Volume 11, Issue 1, November December 2011; Article-017

ISSN 0976 044X

Review Article MOUTH DISSOLVING TABLETS: AS A POTENTIAL DRUG DELIVERY SYSTEM - A REVIEW
Sonia Dhiman*, Thakur Gurjeet Singh, Dharmila and Pravin Pawar Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, India.

Accepted on: 26-07-2011; Finalized on: 30-10-2011. ABSTRACT In the present scenario, there is an ever increasing demand for more patient compliant dosage forms. One of an important innovation in this direction is the development of mouth dissolving tablets that dissolve or disintegrate instantly upon contact with recipients tongue or buccal mucosa. They have proved to be ideal for geriatric and pediatric population, people suffering from dysphagia, clinical conditions where water intake is not available and for drugs undergoing high first pass metabolism. Mouth dissolving tablets (MDT) are the one which suit the concept of better patient compliance, rapid absorption, rapid onset of action, more efficacy, enough bioavailability to show required pharmacological action and less toxicity. It is found that about 26% of patients experience difficulty to swallow the solid dosage forms like tablets and capsules etc. MDTs show rapid disintegration or dissolution in no time through various mechanisms when placed over the tongue without the need of water and overcome the disadvantages of conventional solid dosage forms. Mouth dissolving drug delivery systems have started gaining popularity and acceptance as new drug delivery systems which aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. The aim of this review is to describe the past and the present of mouth dissolving tablet dosage form. Keywords: Mouth dissolving tablets, Buccal mucosa, First pass metabolism, Patient compliance.

INTRODUCTION Oral drug delivery is the most desirable and preferred method of administering therapeutic agents for their systemic effects. In addition, the oral medication is generally considered as the first avenue investigated in the discovery and development of new drug entities and pharmaceutical formulations, mainly because of its manifold advantages it provides to the patients like ease of ingestion, avoidance of pain, versatility, accurate dosing, cost effective and most importantly the patient compliance1. Of drugs that are administered orally, solid oral dosage forms represent the preferred class of product. The reason for this preference are that, the tablets and capsules represent unit dosage forms in which one usual dose of the drug has been accurately placed. By comparison, liquid oral dosage forms, such as syrups, suspensions, emulsions, solutions, and elixirs, suffer from the drawbacks of inaccuracy of dosage and inconvenience of transportation and handling2. Although tablets and capsules are the most popular solid dosage forms but evident drawback of this dosage forms for some patients, is the difficulty to swallow. This difficulty in swallowing or dysphagia is currently affecting approximately 55% of the 3 general population . Drinking water plays an important role in the swallowing of oral dosage forms. Often times people experience inconvenience in swallowing conventional dosage forms such as tablet when water is not available, in the case of the motion sickness (kinetosis) and sudden episodes of coughing during the common cold, allergic condition and bronchitis. For these reason, tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention4.

Such types of tablets are known as mouth dissolving tablets (MDT). These dosage forms rapidly disintegrate and/or dissolve to release the drug as soon as they come in contact with saliva, thus obviating the need for water during administration. The faster the drug into solution, quicker the absorption and onset of clinical effect. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablets dosage form5. Mouth dissolving tablets (MDT) are also called as orally disintegrating tablets, orodispersible tablets, quick disintegrating tablets, fast disintegrating tablets, fast dissolving tablets, rapid dissolving tablets, immediate release tablets, porous tablets, and rapimelts. United States Food and Drug Administration (FDA) defined MDT as "A solid dosage form containing medicinal substance or active ingredient which disintegrates rapidly usually within a matter of seconds when placed upon the tongue." The disintegration time for MDTs generally ranges from several seconds to about a minute. Recently, European Pharmacopoeia has used the term Orodispersible tablet for tablets that disperses readily and within 3 min in mouth before swallowing. Mouth dissolving tablets are designed to disintegrate and release their medication with no special rate controlling features, such as special coatings and other techniques. Tablets of this type are designed for children and the elderly or for 6 any patient who has difficulty in swallowing tablets . The target populations for these new mouth dissolving/disintegrating dosage forms have generally Page 85

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Volume 11, Issue 1, November December 2011; Article-017 been pediatric, geriatric, and bedridden or developmentally disabled patients. Patients with persistent nausea, who are travelling, or who have little or no access to water are also good candidates for mouth 7 dissolving tablets . Elderly patients may find the administration of the conventional oral dosage forms difficult as they regularly require medicines to maintain a healthy life. Children may also have difficulty in ingesting because of their underdeveloped muscular and nervous systems. It has been reported that in case of Dysphagia (difficulty in swallowing), which is common among all age groups and in some cases like motion sickness, sudden episodes of allergic attacks or coughing and unavailability of water, swallowing conventional tablets also become difficult. Hence they do not comply with prescription, which results in high incidence of non-compliance and ineffective therapy8. A survey of 6158 GP patients conducted in Norway indicated that approximately 26% of all patients do not take their prescribed medication as they encountered problems when swallowing conventional tablets. The main complaints often dealt with the size, surface and taste of the tablets. Oral mouth dissolving tablets help overcome some of these problems: the rapid disintegration of the tablet into a solution (containing the drug) enables those who find difficulty in, or experience discomfort when swallowing, to have a more patient friendly experience9. Mouth dissolving drug delivery systems have started gaining popularity and acceptance as new drug delivery systems which aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. Drug Delivery to the Oral Cavity Drug delivery via oral cavity is promising owing to ease of administration and a rich supply of blood and lymphatic vessels. In addition, this route offers high permeability to drugs and good reproducibility. Drugs absorbed via the buccal mucosa enter the systemic circulation directly through the jugular vein. This ensures a rapid onset of action and avoids first- pass liver metabolism, gastric acid 10 hydrolysis, and intestinal enzymatic degradation . Of the range of pharmaceutical preparations available for administration into the oral cavity, the most popular form is that of a mouth dissolving tablet that releases its drug contents for absorption across the oral mucosa. Various parts of oral cavity are shown in Fig.1.

