Oral Disintegrating Tablets: An Overview

Transcription

1 International Journal of Chemical and Pharmaceutical Sciences 2010, Dec., Vol.1 (2) ISSN: ABSTRACT Oral Disintegrating Tablets: An Overview *Velmurugan S and Sundar Vinushitha KLR Pharmacy College, Palvoncha, Khammam, Andhra Pradesh, India. *corresponding author: - [email protected] Oral drug delivery remains the most preferred route for administration of various therapeutic agents. Recent advances in technology prompted researchers and scientists to develop oral disintegrating tablets (ODTs) with improved patient convenience and compliance. ODTs are solid unit dosage form which dissolve or disintegrate rapidly in the mouth without water or chewing. Novel ODT technologies address many patient and pharmaceutical needs such as enhanced life cycle management to convenient dosing particularly for pediatric, geriatric and psychiatric patients who have difficulty in swallowing (Dysphagia) conventional tablet and capsules. Technologies used for manufacturing of ODTs are either conventional technologies or patented technologies. This review depicts the various aspects of ODT formulation, superdisintegrants and technologies developed for ODT, along with various drugs explored, evaluation tests and marketed formulations in this field. Keywords: Disintegration, Oral disintegrating tablets, Superdisintegrant. 1. Introduction The oral route of administration is considered as the most widely accepted route because of its convenience of self administration, compactness and easy manufacturing. [1-2] But the most evident drawback of the commonly used oral dosage forms like tablets and capsules is difficulty in swallowing, leading to patients incompliance particularly in case of pediatric and geriatric patients [1], but it also applies to people who are ill in bed and to those active working patients who are busy or traveling, especially those who have no access to water. [2] Over a decade, the demand for development of orally disintegrating tablets (ODTs) has enormously increased as it has significant impact on the patient compliance. Orally disintegrating tablets are appreciated by a significant segment of populations particularly who have difficulty in swallowing. It has been reported that Dysphagia [3] (difficulty in swallowing) is common among all age groups and more specific with pediatric, geriatric population along with institutionalized patients,psychiatric patients and patients with nausea, vomiting, and motion sickness complications. [1] ODTs with good taste and flavor increase the acceptability of bitter drugs by various groups of population. This dosage form combines the advantages of dry and liquid formulation. Some novel ODT technology allow high drug loading, have an acceptable taste, offer a pleasant mouth felling, leaving minimal residue in the mouth after oral administration.odt have been investigated for their potential in improving bioavaibility of poorly soluble drug through enhancing the dissolution profile of the drug and hepatic metabolism drugs. Orally disintegrating tablets are also called as orodispersible tablets, quick 1

2 disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, fast dissolving tablets, rapid dissolving tablets, porous tablets, and rapimelts. However, of all the above terms, United States pharmacopoeia (USP) approved these dosage forms as ODTs. Recently, European Pharmacopoeia has used the term orodispersible tablet for tablets that disperses readily and within 3 min in mouth before swallowing. [4] Some of super disintegrants employed in ODTs are discussed in Table 1. United States Food and Drug Administration (FDA) defined ODT 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 ODTs generally ranges from several seconds to about a minute. [5] 2. Drug selection criteria The ideal characteristics of a drug for oral dispersible tablet include [6] Ability to permeate the oral mucosa. At least partially non-ionized at the oral cavity ph. Have the ability to diffuse and partition into the epithelium of the upper GIT. Small to moderate molecular weight. Low dose drugs preferably less than 50 mg. Short half life and frequent dosing drugs are unsuitable for ODT. Drug should have good stability in saliva and water. Very bitter or unacceptable taste and odor drugs are unsuitable for ODT. 3. Advantages [7,8] Easy to administer to the patient who cannot swallow such as pediatric, geriatric, bedridden, stroke victim and institutionalized patient ( specially for mentally retarded and psychiatric patients) Pregastric absorption leading to increased bioavaibility/ rapid absorption of drugs from mouth, pharynx and oesophagus as saliva passes down to stomach, also avoids hepatic metabolism. Convenient for administration to traveling patients and busy people who do not have accesses to water. Excellent mouths feel property produced by use of flavours and sweetners help to change the perception of medication as bitter pill especially in pediatric population. Fast disintegration of tablets leads to quick dissolution and rapid absorption which may produce rapid onset of action. ODTs offer all the advantages of solid dosage forms and liquid dosage forms. Convenience of administration and accurate dosing compared to liquids. 4. Desired criteria for ODTs [8-10] ODT should leave minimal or no residue in mouth after oral administration, compatible with pleasing mouth feel. Effective taste masking technologies should be adopted for bitter taste drugs. Exhibit low sensitivity to environment condition such as humidity and temperature. ODTs should dissolve / disintegrate in the mouth in matter of seconds without water. Have sufficient mechanical strength and good package design. The drug and excipients property should not affect the orally disintegrating tablets. Be portable and without fragility concern. 5. Technologies used for manufacturing of orally disintegrating tablets 2

