Hirani et al

Tropical Journal of Pharmaceutical Research, April 2009; 8 (2): 161-172 © Pharmacotherapy Group, Faculty of , University of Benin, Benin City, 300001 Nigeria. All rights reserved .

Available online at http://www.tjpr.org Review Article

Orally Disintegrating Tablets: A Review

Jaysukh J Hirani 1* , Dhaval A Rathod 1, Kantilal R Vadalia 2 1Smt. R.D.Gardi B. Pharmacy College, Rajkot-360110, 2Shri H.N.Shukla College of Pharmacy, Rajkot, Gujarat, India.


Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance. Over the past three decades, orally disintegrating tablets (ODTs) have gained considerable attention as a preferred alternative to conventional tablets and capsules due to better patient compliance. ODTs are dosage forms containing medicinal substances which disintegrate rapidly, usually in a matter of seconds, when placed on the tongue. Products of ODT technologies entered the market in the 1980s, have grown steadily in demand, and their product pipelines are rapidly expanding. New ODT technologies address many pharmaceutical and patient needs, ranging from enhanced life-cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia. This has encouraged both academia and industry to generate new orally disintegrating formulations and technological approaches in this field. The aim of this article is to review the development of ODTs, challenges in formulation, new ODT technologies and evaluation methodologies, suitability of candidates, and future prospects.

Keywords : Orally disintegrating , Improved , Texture analyser, Nanomelt TM

Received: 30 June 2008 Revised accepted: 02 November 2008

*Corresponding author: Email: [email protected]; Tel: + 91 9925062150, +91 (0)281 2488613; Fax no: +91 (0)281 2488614

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Introduction Recent market studies indicate that more than half of the patient population prefers ODTs to 10 For the past one decade, there has been an other dosage forms and most consumers enhanced demand for more patient-friendly would ask their doctors for ODTs (70%), and compliant dosage forms. As a result, the purchase ODTs (70%), or prefer ODTs to 11 demand for developing new technologies has regular tablets or (>80%) . 1 been increasing annually . Since the development cost of a new drug molecule is The US and Drug Administration Center very high, efforts are now being made by for Drug Evaluation and Research (CDER) pharmaceutical companies to focus on the defines, in the ‘Orange Book’, an ODT as “a development of new drug dosage forms for solid containing medicinal existing with improved safety and substances, which disintegrates rapidly, efficacy together with reduced dosing usually within a matter of seconds, when 12 frequency, and the production of more cost- placed upon the tongue” . The significance of effective dosage forms. these dosage forms is highlighted by the adoption of the term, “Orodispersible Tablet”, For most therapeutic agents used to produce by the European Pharmacopoeia which systemic effects, the oral route still represents describes it as a tablet that can be placed in the preferred way of administration, owing to oral cavity where it disperses rapidly before 13 its several advantages and high patient swallowing . compliance compared to many other routes 2. Tablets and hard capsules constitute a ODT products have been developed for major portion of systems that are numerous indications ranging from migraines currently available. However, many patient (for which rapid onset of action is important) to groups such as the elderly, children, and mental illness (for which patient compliance is important for treating chronic indications such patients who are mentally retarded, 14 uncooperative, nauseated, or on reduced as depression and ) . -intake/diets have difficulties swallowing these dosage forms. Those who are traveling Descriptions of Orally Disintegra- or have little access to water are similarly ting Dosage Forms 3-5 affected . ODTs are distinguished from conventional To fulfill these medical needs, pharmaceutical sublingual tablets, buccal tablets, and technologists have developed a novel oral lozenges, which require more than a minute to dosage form known as Orally Disintegrating dissolve in oral cavity. In the literature, ODTs Tablets (ODTs) which disintegrate rapidly in also are called orodisperse, mouth-dissolving, saliva, usually in a matter of seconds, without quick-dissolve, fast-melt, and freeze-dried the need to take it water. Drug dissolution and wafers. as well as onset of clinical effect and drug bioavailability may be significantly A freeze-dried wafer is a quick-dissolving, greater than those observed from thin matrix that contains a medicinal agent 6-8 conventional dosage forms . that does not need water for swallowing. This fragile dosage form requires unit- Although chewable tablets have been on the packaging to ensure physical stability. The market for some time, they are not the same wafer disintegrates instantaneously in the oral as the new ODTs. Patients for whom chewing cavity and releases drug, which dissolves or is difficult or painful can use these new tablets disperses in the saliva. The saliva is easily. ODTs can be used easily in children swallowed and the drug is absorbed across who have lost their primary teeth but do not the (GIT) 15 . 9 have full use of their permanent teeth .