ISSN 0976 044X afterwards, travelling through the many branch arteries and capillaries, returns to the systemic circulation via the jugular veins. The presence of saliva in the mouth is important to drug absorption for two main reasons: 1. Drug permeation across moist (mucous) membranes occurs much more readily than across nonmucous membranes. 2. Drugs are commonly administered to the mouth in the clinical setting in a solid form. The drug must, therefore, first dissolve in saliva before it can be absorbed across the oral mucosa; that is, the drug cannot be absorbed directly from a tablet. Advantages of Mouth Dissolving Tablets
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i) Rapid disintegration of tablet results in quick dissolution and rapid absorption which provide rapid onset of action. ii) Allows high drug loading. iii) Alternative to liquid dosage form. iv) Formulation is cleared from the esophagus especially in the supine position without lodging or sticking to it when swallowed, thus offering improved safety. v) Cost effective. vi) No risk of choking vii) New business opportunities; line extension, exclusively of product promotion and patent life extension. Characteristics of Ideal Mouth Dissolving Tablets12 i) They should not require water for administration yet dissolve or disintegrate in the mouth within a few seconds. ii) They should have pleasing mouth feel. iii) They should leave minimal or no residue in the mouth after oral administration. iv) They should allow high drug loading. v) They should be compatible with taste masking agents and other excipients. vi) They should exhibit low sensitivity to environmental conditions like humidity and temperature. vii) They should have sufficient mechanical strength to withstand the vigorous of the manufacturing process and post manufacturing handling. viii) They should be adaptable and amenable to existing processing and packaging machinery.
VARIOUS TECHNIQUES FOR MOUTH DISSOLVING TABLETS

The mouth dissolving property of the tablet is attributable to a quick ingress of water into the tablet matrix resulting in its rapid disintegration. Hence, the basic approaches to develop mouth dissolving tablets include maximizing the porous structure of the tablet matrix, incorporating the appropriate disintegrating agent, and using highly watersoluble excipients in the formulation. 1) Freeze drying technology: Lyophilization can be used to prepare tablets that have very porous open matrix network into which saliva rapidly moves to disintegrate lyophilized mass after it is placed in mouth. The drug is entrapped in a water soluble matrix which is freeze dried to produce a unit which rapidly disperses when placed in mouth. The preferred drug characteristics for freeze drying formulations are water insoluble, low dose, chemically stable, small particle size and tasteless. Lyophilization is relatively expensive and time consuming Page 86

Figure 1: Various parts of mouth (oral cavity) Blood is richly supplied to the salivary glands and their ducts by branches of the external carotid artery and

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Volume 11, Issue 1, November December 2011; Article-017 manufacturing process. Other drawback includes fragility, which make the use of conventional packing difficult and poor stability during storage under stressful condition12,13. 2) Tablet moulding technology: Moulded tablets are designed to facilitate fast absorption of drugs through the mucosal lining of mouth by inclusion of water-soluble ingredients. The advantage of this system is that it has a porous structure which enhances dissolution (thereby enhanced bioavailability) and decreased first pass metabolism of certain drugs. As moulding process is employed usually with soluble ingredient (saccharides) which offers improved mouth feel and disintegration of tablets. However, moulded tablets have low mechanical strength, which results in erosion and breakage during handling. Different moulding techniques can be used to prepare mouth dissolving tablets: a. Compression moulding: The powder mixture previously wetted with a solvent like ethanol/water is compressed into mould plates to form a wetted mass. b. Heat moulding: A molten matrix in which drug is dissolved or dispersed can be directly moulded into orodispersable tablets. c. No vacuum lyophilization: This process involves evaporation of solvent from a drug solution or suspension at a standard pressure14. 3) Spray drying technology: Spray drying is used in pharmaceutical industries to produce highly porous powders. The processing solvent is evaporated rapidly by spray drying, which renders the product highly porous and thus can be used in manufacturing mouth dissolving tablets. Tablets manufactured from the spray-dried powder have been reported to disintegrate in less than 20 seconds in aqueous medium15, 16. 4) Direct compression method: Direct compression is a process by which tablets are compressed directly from mixtures of the drug and excipients, without any preliminary treatment17. It offers advantages over the other manufacturing processes for tablets, such as wet granulation and provides high efficiency. The mixture to be compressed must have adequate flow properties and cohere under pressure thus making pretreatment as wet granulation unnecessary. In many cases, the superdisintegrants have a major role in the disintegration and dissolution process of mouth dissolving tablets made by direct compression. The choice of a suitable type and an optimal amount of disintegrants is paramount for ensuring a high disintegration rate. The addition of other formulation components such as water soluble excipients or effervescent agents can further enhance dissolution or disintegration properties18. The disintegrant addition technology (direct compression) is the most preferred technique to manufacture the tablets due to certain advantages:

ISSN 0976 044X a. High doses can be accommodated and final weight of the tablet can exceed that of other methods. b. Easiest way to manufacture the tablets. c. Conventional equipment and commonly available excipients are used d. A limited number of processing steps are involved. e. Cost-effectiveness. Tablet size and hardness strongly affect the disintegrant efficacy. Hard and large tablets have more disintegration time than normally required. Very soft and small tablets have low mechanical strength. So, an optimum kind and concentration of disintegrant should be chosen to achieve 18,19 quick disintegration and high dissolution rates . 5) Sublimation technology: The key to rapid disintegration for mouth dissolving tablets is the presence of a porous structure in the tablet matrix. Conventional compressed tablets that contain highly water-soluble ingredients often fail to dissolve rapidly because of low porosity of the matrix. Hence, to generate porous matrix, volatile ingredients are used that are later subjected to a process of sublimation20. Sublimation is a process in which water passes directly from solid state to vapour state without passing through liquid state. This process involves addition of some inert volatile substances like urea, urethane, naphthalene, camphor, etc to other excipients and the compression of blend into tablet. Removal of volatile material by sublimation creates pores in tablet structure, due to which tablet dissolves when comes in contact with saliva. Additionally several solvents like cyclohexane, benzene etc can also be used as pore forming agents21. Various steps involved in sublimation technique for preparation of MDT are shown in Fig. 2.

Figure 2: Schematic view of the preparation of a porous tablet using sublimation of camphor 6) Mass-extrusion technology: This technology involves softening the active blend using the solvent mixture of water soluble polyethylene glycol using methanol and expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets. The dried cylinder can also be used to coat granules of bitter tasting 22 drugs and thereby masking their bitter taste . 7) Melt granulation technology: Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time Page 87

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Volume 11, Issue 1, November December 2011; Article-017 consuming and uses less energy than wet granulation. It is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as griseofulvin23. This approach to prepare MDT with sufficient mechanical integrity, involves the use of a hydrophilic waxy binder (Superpolystate, PEG-6-stearate)24. 8) Phase transition process: MDTs were produced by compressing powder containing erythritol (melting point: 122C) and xylitol (melting point: 93-95C), and then heating at about 93C for 15 min(as shown in Fig.3) After heating, the median pore size of the tablets was increased and tablet hardness was also increased. The increase of tablet hardness with heating and storage did not depend on the crystal state of the lower melting point sugar alcohol25.

ISSN 0976 044X product that is both pleasing to the eye and also to the senses of taste and touch. Disadvantages i) Process is expensive and time consuming. ii) Zydis tablets are light weight and fragile, thus unsuitable for conventional blister packaging. iii) The Zydis formulation has poor stability at higher temperatures and humidities. If there is any pinhole or minor damage to the package, the patient may find the lyophilized product has collapsed 28 due to absorption of moisture . 2) Orasolv Technology: OraSolv is Cima's first fastdissolving/disintegrating dosage form. The OraSolv technology, unlike Zydis, disperses in the saliva with the aid of almost imperceptible effervescence. Orasolv technology is an oral dosage form that combines tastemasked drug ingredients with an effervescent excipient system and requires conventional manufacturing process and equipment. The OraSolv technology is utilized in more than eight marketed products: four Triaminic Softchew formulations, Tempra FirsTabs, and Remeron SolTab. Advantages i) Orasolv dosage forms have been developed containing >1000mg of active load and are capable of combining multiple active ingredients in a tablet. ii) Low degree of compaction used in orasolv avoids the fracture of the particle coating being used for taste-masking. Lyophilization and high degree of compaction (used in other techniques) may disrupt such a taste-masking approach. Disadvantages i) The tablets are very soft and friable. ii) The Orasolv tablets take 15-60 seconds to dissolve in the mouth, which is longer than fast melting oral dosage forms29. 3) Durasolv Technology: DuraSolv is Cima's secondgeneration mouth-dissolving/disintegrating. In this technology active ingredient is mixed into a matrix containing non-direct compression filler, a relatively high lubricant content and a wicking agent and then compressed into tablets. Durasolv is an appropriate technology for products requiring low amounts of active ingredients. DuraSolv is currently available in more than four products. Advantages i) DuraSolv has much higher mechanical strength than Orasolv, due to the use of higher compaction pressures during tableting. The DuraSolv product is thus produced in a faster and more cost-effective manner. ii) DuraSolv is so durable that it can be packaged in either traditional blister packaging or vials. Disadvantages i) The technology is not compatible with larger doses of active ingredients, because the formulation is subjected Page 88

Figure 3: Schematic illustration of a mouth dissolving tablet prepared by the phase transition method using a higher melting sugar alcohol and a lower melting sugar alcohol. 9) Cotton Candy Process: The cotton candy process is also known as the candy floss process and forms the basis of the technologies such as Flash Dose (Fuisz Technology). An MDT is formed using a candyfloss or shear form matrix; the matrix is formed from saccharides or polysaccharides processed into amorphous floss by a simultaneous action of flash melting and centrifugal force. The matrix is then cured or partially recrystallised to provide a compound with good flow properties and compressibility. The candyfloss can then be milled and blended with active ingredients and other excipients and subsequently compressed into ODT. However the high processing temperature limits the use of this technology to thermostable compounds only26. DIFFERENT PATENTED TECHNOLOGIES 1) Zydis Technology: Zydis, the best known of the mouthdissolving/disintegrating tablet preparations, was the first marketed new technology tablet. Tablet is prepared by lyophilization of the drug in a matrix of water soluble carrier (eg. Gelatin). The tablet dissolves in the mouth 27 within seconds after placement on the tongue . More than twenty products are currently available using Zydis technology. In the U.S., they include: Claritin Reditab, Dimetapp Quick Dissolve, Feldene Melt, Maxalt-MLT, Pepcid RPD, Zofran ODT and Zyprexa Zydis. Advantages i) The Zydis product is made to dissolve on the tongue in 2 to 3 seconds. ii) The Zydis formulation is self-preserving because the final water concentration in the freeze-dried product is too low to allow for microbial growth. iii) The combination of lyophilization and taste masking creates a