3 Various processes employed in formulating ODTs including conventional technologies and patented technologies. Table 4 enlisted the various drugs explored for developing ODTs 5.1. Conventional Technologies Freeze drying or lyoplilization A process, in which water is sublimated from the product after freezing, is called freeze drying. Freeze- dried forms offer more rapid dissolution than other available solid products. The lyophilization processes imparts glossy amorphous structure to the bulking agent and some times to the drug, Table 1: Superdisintegrants employed in ODT Super disintegrants Crosscarmellose Crosspovidone Aliginic acid NF Soy polysaccharides Calcium silicate Sodium starch glycolate Ion resin L-HPC exchange Acrylic acid derivatives Nature Modified cellulose or Cross linked cellulose Cross linked PVP Cross linked Aliginic acid Natural disintegrant Modified starch Resins Low hydroxyl propyl cellulose Poly (Acrylic acid) Superporous Mechanism of Action Wicking due to fibrous structure swelling with minimal gelling Water wicking, swelling and possibly some deformation recovery Wicking action Wicking action Rapid and extensive swelling with minimal gelling Both swelling and wicking Wicking action Brand Names Ac-Di-Sol Nymce 25 X Nymcel Kollidon Polyplasdone Satialgine EMCOSOY Explotab Primogel Amberlite (IPR 88) Sodium Alginate Effervescent mixture hydrogel Sodium salt of Alginic acid Citric acid, tartaric acid and sodium bicarbonate Swelling Effervescence thereby enhancing the dissolution characteristic of the formulation. The entire freeze drying process is done at nonelevated temperature to eliminate adverse thermal effects that may affect drug stability. The major disadvantages of lyophilization technique are that it is expensive and time consuming; fragility makes conventional packaging unsuitable for these products and poor stability under stressed conditions and their limited ability to accommodate adequate concentration of drugs.[11-15] Direct compression Easiest way to manufacture tablets is direct compression. Low manufacturing cost, conventional equipments and limited number of processing steps led this technique to be a preferable one. However disintegration and dissolution of directly compressed tablets depend on single or combined effect of disintegrant, water soluble excipients and effervescing agents. It is essential to choose a suitable and an optimum concentration of disintegrant to ensure quick disintegration and dissolution. Superdisintegrants are newer substances which are more effective at lower concentrations with greater disintegrating efficiency and mechanical strength. On contact with water the superdisintegrants swell, hydrate, change volume or form and produce a disruptive change in the tablet. Effective superdisintegrants provide improved compressibility, compatibility and have no negative impact on the mechanical strength of formulations containing high dose drugs. The type of disintegrants and its proportion are of prime importance. Also factors to be considered 3