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- An orally disintegrating tablet (ODT) is a • is cost-effective. solid dosage form that contains medicinal substances and disintegrates rapidly (within The Need for Development of ODTS seconds) without water when placed on the tongue. The drug is released, dissolved, or The need for non-invasive delivery systems dispersed in the saliva, and then swallowed 13 persists due to patients’ poor acceptance of, and absorbed across the GIT . and compliance with, existing delivery regimes, limited market size for drug A quick-dissolving tablet (also known as a companies and drug uses, coupled with high fast-dissolving, fast-dissolving multiparticulate, cost of disease management. rapid-dissolving, mouth-dissolving, fast- melting, or orodispersing tablets) is an oral Patient factors 17-20 tablet that does not require water for swallowing. The tablet dissolves within 60 Orally disintegrating dosage forms are seconds when placed in the mouth. The active particularly suitable for patients, who for one ingredients are absorbed through mucous reason or the other, find it inconvenient to membranes in the mouth and GIT and enter swallow traditional tablets and capsules with the blood stream. A fraction of pregastric drug an 8-oz glass of water. These include the absorption may bypass the digestive system following: and by the acids and enzymes. In general, the tablets are physically • Pediatric and geriatric patients who have robust and can be packaged in multidose 16 difficulty in swallowing or chewing solid containers . dosage forms • Patients who are unwilling to take solid Ideal properties of ODTs preparation due to fear of choking

• Very elderly patients who may not be The performance of ODTs depends on the able to swallow a daily dose of technology used during their manufacture. antidepressant. The necessary property of such tablets is the • An eight-year old with allergies who ability to disintegrate rapidly and disperse or desires a more convenient dosage form dissolve in saliva, thereby obviating the need than antihistamine for water. Various technologies have been • A middle-aged woman undergoing developed that enable ODT to perform this for breast cancer may unique function. An ideal ODT should meet be too nauseous to swallow her H - the following criteria: 2 blocker

• A schizophrenic patient in an institutional • does not require water for oral setting who may try to hide a administration yet disintegrates and conventional tablet under his or her dissolves in oral cavity within a few tongue to avoid their daily dose of an seconds atypical antipsychotic • has sufficient strength to withstand the • A patient with persistent , who rigors of the manufacturing process and may be journey, or has little or no access post-manufacturing handling to water • allow high drug loading • has a pleasant mouth feel Effectiveness factor • is insensitive to environmental conditions such as humidity and Increased bioavailability and faster onset of temperature action are a major claim of these formulations. • is adaptable and amenable to existing Dispersion in saliva in oral cavity causes pre- processing and packaging machineries gastric absorption from some formulations in

Trop J Pharm Res, April 2009; 8 (2): 163 Hirani et al those cases where drug dissolves quickly. Challenges in Formulating ODTS Buccal, pharyngeal and gastric regions are all 21 areas of absorption for many drugs . Any pre- Palatability 11,25 gastric absorption avoids first pass metabolism and can be a great advantage in As most drugs are unpalatable, orally drugs that undergo a great deal of hepatic disintegrating drug delivery systems usually metabolism. Furthermore, safety profiles may contain the medicament in a taste-masked be improved for drugs that produce significant form. Delivery systems disintegrate or amounts of toxic metabolites mediated by dissolve in patient’s oral cavity, thus releasing first-pass metabolism and gastric the active ingredients which come in contact metabolism, and for drugs that have a with the taste buds; hence, taste-masking of substantial fraction of absorption in the oral the drugs becomes critical to patient 22 cavity and pregastric segments of GIT . compliance.