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Volume 11, Issue 1, November December 2011; Article-017 to high compaction pressure. The structural integrity of any taste masking may be compromised with high drug doses. The drug powder coating in DuraSolv may become fractured during compaction, exposing the bitter-tasting drug to a patient's taste buds. Therefore, the DuraSolv technology is best suited for formulations including relatively small doses of active compound30. 4) Wowtab Technology: The Wowtab fastdissolving/disintegrating tablet formulation has been on the Japanese market for a number of years. The Wowtab technology utilizes sugar and sugar-like (e.g., mannitol) excipients, which display high aqueous solubility and sweetness and hence, imparts taste masking and a pleasing mouth feel31. Mizumoto. et al., have classified sugar-based excipients into two types based on their 32 mouldability and dissolution rate . Type I Saccharides: lactose and mannitol exhibit low mouldability and a high dissolution rate. Type II Saccharides: maltose and maltitol exhibit high mouldability and low dissolution rate. The two different types of saccharides are combined to obtain a tablet formulation with adequate hardness and fast dissolution rate32, 33. The Wowtab product dissolves quickly in 15 seconds or less. Advantages i) Sufficient hardness to maintain the physical characteristics of the dosage form during production until it comes in contact with moisture such as saliva in mouth. ii) More stable to the environment than Zydis or Orasolv product due to its significant hardness. iii) Suitable for both conventional bottle and blister packaging. iv) The taste-masking technology utilised in Wowtab offers a superior mouthfeel due to the patented smoothmelt action. v) High dissolution rate and high mouldability due to two types of saccharides used. Disadvantages It cannot be used in patients of diabetes and other sugar related problems34. 5) Flashdose Technology: Flashdose utilizes a unique spinning mechanism to produce a floss-like crystalline structure, much like cotton candy. This crystalline sugar can then incorporate the active drug and be compressed into a tablet. This procedure has been patented by Fuisz and is known as Shearform. Instead of a floss-like material, small spheres of saccharides can be produced to carry the drug. The process of making microspheres has been patented by Fuisz, and is known as Ceform and serves as an alternative method of taste masking35. 6) Flash Tab Technology: It is a rapid method to produce the disintegrable multiparticulate tablet. The ingredient mixture is suitable for imparting a faster disintegration rate in the mouth (< 60 seconds), due to the presence of active substance in the form of coated microcrystals or

ISSN 0976 044X uncoated microgranules. Coated multiparticles of active ingredients have the advantage of taste masking. These may be prepared by using conventional techniques like coacervation, microencapsulation, and extrusionspheronisation. Advantages i) Conventional tableting techniques are used. ii) The produced tablets have high mechanical strength. iii) Taste- masking is effectively done by coating the 36 microcrystals . 7) Quicksolv Technology: This technology is patented by Janssen Pharmaceuticals. It utilizes two solvents in formulating a matrix, which disintegrates instantly. Methodology includes dissolving matrix components in water and the solution or dispersion is frozen. Then dry the matrix by removing water using an excess of alcohol (solvent extraction). Thus the product formed has 37 uniform porosity and adequate strength for handling . 8) Lyoc Technology: Lyoc technology is patented by pharmalyoc. Oil in water emulsion is prepared and placed directly into blister cavities followed by freeze-drying. Nonhomogeneity during freeze-drying is avoided by incorporating inert filler to increase the viscosity finally the sedimentation. High proportion of filler reduces porosity of tablets due to which disintegration is lowered38. 9) Ziplets Technology: Recently Eurand (Pessano con Bornago, Italy) developed the Ziplets technology, which can be used with water insoluble compounds as both bulk actives and as coated microparticles (the latter containing soluble and/or insoluble drugs). In fact, tablets composed primarily of water-soluble components often tend to dissolve rather than disintegrate, resulting in a much longer disintegration time. As the soluble components dissolve on the tablets outer layer, the rate of the water diffusion into the tablet core decreases because of the formation of concentrated viscous solutions39. 10) Oraquick Technology: The Oraquick fastdissolving/disintegrating tablet formulation utilizes a patented taste masking technology. The taste masking process does not utilize solvents of any kind, and therefore leads to faster and more efficient production. Also, lower heat of production than alternative fastdissolving/disintegrating technologies makes Oraquick appropriate for heat-sensitive drugs. Oraquick claims quick dissolution in a matter of seconds, with good tastemasking. There are no products using the Oraquick technology currently on the market, but KV Pharmaceutical has products in development such as analgesics, scheduled drugs, cough and cold, 40 psychotropics, and anti-infectives . Various patented technologies with their company name and the list of active ingredients manufactured by them are listed here under in Table 1.