4 are particle size distribution, contact angle, pore size distribution and water absorption capacity. Studies revealed that the water insoluble superdisintegrants like sodium starch glycolate and Croscarmellose sodium show better disintegration property than the slightly water soluble agents like Crospovidone, since they do not have a tendency to swell. Superdisintegrants that tend to swell show slight retardation of the disintegration property due to formation of viscous barrier. There is no particular upper limit regarding the amount of superdisintegrant as long as the mechanical properties of the tablet are compatible with its intended use. The superdisintegrant may be used alone or in combination with other superdisintegrants. [7,16] Molding Molded tablets, usually prepared from soluble ingredients, by compressing a powder mixture which is moistened with a solvent, into mould plates to form a wetted mass. Recently, molded forms have been prepared directly from a molten matrix, in which the drug is dissolved or dispersed or by evaporating the solvent from a drug solution or suspension at a standard pressure. Usually molded tablets are compressed at a lower pressure than are conventional are conventional tablets, and posses a porous structure that hastens dissolution. To improve the dissolution rate, the powder blend usually has to be passed through a very fine screen. Tablet produced by molding are solid dispersion. Molded tablets disintegrate more rapidly and offer improved taste because the dispersion matrix is in general made from water soluble sugars. The active ingredients in most cases are absorbed through the mucosal lining of the mouth. Unfortunately, moulded tablets typically do not possess great mechanical strength. Erosion and breakage of the moulded tablets often occurs during tablet handling and when blister pockets are opened. Hardness agents can be added to the formulation, but then the rate of tablet solubility usually decreases. [16,17] Mass extrusion 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 shaped extrude which are finally cut into even segments using heated blade to form tablets. This process can also be used to coat granules of bitter drugs to mask their taste. Mass extrusion was the technique used for preparing taste masked granules. The tablet was prepared with different super disintegrate e.g. sodium starch glycolate, croscarmellose sodium and crosspovidone etc. [18,19] Melt granulation Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a melt able binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. For accomplishing this process, high shear mixers are utilized, where the product temperature is raised above the melting point of binder by a heating jacket or by the heat of friction generated by impeller blades. This approach to prepare FDT with sufficient mechanical integrity, involves the use of a hydrophilic waxy binder (Superpolystate, PEG-6-stearate). Superpolystate is a waxy material with a melting point of C and a HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues. [20] Phase transistion process Kuno et al proposed a novel method to prepare ODTs with sufficient hardness by involving the phase transition of sugar alcohol. In this technique,odt were produced by compressing powder containing erythritol 4

5 (melting point: 122 C) and xylitol (melting point: C), and then heating at about 93 C for 15 min. After heating, the median pore size of the tablets was increased and tablet hardness was also increased. Heating process enhances the bonding among particles leading to sufficient hardness of tablets which was otherwise lacking owing to low/little compactibility. [21] Sublimation The slow dissolution of the compressed tablet containing even highly water soluble ingredients is due to the fact that the low porosity of the tablets reduces water penetration into the matrix. When inert volatile solid ingredie nts like ammonium bicarbonate, ammonium carbonate, benzoic acid, camphor, hexameth ylene tetramine, naphthalene, phthalic anhydride, urea and urethane were added to along with other tablet excipients and the blend was compressed in to a table, which are finally subjected to a process of sublimation resulting in highly porous structures. Sublimation has been used to produce MDTs with high porosity. These compressed tablets exhibit good mechanical strength and have high porosity (approximately 30%) rapidly dissolved within 15 seconds in saliva. [22] 5.2. PATENTED TECHNOLOGIES Zydis technology Zydis was the first marketed technology developed by R.P.Scherer,Inc. for formation of new generation tablets.zydis, the best known of the fast dissolving/disintegrating tablet preparations was the first marketed new technology tablet. The tablet dissolves in the mouth within seconds after placement on the tongue.zydis formulation is a unique freeze dried tablet in which drug is physically entrapped or dissolve in a matrix composed of two components, a saccharide e.g. mannitol and a polymer. When Zydis units are kept in the mouth the freeze dried structure disintegrates instantaneously and does not require water for swallowing. Polymers such as gelatin, dextran or are incorporated to impart strength during handling. Mannitol or sorbitols are incorporated, to obtain crystallanity, elegance and hardness. Flocculating agents (e.g, xanthan gum and acacia) to provide uniform dispersion of drug particles; preservatives(e.g., parabens) to prevent microbial growth; permeation enhancers(e.g., sodium lauryl sulphate) to improve transmucosal permeability; ph adjusters(e.g, citric acid) to optimize chemical stability; flavours and sweetners to improve patient compliance Water is used in the manufacturing process to ensure production of porous units to achieve rapid disintegration. Gums prevent the sedimentation of dispersed particles in manufacturing process. Collapse protectants like gelatin prevents the shrinkage of Zydis units during freeze-drying process or on long term storage. The product is very light weight and fragile, and must be dispensed in a special blister pack. [13,23] Orasolv technology OraSolv was Cima's first fastdissolving/disintegrating dosage form. In this system active medicament is taste masked, contains disintegrating agent. The disintegration of ODT in the mouth is cause by the action of an effervescent agent, activated by saliva. The amount of effervescent agent is in general about 20-25% of the total weight of the tablet. The widely used effervescent disintegration pair usually include an acid source (citric, tartaric, malic, fumeric, adipic and succinics ) and a carbonate source (sodium bicarbonate, sodium carbonate, potassium bicarbonate and potassium carbonate, magnesium carbonate).the microspheres are loosely compressed to maintain the integrity of the coating.the major disadvantage of the OraSolv formulations is its mechanical strength. For that reason, Cima developed a special handling and packaging system for OraSolv. Manufacturing requires a controlled environment at low relative humidity 5