Manufacturing and marketing factors Mechanical strength 19,26,27

Developing new drug delivery technologies In order to allow ODTs to disintegrate in the and utilizing them in product development is oral cavity, they are made of either very critical for pharmaceutical industries to porous and soft-molded matrices or survive, regardless of their size. As a drug compressed into tablets with very low nears the end of its patent life, it is common compression force, which makes the tablets for pharmaceutical manufacturers to develop friable and/or brittle, difficult to handle, and a given drug entity in a new and improved often requiring specialized peel-off blister dosage form. A new dosage form allows a packing that may add to the cost. Only few manufacturer to extend market exclusivity, technologies can produce tablets that are unique product differentiation, value-added sufficiently hard and durable to allow them to product line extension, and extend patent be packaged in multidose bottles, such as protection, while offering its patient population Wowtab ® by Yamanouchi-Shaklee, and a more convenient dosage form. This leads to Durasolv ® by CIMA labs. increased revenue, while also targeting underserved and under-treated patient Hygroscopicity 28 23 populations . Several orally disintegrating dosage forms are As examples, Eisai Inc. launched Aricept hygroscopic and cannot maintain physical ODT, a line extension of donepezil for integrity under normal conditions of Alzheimer’s disease, in Japan in 2004 and in temperature and humidity. Hence, they need the U.S. in 2005 in response to a generic protection from humidity which calls for challenge filed in the U.S. by Ranbaxy. specialized product packaging. Merck’s Japanese subsidiary launched Lipola M (simvastatin ODT), a line extension of its Amount of drug 11,14 ® block-buster, Zocor , a cholesterol-lowering drug, in response to seventeen generic The application of technologies used for ODTs registrations of simvastatin applied for in 24 is limited by the amount of drug that can be Japan in 2004 . incorporated into each unit dose. For lyophilized dosage forms, the drug dose must Marketers build a better brand and company be lower than 400 mg for insoluble drugs and image when they offer a unique easier-to-take less than 60 mg for soluble drugs. This form that satisfies the need of an underserved parameter is particularly challenging when patient population. formulating a fast-dissolving oral films or wafers.