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Volume 11, Issue 1, November December 2011; Article-017 Table 1: List of various Patented technologies with their Company and Product Name
S. No. 1 2 3 4 5 6 7 8 9 10 11 Patented Technology Zydis Orasolv Durasolv Wowtab Flashdose Flashtab Quicksolv Lyoc Ziplets Oraquick Advatab Basis of Technology Lyophilization Direct compression Direct compression Direct compression Cotton Candy Process Direct compression Lyophilization Lyophilization Direct compression Micromask taste masking Microcaps and diffuscap CR Technology Technology developed by Company R.P.Scherer, Inc Cima Labs, Inc. Cima Labs, Inc. Yamanouchi Pharma Tech. Inc. Fuisz Technology. Ltd. Ethypharm Janssen pharmaceutics Farmalyoc Eurand International KV Pharm.Co.,Inc. Eurand International

ISSN 0976 044X

Active Ingredient (Brand Names) Loratidine (Claritin Reditab and Dimetapp Quick Dissolve). Paracetamol (Tempra Quicklets), Zolmitriptan (Zolmig Repimelt). Hyoscyamine Sulfate (NuLev) Zolmitriptan (Zolmig ZMT) Famotidine (Gaster D) Tramadol HCl (Relivia Flash dose) Ibuprofen (Nurofen FlashTab) Cisapride monohydrate (Propulsid Quicksolv), Risperidone (Risperdal MTab) Phloroglucinol Hydrate(Spasfon Lyoc) Ibuprofen (Cibalgina DueFast) Hyoscyamine Sulfate ODT AdvaTab cetrizine, AdvaTab Paracetamol

Reported Advances in Mouth Dissolving Tablet Dosage Forms: Table 2: Recently used drugs along with super disintegrant added and method adopted for preparation of mouth dissolving tablet dosage form.
SUPERDISINTEGRANT METHODS REFERENCES Kolliodon CL, Explotab, Camphor, Citric Direct Compression, 43 Acid, Ammonium Bicarbonate, Sublimation Method, Sodium Bicarbonate, Effervescent Method. 2 Oxcarbazepine Polyplasdone XL10 Primojel, Direct Compression 44 Ac-Di-Sol 3 Aceclofenac CP, CCS, SSG Direct compression 45 4 Felodipine CP, SSG Direct Compression 46 5 Losartan Potassium Polyplasdone XL 10, CCS, Explotab Direct Compression 47 6 Carbamazepine CCS, CP, SSG Direct Compression 48 7 Domperidone Camphor, CP Sublimation method 49 8 Celecoxib SSG Holt Melt Extrusion, Direct Compression 50 9 Amlodipine Besylate Ac-Di-Sol, SSG, Kollidon-CL Sublimation Method 51 Camphor 10 Lornoxicam KYRON T-314 (Polacrillin Potassium), Wet Granulation Technique 52 Menthol 11 Nimesulide CCS, CP Direct Compression 53 12 Promethazine HCL SSG, CP,CCS, Pregelatinised Starch Direct Compression 54 13 Salbutamol Sulphate Primojel, Kollidon-CL, L-HPC Direct Compression 55 14 Tramadol HCl SSG, D-mannitol Extrusion/ Spheronization Process 56 15 Cinnarizine CP,CCS, L-HPC Sublimation Method 57 16 Rosiglitazone SSG, CP, CCS Direct Compression 58 17 Meloxicam CP, SSG Sublimation 59 18 Promethazine Theoclate CP Direct compression 60 19 Zopiclone CCS, polyplasdone XL 10, MCC Direct compression 61 20 Levocetrizine HCl SSG, CP,CCS Direct compression 62 21 Chlorpromazine HCl SSG, CP,CCS, L-HPC, Pregelatinised Starch Direct compression 63 22 Etoricoxib CP, CCS, L-HPC, L-HPMC, SSG Direct Compression 64 23 Ibuprofen CCS, MCC, SSG Direct Compression 65 24 Metronidazole CP, Pregelatinised Starch, L-HPC Direct Compression 66 25 Nimesulide CP Direct Compression 67 26 Ketorolac Tromethamine Ac-Di-Sol, Polyplasdone XL, Explotab Direct Compression 68 27 Omeprazole & domperidone SSG, Ac-Di-Sol, Kollidon CL, Direct Compression 69 28 Tizanidine Hydrochloride CCS, SSG, CP Granules Mass Extrusion 70 29 Metronidazole SSG, Chitosan, Bamboomanna, & Direct Compression 71 Combination 30 Oxcarbazepine CP, CCS, MCC Direct Compression 72 31 granisetron hydrochloride SSG,CCS, CP Direct Compression 73 32 Aloe vera CCS, CP, SSG Dry Granulation Method 74 33 Famotidine CCS, SSG, Camphor Sublimation 75 34 Granisetron SSG, CP,CCS Wet Granulation 76 35 Aceclofenac SSG, CCS, Starch 1500 Wet Granulation method 77 36 Haloperidol CCS, SSG, CP Direct Compression Method 78 37 Furosemide CCS, Xylitol Direct Compression 79 38 Etoricoxib Menthol, CP Sublimation Technique 80 CP Crospovidone, CCS - Croscarmellose Sodium, SSG - Sodium Starch Glycolate, MCC - Microcrystalline Cellulose, L-HPC - L- Hydroxy Propyl Cellulose S.NO 1 DRUGS Granisetron Hydrochloride