6 and protection of the final tablets with moisture impermeable blisters. [13,24] Durasolv technology Durasolv is CIMA s second generation fast dissolving or disintegrating tablet formulation to produce stronger tablets for packing in conventional blisters or bottles. Durasolv has much higher mechanical strength due to use of the higher compaction pressure during tabletting. One disadvantage of Durasolv is that the technology is not compatible with larger doses of active ingredients, because the formulation is subjected to high pressure during compaction. The drug powder coating in Durasolv may become fractured during compaction, exposing the bitter tasting drugs to the patient taste buds.so This technology is good for tablets having low amount of active ingredients. [19] Wow tab technology The WOW in the WOWTAB signifies the tablet is to be given without water. This technology utilizes sugar and sugar-like excipients. The two different types of saccharides are combined to obtain a tablet formulation with adequate hardness and fast dissolution rate. The two different saccharides are those with high moldability like maltose, mannitol, sorbitol, and oligosaccharides.(good binding property) and low moldability like lactose, glucose, mannitol, xylitol (rapid dissolution). Tablets produced from this technology will have 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. Due to the significant hardness the WOWTAB formulation is more stable to the environment than the Zydis and Orasolv. Erythritol was found to be the best sugar for this type of formulation, showing rapid disintegration which is unaffected by tablet hardness. [13,25] Cotton candy technology This process is so named as it utilizes an inimitable spinning mechanism to produce floss like crystalline structure, which mimics cotton candy. The cotton candy process also known as the candy floss process. A mouth dissolving tablet is formed using candy floss or shear form matrix.it involves the formation of matrix of polysaccharides or saccharides by simultaneous action of flash melting and spinning. The matrix formed is partially recrystallised to have improved flow properties and compressability. This candy floss matrix is then milled and blended with active ingredients, excipients and subsequently compressed to ODT. This process can accommodate larger drug doses and offer improved mechanical strength. However, high process temperature limits the use of this process. [24,25] Oraquick technology The Oraquick fast dissolving/ disintegrating tablets formulation utilizes a patented taste masking technology. This taste masking process does not utilize solvents of any kind, so leads to faster and more efficient production. During processing low-heat is produced so this technique is suitable for heat sensitive drugs. KV pharmaceuticals also claims that the matrix that surrounds and protects the drug powder in microencapsulated particle is more pliable.this technique gives tablets with good taste masking and quick dissolution in matter of seconds. [26] Nanocrystal technology NanoCrystal Fast dissolving technology provides for: Pharmacokinetic benefits of orally administered nanoparticles (<2 microns) in the form of a rapidly disintegrating tablet matrix.nano Crystal colloidal dispersions of drug substance are combined with water-soluble GRAS (Generally Regarded As Safe) ingredients, filled into blisters, and lyophilized. This method avoids manufacturing process such as granulation, blending and tabletting which is more 6

7 advantages for highly potent and hazardous drugs.for fast dissolving tablets, Elans proprietary Nanocrystal technology can enable formulation and improve compound activity and final product characteristics. Decreasing particle size increases the surface area,which leads to an increase dissolution rate. [27] Shearform technology In this technology, a shearform matrix, Floss is prepared. Feedstock prepared with a sugar carrier is subjected to flash heat processing. In this process, sugar is simultaneously subjected to centrifugal force and to a temperature gradient, which causes the temperature of the mass to rise and hence an internal flow condition is created, permitting part of it to move with respect of the mass. This is followed by its exit through the spinning head that flings the floss under centrifugal force and draws into long and thin floss fibres, which are usually amorphous in nature.the floss so produced is further chopped and recrystallised to provide a uniform flow, thus facilitate blending. Then the recrystallised matrix, active drug and other excipients are blended together and finally compressed into tablets. Active drug and other excipients may be blended with the floss before recrystallising it. The tablets manufactured by this process are highly porous in nature and offer very pleasant mouth feel due to rapid solubilisation of sugars in presence of saliva.[27] Pharmaburst technology Pharmaburst technology is patented by SPI pharma. Pharmaburst technology uses off the shelf coprocessed excipients to create an ODT that, depending on the type of active ingredients and loading, dissolves within seconds. The quantity of pharmaburst required in a formulation depends on the active ingredients in the tablet. The process involves a dry blend of a drug, flavor and lubricant that are compressed into a tablet on a standard tablet press with stock tooling. The manufacture process can be carried out under normal temperature and humidity conditions. The tablets can be packaged in blister packs or bottle. [28] Frosta technology Akina patents this technology. The core concept of Frosta technology is compressing highly plastic granules at low pressure to produce strong tablets with high porosity. The highly plastic granules comprise three classes of components: a porous and plastic material, a water penetration enhancer, and a binder. The process involves mixing the porous plastic material with water penetration enhancer followed by granulating with binder. The technology can be used for almost any drugs including aspirin, loratidine, caffeine, and folic acid, vitamins and dietary supplements. The highly plastic granule approach produces fast melting pharmaceutical tablets with excellent hardness and fast disintegration time ranging from several seconds to 30 seconds, depending on the size of the tablets. [28] 6. EVALUATION OF ODTs Evaluation parameters of tablets mentioned in the Pharmacopoeias need to be assessed, along with some special tests are discussed here Hardness A significant strength of ODT is difficult to achieve due to the specialized processes and ingredients used in the manufacturing. The limit of hardness for the ODT is usually kept in a lower range to facilitate early disintegration in the mouth. The hardness of the tablet may be measured using conventional hardness test Friability To achieve % friability within limits for an ODT is a challenge for a formulator since all methods of manufacturing of ODT are responsible for increasing the % friability values. Thus, it is necessary that this parameter should 7