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Aqueous solubility 7,29 significantly higher plasma levels have been observed, pregastric absorption leading to the Water-soluble drugs pose various formulation avoidance of first-pass metabolism may play challenges because they form eutectic an important role. This situation may have mixtures, which result in freezing-point implications for drug safety and efficacy, depression and the formation of a glassy solid which may need to be addressed and that may collapse upon drying because of loss assessed in a marketing application for an of supporting structure during the sublimation ODT 33 . For example, safety profiles may be process. Such collapse sometimes can be improved for drugs that produce a significant prevented by using various matrix-forming amount of toxic metabolites mediated by first- such as mannitol than can induce pass liver metabolism and gastric metabolism crystallinity and hence, impart rigidity to the and for drugs that have a substantial fraction amorphous composite. of absorption in the oral cavity and segments of the pregastric GIT. Size of tablet 30 Drugs having ability to diffuse and partition The degree of ease when taking a tablet into the epithelium of the upper GIT (log P > 1, depends on its size. It has been reported that or preferable > 2); and those able to permeate the easiest size of tablet to swallow is 7-8 mm oral mucosal tissue are considered ideal for while the easiest size to handle was one ODT formulations. Patients who concurrently larger than 8 mm. Therefore, the tablet size take anticholinergic may not be that is both easy to take and easy to handle is the best candidates for these drugs. Similarly, difficult to achieve. patients with Sjögren’s syndrome or dryness of the mouth due to decreased saliva Selection of ODT Drug Candidates production may not be good candidates for 20 these tablet formulations . Drugs with a short Several factors must be considered when half-life and frequent dosing, drugs which are selecting drug candidates for delivery as ODT very bitter or otherwise unacceptable taste dosage forms. In general, an ODT is because taste masking cannot be achieved or formulated as a bioequivalent line extension of those which require controlled or sustained an existing oral dosage form. Under this release are unsuitable candidates of rapidly circumstance, it is assumed that the dissolving oral dosage forms. absorption of a drug molecule from the ODT occurs in the postgastric GIT segments, Researchers have formulated ODT for various similar to the conventional oral dosage form. categories of drugs used for therapy in which But this scenario may not always be the case. rapid peak plasma concentration is required to An ODT may have varying degrees of achieve the desired pharmacological pregastric absorption and thus, the response. These include neuroleptics, pharmacokinetic profiles will vary. 29 Therefore, cardiovascular agents, analgesics, anti- the ODT will not be bioequivalent to the allergic, anti-epileptics, anxiolytics, sedatives, conventional oral dosage form. For example, hypnotics, diuretics, anti-parkinsonism agents, ODT formulations of , apomorphine, anti-bacterial agents and drugs used for 34 and buspirone have significantly different erectile dysfunction . pharmacokinetic profiles compared with the same dose administered in a conventional Approaches to ODT Development dosage form 31,32. The fast disintegrating property of the tablet is It is possible that these differences may, in attributable to a quick ingress of water into the part, be attributed to the drug molecule, tablet matrix resulting in its rapid formulation, or a combination of both. If disintegration. Hence, the basic approaches to

Trop J Pharm Res, April 2009; 8 (2): 165 Hirani et al develop rapidly dissolving oral dosage forms bioavailability requirements and the include maximizing the porous structure of the application of methods to overcome oral tablet matrix, incorporating the appropriate absorption barriers. Other areas include: the disintegrating agent and using highly water- incorporation of encapsulated APIs to achieve soluble excipients in the formulation 35 . As is modified-release profiles within the often the case, a technology that is originally convenience of an ODT; and the further developed to address a particular development of superdisintegrants for administration need can quickly become incorporation into conventional, compressed adopted as part of a pharmaceutical tablets, potentially widening the opportunity for company’s product life cycle management ODT development to non-specialist strategy, which is precisely what has companies. happened with ODT technologies. Several patented technologies with their basis of Another emerging area is the wider formulation are listed in Table 1. application of ‘oral thin-strip technologies’. The use of thin-film strips is of growing interest in The technologies that have been used by the pharmaceutical sector following the various researchers to prepare orally success of Listerine PocketPaks ® in the disintegrating dosage forms include: Freeze- United States. Thin-film strip technology uses Drying or Lyophilization, Molding, Direct a range of water-soluble and is Compression, Disintegrant addition, reported to be able to incorporate water- Sublimation, Spray Drying, Mass Extrusion, soluble, insoluble, or taste-masked Cotton-candy process, NanoCrystal TM ingredients. The film is manufactured as a Technology, Oral films/wafers. Specific continuous sheet and then cut into individual properties of the various ODT technologies doses prior to packing. The major limitations are listed in Table 2. to this technology are the relatively low doses that can be accommodated (approximately 30 Broadening the scope of ODT technologies mg) and its moisture sensitivity thus requiring specific unit-dose packaging to protect the Industry observers point to broadening uses of product and ensure shelf life. Thin-film ODT technology. These include the technology has primarily been used in over- incorporation of macromolecules using ODT the-counter (OTC) products 36 (see Table 3). into vaccines. The success for other peptide Companies with oral thin-film technologies and products will depend on

Table 1: Some ODT patents

Technology Basis Patent owner Zydis Lyophilization R.P.Scherer Inc. Quicksolv Lyophilization Janseen Pharmaceutica Lyoc Lyophilization Farmlyoc Flashtab Multiparticulate Ethypharm Compressed Tablets Orasolv, Compressed Tablets Cima Labs Inc. Durasolv RapiTab Compressed Tablets Schwarz Pharma WOWTAB Compressed Molded Yamanouchi Pharma Tablets Technologies, Inc. Fast melt Molding Élan Corp. Ziplets Molding Eurand FlashDose Cotton-candy process Fuisz Technology Ltd.