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Volume 11, Issue 1, November December 2011; Article-017 Table 3: List of Currently Available Mouth Dissolving Tablets
Product Abilify Discmelt Alavert Quick Dissolving Tablets Allegra ODT Aricept ODT Benadryl Fast Melt Calpol Fast Melts Clarinex RediTabs Claritin RediTabs Clonazepam ODT FazaClo Jr. Tylenol Meltaways Klonopin Wafers Loratadine Redidose Maxalt-MLT Mirtazapine ODT Nurofen Meltlets Ondansetron ODT Orapred ODT Parcopa Prevacid SoluTab Remeron SolTab Risperdal M-Tab Unisom SleepMelts Zelapar Zofran ODT Zomig-ZMT Zyprexa Zydis Citalopram ODT Metoclopramide Zydis Reglan ODT Tramadol/Acetaminophen ODT Zolpidem ODT Manufactured by/for Otsuka America/ Bristol-Myers Squibb Wyeth Sanofi Aventis Eisai Co. Pfizer McNeil Healthcare UK Schering-Plough Schering-Plough Par Pharmaceutical AzurPharma McNeil Consumer Healthcare Roche Ranbaxy Merck & Co. Teva Pharmaceuticals Reckitt Benckiser Teva Pharmaceuticals Sciele Pharma Schwarz Pharma Takeda Pharmaceuticals Schering-Plough Janssen Chattem Valeant Pharmaceuticals Int'l GlaxoSmithKline AstraZeneca Eli Lilly and Company Biovail Salix Pharmaceuticals Schwarz Pharma Biovail Biovail Active ingredient Aripiprazole Loratadine Fexofenadine Donepezil Diphenhydramine Paracetamol Desloratadine Loratadine Clonazepam Clozapine Acetaminophen Clonazepam Loratadine Rizatriptan Mirtazapine Ibuprofen Ondansetron Prednisolone Carbidopa/levodopa Lansoprazole Mirtazapine Risperidone Diphenhydramine Selegiline Ondansetron Zolmitriptan Olanzapine Citalopram Metoclopramide Metoclopramide Tramadol/Acetaminophen Zolpidem Category Atypical antipsychotics

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Anti-histamines Anti-histamines Acetylcholinesterase inhibitors Anti-histamines Analgesics Anti-histamines Anti-histamines Benzodiazepines (Anxiety, Seizure Disorders) Antipsychotics Analgesics, Anti-pyretics Benzodiazepines Antihistamines Triptans/Serotonin agonists (acute Migraine) Antidepressants NSAIDs Antiemetics Corticosteroids Parkinson's disease Proton pump inhibitors Antidepressants Atypical antipsychotics Anticholinergic (Nighttime Sleep Aid) Parkinson's disease (MAOIs) Antiemetics Triptans/Serotonin agonists (Migraine) Atypical antipsychotics Major Depressive Disorder Antiemetics Antiemetics Opioid analgesic Hypnotics

EVALUATION OF MOUTH DISSOLVING TABLETS 2,41,42 Evaluation of MDTs is done using various tests and parameters. Following tests are performed to evaluate MDTs: 1) Weight Variation: According to I.P. procedure for uniformity of weight, twenty tablets are taken and their weight is determined individually and collectively on an electronic weighing balance. The average weight of one tablet was determined from the collective weight. The weight variation test would be a satisfactory method of determining the drug content uniformity. Average weight of Tablets (mg) percentage deviation allowed 80 mg or less More than 80 mg but less than 250 mg 250 mg or more Maximum 10 7.5 5

transformation and handling before usage depends on its hardness. Hardness in case of MDTs is kept low to allow rapid disintegration in mouth. It is done by using hardness tester like Pfizer hardness tester or Monsanto tablet hardness tester. 4) Friability: Friability is measured of mechanical strength of tablets. Roche friabilator is used to determine the friability by following procedure. A preweighed tablet is placed in the friabilator. Friabilator consist of a plasticchamber that revolves at 25 rpm, dropping the tablets at a distance of 6 inches with each revolution. The tablets are rotated in the friabilator for 4 minutes for 100 revolutions. At the end of test, tablets are reweighed; the loss in the weight of tablet is the measure of friability and is expressed in percentage as; % Friability = Loss in weight / Initial weight x 100 5) Disintegration Time: The test is carried out using the disintegration apparatus. Phosphate buffer (pH 6.8) maintained at 37C 2C is used as a disintegration media and the time taken for complete disintegration of the tablet with no palpable mass remaining in the apparatus is measured. 6) Wetting Time: A piece of tissue paper folded twice is placed in a small petridish containing 6ml. of distilled water. A tablet is carefully placed on the surface of the paper and the time required for water to reach the upper Page 91

2) Thickness: Thickness of tablets is determined using Vernier caliper. An average value is calculated by using tablets in triplicate and then the mean standard deviation values of thickness are notified. 3) Tablet Hardness: Hardness of tablet is defined as the force applied across the diameter of the tablet in the order to break the tablet. The resistance of the tablet to chipping, abrasion or breakage under condition of storage

