardness The hardness of the lozenges was determined by using Monsanto Hardness tester, where the force required to break the lozenges was noted. Friability The friability of the lozenges was determined using Roche Friabilator. Weighed lozenges were placed in the friabilator and operated for 4 min at 25 rpm. The tablets were then made free from dust and reweighed. The percentage friability was calculated. Moisture content analysis Moisture content in the final candy is determined by using Helium moisture balance apparatus. The sample was weighed and crushed in a mortar from this one gram of the sample was weighed and the moisture content is determined by the moisture balance apparatus. Mouth dissolving time test The time taken by the candy to dissolve completely was determined by the USP Disintegration apparatus, where hard boiled candy lozenges were placed in each tube of the apparatus and time taken for the lozenges to dissolve completely was noted by using MCIlavine buffer of ph 6.4 at 37oC. In-vitro drug dissolution studies The rate of dissolution possibly is related to the efficacy of the tablet lozenge. Dissolution study was carried out in 800 ml of MCIlavine buffer ph 6.4 by USP II paddle method at 150 rpm. Samples were withdrawn at 5 min interval and replaced immediately with an equal volume of fresh buffer and were analyzed spectrophotometrically at 276 nm. Stability studies The stability studies were performed to assess physical as well as the chemical stability of the drug, which may possibly affect the organoleptic properties of the lozenges. Accelerated stability study was conducted as per ICH guidelines (zone IV) at 45 C and 75% relative humidity over a period of seven weeks. Sufficient number of optimized formulations were packed in amber coloured screw capped bottles and kept in incubator maintained at 37 C. Samples were taken at intervals of 15 days to estimate the drug content and to evaluate organoleptic properties. [9] STORAGE These preparations should be stored away from heat and out of the reach of children. They should be protected from extremes of humidity. Depending on the storage requirement of both the drug and base, either room temperature or refrigerated temperature is usually indicated. PACKAGING Hard candies are hygroscopic and usually prone to absorption of atmospheric moisture. Considerations must include the hygroscopic nature of the candy base, storage conditions of the lozenges, length of time they are stored and the potential for drug interactions. These products should be stored in tight containers to prevent drying. This is especially true of the chewable lozenges that
Page570 may dry out excessively and become difficult to chew. If a disposable mold with a cardboard sleeve is used, it is best to slip this unit into a properly labelled, sealable plastic bag. [6] CONCLUSION Lozenges are most often used for localized effects in the mouth. They can also be used for systemic effect if the drug is well absorbed through the buccal lining or is swallowed. A wide range of actives can be incorporated within their structure. Most of the preparations are available as OTC products and it is easy to administer to both pediatric and geriatric patients. It will be produce local anaesthesia, antiseptic and antibiotic action of drugs. These have been developed about 20th century ago and are still under commercial production. Lozenges enjoy an important position in pharmacy and will continue to remain at the same in future. ACKNOWLEDGEMENT The author is thankful to the management of SSS s Indira college of Pharmacy for providing facilities to utilize library and internet in the college. Special thanks to Miss Kadam madam for their important guidance and Gajanan Kapse for his role as a coauther. REFERENCES 1. Panati, Charles, Panati's Extraordinary Origins of Everyday Things. New York: Harper & Row. ISBN 0060964197, 1989, pp. 258 260. 2. M.E.Aulton, Pharmaceutics the Science Of Dosage Form Design. 2 nd edition p.no. 416. 3. The Pharmaceutics & Compounding Laboratories at the UNC Eshelman School of Pharmacy [http://pharmlabs.unc.edu/labs/lozenge/objectives.htm] 4. Shayne Cox Gad, Pharmaceutical manufacturing handbook Production and Processes, Published by John Wiley & Sons, Inc., Hoboken, New Jersey,2008 p. no. 252-253. 5. Judith E. Thompson and Lawrence W. Davidow, A Practical Guide to Contemporary Pharmacy Practice 3rd edition published by Wolters Kluwer, chapter 26. 6. Loyd V. Allen, Secundum Artem, Troches and Lozenges-Current & Practical Compounding Information for The Pharmacist. Volume 4 Number 2 7. Nirav V. Patel, Sachin Chauhan, Chintan Aundhia, A. K. Seth Indo American Journal of Pharmaceutical Research. 2011:2(1); p.no.146-152. 8. Rajesh Kini, Mahalaxmi Rathnanand. International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304, July-Sept 2011, Vol.3, No.3, p.no. 1375-1381, 9. D Bhowmik, B Chiranjib, Krishnakanth, Pankaj and RM Chandira, Journal of Chemical and Pharmaceutical Research, 2009, 1(1):, p.no. 163-177. 10. Mesnukul A, Yodkhum K, Phaechamud T. Indian Journal of Pharmaceutical Science, 2009; 71: p.no.413-20. 11. Nagoba Shivappa N, PurushothamRao K, Zakaullah S. Journal of Pharmaceutical and Biomedical Sciences, 2011, vol12 (17). Submit your next manuscript to IAJPR and take advantage of: Access Online first Double blind peer review policy No space constraints Rapid publication International recognition Submit your manuscript at: editorinchief@iajpr.com 54878478451001301