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Table 2: Advantage and disadvantages of patented technologies

Technique Novelty Advantage(s) Disadvantage(s) Zydis First to market, Freeze Quick dissolution, Expensive process, poor dried Self-preserving, stability at higher increased temperatures and bioavailability humidities Orasolv Unique taste-masking, Taste-masking is two- Low mechanical strength lightly compressed fold, quick dissolution Durasolv Compressed dosage Higher mechanical Inappropriate with larger form, Proprietary taste strength than Orasolv, doses. masking. good rigidity Flash Dose Unique spinning High surface area for High temperature required mechanism to produce a dissolution. to melt the matrix can limit floss-like crystalline he use of heat-sensitive structure, much like drugs, sensitive to moisture cotton candy. and humidity. Flashtab Compressed dosage form Only conventional containing drug as tableting technology is -- microcrystals. required. Wowtab Combination of low- Adequate dissolution No significant change in mouldability and high- rate and hardness. bioavailability. mouldabiity saccharides. SMOOTHMELT action gives superior mouth feel. Oraquick Uses patented taste- Faster and efficient masking technology. production, appropriate -- for heat-sensitive drugs Ziplet Incorporation of water- Good mechanical As soluble component insoluble inorganic strength, handling dissolves, rate of water excipients for excellent problems during diffusion in to tablet is physical performance manufacturing are decreased because of avoided, satisfactory formation of viscous properties can be concentrated . obtained at high dose (450 mg) and high weight (850 mg)

Table 3: Some oral thin-film pharmaceuticals and nutraceuticals

Manufacturer Product Drug or supplement Novartis Theraflu Thin Strips Long Acting Dextromethorphan Novartis Theraflu Thin Strips Multi-Symptom Diphenhydramine Novartis ThaminicThin Strips Long Acting Cough Dextromethorphan Novartis Triaminic Thin Strips Cough & Runny Nose Diphenhydramine Novartis Gas-X Thin Strip Anti Gas Simethicone Prestige Brands Little Colds Sore Throat Strips Pectin (from vitamin C) InnoZen Suppress Cough Strips Dextromethorphan InnoZen Suppress Herbal Cough Relief Strips Menthol Prestige Brands Chloraspetic Relief Strips Benzocaine; menthol

Trop J Pharm Res, April 2009; 8 (2): 167 Hirani et al and products include LTS Lohmann Therapy the tablets; a lower wetting time implies a Systems (West Caldwell, NI), Adhesives quicker disintegration of the tablet. For this Research (Glen Rock, PA), Applied Pharma purpose, a tablet is placed on a piece of tissue Research (Balerna, Switzerland), and Meldex paper folded twice and kept in a small Petri International (Cambridge, UK)37 . dish (ID = 6.5 cm) containing 6 ml of water, and the time for complete wetting is Elan’s proprietary NanoCrystal technology measured 39 . (Nanomelt TM )38 can enable formulation as well as improve compound activity and final Disintegration test product characteristics. Decreasing particle size increases the surface area, which leads The time for disintegration of ODTs is to an increase in dissolution rate. This can be generally less than one minute and actual accomplished predictably and efficiently using disintegration time that patient can experience NanoCrystal technology. NanoCrystal ranges from 5-30 seconds. The standard particles are small particles of drug substance, typically less than 1000 nm in diameter, which procedure of performing disintegration test for are produced by milling the drug substance these dosage forms has several limitations using a proprietary wet milling technique. This and they are not suitable for the measurement technology provides for pharmacokinetic of very short disintegration times. The method benefits of orally administered nanoparticles needs to be modified for ODTs as (less than 2 microns) in the form of a rapidly disintegration is required without water; thus disintegrating tablet matrix and wide range of the test should mimic disintegration in salivary doses (up to 200mg of API per unit). contents. A modified dissolution apparatus is