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Volume 11, Issue 1, November December 2011; Article-017 surface of the tablet is noted as the wetting time. Less is the wetting time, indicates more porous the tablet6. 7) Water Absorption Ratio: Water absorption ratio R was determined using the equation, R=100 (Wb-Wa) / Wa Where, Wa is weight of tablet before water absorption and Wb is weight of tablet after water absorption6. 8) In vitro Drug Release Studies: The in vitro drug release is studied using USP dissolution apparatus II (paddle type) at 50 rpm in 900 ml of phosphate buffer (pH 6.8) at 370.5C. At different time intervals, 10 ml of sample is withdrawn and filtered. An equal volume of the medium is introduced into the container after each withdrawal to maintain a constant volume. The absorbance of the samples is determined by UV Spectrophotometer at given max. The mean values of drug released are plotted as cumulative % drug release vs. time. FUTURE PROSPECTIVES Future prospectives in the development of mouth dissolving tablets is bright and the various technologies used are still relatively new. Tablets prepared by these technologies have sufficient mechanical strength, quick disintegration/dissolution in the mouth without water. Various drugs which have limited bioavailability, lowmolecular weight, high permeability or which degrade rapidly in the stomach can be successfully formulated in the form of mouth dissolving tablets as these tablets are absorbed through oral cavity and thus pregastric absorption of drugs avoid hepatic metabolism, which reduces the dose and increases the bioavailability. Thus MDT may be developed for most of the drugs like anticoagulants, anti-gout agents, anti-hypertensive agents, anti-neoplastic agents & immunosuppressants, antithyroid agents, corticosteroids, lipid regulating agents, proteins, peptides and recombinant drugs, nutritional agents, neuro -muscular agents, in the near future. Now days due to advancement in technology, various manufacturing and evaluation techniques for MDTs are available and research is in process to develop other categories of drugs (which are not available in the form of MDTs) in such dosage forms. REFERENCES
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fast dissolving tablet, International Journal Of Pharma Professional's Research, 2(1), 2011, 201-205. 45. Sharma A., Jain A., Purohit A., Jatav R., Sheorey R. V., Formulation and evaluation of aceclofenac fast dissolving tablets, International Journal of Pharmacy and Life Sciences., 2(4), 2011, 681-687. 46. Rao N.G.R., Kulkarni U., Formulation and design of fast dissolving tablets of felodipine using novel co-processed superdisintegrants, International Journal of Pharma Research and Development, 2(9), 2010, 113-121. 47. Kakade S. M., Mannur V. S., Ramani K. B., Dhada A. A., Naval C. V., Bhagwat A., formulation and evaluation of mouth dissolving tablets of losartan pottasium by direct compression techniques., International Journal of Pharma Research and Development, 1(3), 2010, 290-295. 48. Rao N. G. R., Patel T., Kumar R., Development of fast dissolving carbamazepine tablets:effect of functionality of superdisintegrants, International Journal of Pharmaceutical Sciences and Nanotechnology, 3(1), 2010, 824-833. 49. Sharma S., Singh G. and Gupta G.D ., Formulation design and optimization of mouth dissolving tablets of domperidone using sublimation technique., An International Journal of Pharmaceutical Sciences, 1(1), 2010, 128-136. 50. Tiwari V., Kinikar D. J., Pillai K., Gokulan P.D., Preparation and evaluation of fast dissolving tablets of celecoxib, Journal of Current Pharmaceutical Research, 04, 2010, 411. 51. Bhardwaj V., Bansal M., Sharma P.K., formulation and evaluation of fast dissolving tablets of amlodipine besylate using defferent superdisintegrants and camphor as subliming agent, American-Eurasian Journal of Scientific Research, 5 (4), 2010, 264-269. 52. Metker V., Kumar A., Pathak N., Padhee K., Sahoo S., Formultion and evaluation of orodispersible tablets of lornoxicam, International Journal of Drug Development & Research, 3(1), 2011, 281-285. 53. Hindustan A. A., Chitta S. K., Reddy K. K., Kumar B. A., A. Chandra Sekhar., K Sushma., Sairam T., Sivaji S., A novel technique in formulation and evaluation of mouth dissolving nimesulide tablets, Journal of Advanced Pharmaceutical Research, 1(2), 2010, 101-107. 54. Gudas G. K., Manasa B., Kumaran K. S., Rajesham V.V., Kumar S. K., Kumari J. P., Reddy V. M., The effect of superdisintegrants on the dissolution of promethazine hcl fast dissolving tablets, International Journal of Pharmaceutical Sciences and Nanotechnology, 3(1), 2010, 867-871. 55. Dineshmohan S., K. Vanitha, A. Ramesh, Srikanth G., S. Akila., Formulation and evaluaton of salbutamol sulphate fast dissolving tablet, International Journal of Research in Pharmaceutical and Biomedical Sciences, 1(2), 2010, 105108. 56. Patel K. B., Shete S.N., Belgamwar V.S. , Tekade A.R.,formulation design and optimization of taste_masked mouth dissolving tablets of tramadol HCl., Asian journal of pharmaceutics, 4(3), 2010, 239-245. 57. Patel B. P., Patel J. K., Rajput G. C., Thakor R. S., Formulation and evaluation of mouth dissolving tablets of cinnarizine, Indian Journal of Pharmaceutical Sciences, 72(4), 2010, 522525.

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58. G. Arjun, Prasad M. S., Santhosha D., G. Achaiah., Formulation and evaluation of rosiglitazone mouth dissolving tablets, International Journal of Pharma and Bio Sciences, 1(1), 2010, 1-9. 59. Khemariya P., Gajbhiye K. R., Vaidya V. D., Jadon R. S., Mishra S., Shukla A., Bhargava M., Singhai S. K., Goswami S., Preparation And Evaluation Of Mouth Dissolving Tablets Of Meloxicam, International Journal Of Drug Delivery, 2(1), 2010, 76-80. 60. Sharma S., Sharma N. Gupta G. D., Formulation of FastDissolving Tablets of Promethazine Theoclate, Tropical Journal of Pharmaceutical Research October, 9 (5), 2010, 489-497. 61. Umalkar D.G., Rathinaraj B. S., Bangale G.S., Shinde G.V., Kumaraswamy D., C.H. Rajveer, K.S. Rajesh., Design And Evaluation Of Mouth Dissolving Tablet Of Zopiclone Using Different Superdisintegrants, Journal Of Pharmaceutical Sciences And Research, 2 (8), 2010, 527-533. 62. Aitha S., T. Ayyappan, S. Shanmugam, K. Sundaramoorthy, T. Vetrichelvan., Optimization, Formulation And In-Vitro Evaluation Of Mouth Dissolving Tablets Of Levocetrizine Hydrochloride For The Treatment Of Allergic Rhinitis, Journal Of Pharmaceutical Sciences And Research, 2 (9), 2010, 555-561. 63. Gudas G. K., B. Manasa, V.V. Rajesham, Kumar S. K., Kumari J. P., Formulation And Evaluation Of Fast Dissolving Tablets Of Chlorpromazine HCl, Journal Of Pharmaceutical Science And Technology, 2 (1), 2010, 99-102. 64. Chandira R. M., Venkataeswarlu B.S., Kumudhavalli M.V., Bhowmik D., Jayakar B., Formulation And Evaluation Of Mouth Dissolving Tablets Of The Etoricoxib, Pakistan Journal of Pharmaceutical Sciences, 23 (2), 2010, 178-181. 65. Jain S. K., Shukla M., Shrivastava V., Development And In Vitro Evaluation Of Ibuprofen Mouth Dissolving Tablets Using Solid Dispersion Technique, Chem. Pharm. Bull., 58(8), 2010, 1037-1042. 66. Patra S., Das P. K., Guru P. R., Development of Metronidazole Mouth Dissolving Tablets, Journal of Advanced Pharmaceutical Research, 1, 2010, 12-16. 67. Nagar M., Singhai S. K., Chopra V., Mandage K., Formulation, Evaluation and Comparision of FastDissolving Tablet of Nimesulide by Using Crospovidone as Superdisintegrant, International Journal of Pharmaceutical Sciences and Drug Research, 1(3), 2009, 172-175. 68. Patil A. B., Chakraborty S., Sarkar S., Formulation and evaluation of mouth dissolving tablet of ketorolac tromethamine for pain management by using superdisintegrants., International Journal of ChemTech Research, 1(4), 2009, 1008-1013.

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69. Singh S. K., Mishra D. N., Jassal R., Soni P., Fast Disintegrating Combination Tablets of Omeprazole and Domeperidone, Asian Journal of Pharmaceutical and Clinical Research, 2(3), 2009, 74-82. 70. Zade P. S., Formulation, Evaluation and Optimazation of fast dissolving tablets containing Tizanidine hydrochloride, International Journal of Pharm Tech Research, volume 1(1), 2009, 34-42. 71. Mohire N. C., Yadav A. V., Gaikwad V. K., Novel Approach in Development of Metronidazole Orodispersible Tablets, Research Journal of Pharmacy & Technology, 2(2), 2009, 283-286. 72. Bedi N., Kalia A., Khurana S., Formulation and evaluation of mouth dissolving tablets of Oxcarbazepine, International Journal of Pharmacy and Pharmaceutical Sciences, 1(1), 2009, 12-23. 73. Venkatalakshmi R., Sasikala C., Swathi R., Tejaswini G., Srujana.D., Kumar S., Reddy G., Kumar J. K., Formulation and evaluation of granisetron hydrochloride mouth dissolving tablet, International Journal of Pharmaceutical Sciences, 1(2), 2009, 336-341. 74. Madan J., Sharma A. K., Singh R., Fast Dissolving Tablets of aloe vera gel, Tropical Journal of Pharmaceutical research, 8(1), 2009, 63-70. 75. Furtado S., Deveswaran R., Bharath S., Basavaraj B.V., Abraham S., Madhavan V., Development and characterization of orodispersible tablets of famotidine containing a subliming agent, Tropical Journal of Pharmaceutical research, 7(4), 2008, 1185-1189. 76. Doijad. R.C., Manvi. F.V., Khalandar K.S., A comparative study on mouth dissolving tablets of Granisetron with different super disintegrants: Formulation and Evaluation, The Internet Journal of Pharmacology, 5(2), 2008, 77. Garala K.C., Ekshinge B., Jarag R.J., Shinde A.J., Fast Disintegrating Aceclofenac Tablets: Formulation Development Using Simplex Lattice Design, Thai J. Pharm. Sci., 32, 2008, 77-81. 78. Jha S.K., Vijayalakshmi P., Karki R., Goli D, Formulation and Evaluation of melt-in-mouth tablets of haloperidol, Asian Journal of Pharmaceutics, 2(4), 2008, 255-260. 79. Koseki T., Onishi H., Takahashi Y., Uchida M., Machida Y., Development of Novel Fast-Disintegrating Tablets by Direct Compression Using Sucrose Stearic Acid Ester as a Disintegration-Accelerating Agent, Chemical and Pharmaceutical Bulletin, 56(10), 2008, 1384-1388. 80. Patel D.M., Patel M.M., Optimization of Fast dissolving etoricoxib tablets prepared by sublimation technique, Indian Journal of Pharmaceutical Sciences, 70(1), 2008, 7176.

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