NanoCrystal colloidal dispersions of drug applied to an ODT with a disintegration time substance are combined with water-soluble that is too fast to distinguish differences GRAS (generally regarded as safe) between tablets when the compendial method ingredients, filled into blisters, and lyophilized. is used. A basket sinker containing the tablets The resultant wafers are remarkably robust, is placed just below the water surface in a yet dissolve in very small quantities of water in container with 900 mL of water at 37 0C, and a seconds. This approach is especially paddle rotating at 100 rpm is used. The attractive when working with highly potent or hazardous materials because it avoids disintegration time is determined when the manufacturing operations (granulation, tablet has completely disintegrated and 40 blending, and tableting) that generate large passed through the screen of the sinker . quantities of aerosolized and present Various scientists 41 have developed new in much higher risk of exposure. vitro methods that allow an accurate determination of disintegration test. The ODT Evaluation of Special Concern disintegration test is performed using a texture analyzer instrument. In this test, a flat-ended Crushing strength and friability can be cylindrical probe penetrates into the assessed as stated in pharmacopoeias. But disintegrating tablet immersed in water. As the some tests are of special concern and these include the following: tablet disintegrates, the instrument is set to maintain a small force for a determined period Wetting time of time. The plots of some distance traveled by the probe generated with the instrument’s Wetting time of dosage form is related to the software provide disintegration profile of the contact angle. It needs to be assessed to give tablets as a function of time. The plot an insight into the disintegration properties of

Trop J Pharm Res, April 2009; 8 (2): 168 Hirani et al facilitates calculation of the start and end-point emptying time were comparable with those of of the tablet disintegration. traditional tablets, capsules, or liquid forms. A decreased intersubject variability in transit 45,46 Dissolution test 42 time was also observed . Zydis also showed good therapeutic efficacy and patient 47,48 The development of dissolution methods for acceptability - particularly in children or ODTs is comparable to the approach taken for when easy administration and rapid onset of action were required (such as for patients conventional tablets, and is practically 49 ,50 identical. Dissolution conditions for drugs undergoing surgery) . The fast- listed in a pharmacopoeia monograph, is a disintegrating forms examined showed good place to start with scouting runs for a improved pharmacokinetic characteristics bioequivalent ODT. Other media such as 0.1 when compared with reference oral solid M HCl and buffer (pH 4.5 and 6.8) should be formulations. For example, the absorption rate evaluated for ODT much in the same way as of the acetaminophen Flashtab was higher than that of the brand leader, while having the their ordinary tablet counterparts. 51 It has been suggested that USP 2 paddle same bioavailability . Increased bioavailability apparatus is the most suitable and common and improved patient compliance were choice for orally disintegrating tablets, with a observed in Lyoc formulations for different drugs such as phloroglucinol 52, glafenine 52, paddle speed of 50 rpm commonly used. 53 54 , and propyphenazone . Moisture uptake studies 43 Using Zydis, all the drugs that can be absorbed through the buccal and esophageal Moisture uptake studies for ODT should be mucosa exhibited increased bioavailability and conducted to have an insight into the stability side-effect reduction. This is helpful particularly in actives with marked first-pass of the formulation, as several excipients used 44 are hygroscopic. Ten tablets from each hepatic metabolism . Finally, the suitability of formulation are kept in a desiccator over ODTs for long-term therapy was also calcium chloride at 37 0C for 24 h. The tablets assessed. Lyoc formulations containing aluminum were positively tested in patients are then weighed and exposed to 75% RH at 55 room temperature for two weeks. The required with gastrointestinal symptoms . humidity (75% RH) is achieved by keeping 20 saturated sodium chloride solution at the Counseling points for ODTs bottom of the desiccator for three days. One tablet as control (without superdisintegrant) is Pharmacists are in the ideal position to kept to assess the moisture uptake due to become familiar with the various technologies, other excipients. Tablets are weighed and the and educate their patients on what to expect percentage increase in weight is recorded. upon taking their first dose. The majority of patients receiving ODT formulations have little Clinical studies understanding of this new dosage form. Patients may be surprised when tablets begin In vivo studies have been performed on oral to dissolve in the oral cavity. They might fast-disintegrating dosage forms to investigate expect a faster onset of therapeutic action. their behavior in the oral–esophageal tract, Clarification from the pharmacist can avoid their pharmacokinetic and therapeutic any confusion or misunderstanding. Although efficacy, and acceptability. Zydis’s residence no water is needed to allow the drug to time in the mouth and stomach, and its transit disperse quickly and efficiently, most through the esophageal tract, was technologies utilize the body’s own salivation. investigated using gamma-scintigraphy. Its Decreased volume of saliva may slow the rate dissolution and buccal clearance was rapid 44; of disintegration/dissolution and decrease the the esophageal transit time and stomach bioavailability of the product.

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Although chewable tablets have been in the stability of the product and also develop market for some time, they are not the same a cost-effective product as the new ODTs. Patients for whom chewing • To arrive at various taste-masking is difficult or painful can use these new tablets agents and prepare palatable dosage easily. ODTs can be used easily in children forms thereby increasing patient who have lost their primary teeth, but do not compliance have full use of their permanent teeth. • To develop disintegrants from different Patients may mistake ODTs for effervescent polymers which are used as coating tablets. Pharmacists may wish to stress the materials by certain modifications and difference between the use of ODTs and use them for formulating ODTs effervescent tablets. Future Prospects ODT formulations are more susceptible to degradation via temperature and humidity. These dosage forms may be suitable for the Some of the newest ODT formulations are oral delivery of drugs such as protein and dispensed in a conventional stock bottle. peptide-based therapeutics that have limited Pharmacists are advised to take care when bioavailability when administered by dispensing such formulations to ensure they conventional tablets. These products usually are not exposed to high levels of moisture or degrade rapidly in the stomach. Should next humidity. As with most drugs, patients should generation drugs be predominantly protein or be advised to avoid storing ODTs in the peptide based, tablets may no longer be the medicine cabinet in the bathroom. dominant format for dosing such moieties. Injections generally are not favored for use by Pharmacists have been alerted to exercise patients unless facilitated by sophisticated additional care when dispensing new auto-injectors. is one good prescriptions for ODT formulations. Most such alternative system to deliver these drugs, but products are available in the same strengths the increased research into biopharma- as traditional dosage forms. Prescribing ceuticals so far has generated predominantly physicians must make an additional notation chemical entities with low molecular weights. for the dispensing of an ODT. A physician The developments of enhanced oral protein may also mistakenly believe the drug brand delivery technology by ODTs which may name is Zydis, for example, without identifying release these drugs in the oral cavity are very a specific drug. Verification with the promising for the delivery of high molecular prescribing practitioner may be necessary in weight protein and peptide. some cases and can clear up any confusion. Conclusion Industrial Applications Orally disintegrating tablets have better Industrial applications include the following: patient acceptance and compliance and may offer improved biopharmaceutical properties, • To develop an orally disintegrating improved efficacy, and better safety compared dosage forms and to work with existing with conventional oral dosage forms. disintegrants Prescription ODT products initially were • To further improvise upon the existing developed to overcome the difficulty in technology of ODTs swallowing conventional tablets among • To optimize the blend of disintegrants or pediatric, geriatric, and psychiatric patients excipients to achieve ODTs with dysphagia. Today, ODTs are more widely • To select and develop proper packaging available as OTC products for the treatment of material and system for enhanced allergies, cold, and flu symptoms. The target population has expanded to those who want

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