8 be evaluated and the results are within bound limits ( %). Table.2 ODT products available in international market Nimpain MD Nimesulide Prompt cure pharma Imodium lingual Imodium R.P. Scherer Corp., U.S.A Pepcidin Rapitab Pepcid Merck & Co., U.S.A Calritin Reditabs Calritin Schering Plough, U.S.A Nurofen Flashtab Ibuprofen Boot healthcare Hyoscyamine sulfate ODT Hyoscyamine sulfate Ethex Corporation Cibalginadue Fast Ibuprofen Novartis Consumer Health Zyprexa Olanzepine Eli Lilly Zofran ODT Ondansetron Glaxo Smithkline Risperdal M Tab Risperidone Janssen Imocdium Instant Melts Propulsid Quick Sol Zomig-ZMT and Rapimelt Lopermide HCl Cisapride monohydrate Zolmitriptan Janssen Janssen Astra Zeneca Alavert Loratadine Wyeth Consumer Healthcare NuLev Hyoscyamine Sulfate Schwarz Pharma Kemstro Baclofen Schwarz Pharma Benadryl Melt Fast Diphenhydramine Citrate Pfizer Nasea OD Ramosetoron HCl Yamanouchi Gaster D Famotidine Yamanouchi Excedrin Tabs Quick Acetaminophen Bristol-Myers Squibb Zolpidem ODT Zolpidem tartrate Biovail Fluoxetine ODT Fluoxetine Biovail 6.3. Wetting time and water absorption ratio Wetting time of dosage form is related to with the contact angle. Wetting time of the ODT is another important parameter, which needs to be assessed to give an insight into the disintegration properties of the tablet. Lower wetting time implies a quicker disintegration of the tablet. The wetting time of the tablets can be measured by using the simple procedure. [29] Five circular tissue papers of 10cm diameter are placed in a petridish. Ten milliliters of water soluble dye solution is added to petridish. A tablet is carefully placed on the surface of the tissue paper. The time required for water to reach upper surface of the tablet is noted as the wetting time. For measuring water absorption ratio the weight of the tablet before keeping in the petridish is noted (Wb). The wetted tablet from the petridish is taken and reweighed (Wa). The water absorption ratio, R can be the determined according to the following equation. R = 100 (Wa-Wb) / Wb 6.4. Moisture uptake studies Moisture uptake studies for ODT should be conducted to assess the stability of the formulation. Ten tablets from each formulation were kept in a dessicator over calcium chloride at 37 0 C for 24h. The tablets were then weighed and exposed to 75% relative humidity, at room temperature for 2 weeks. Required humidity was achieved by keeping saturated sodium chloride solution at the bottom of the dessicator for 3 days. One tablet as control (without super disintegrants) was kept to assess the moisture uptake due to other excipients. Tablets were weighed and the percentage increase in weight was recorded Disintegration test The time for disintegration of ODTs is generally <1min and actual the disintegration time that patients can experience ranges from 5 to 30s. The standard procedure of performing disintegration test for these dosage forms has several limitations and they do not suffice the measurement of very short disintegration times. The disintegration test for ODT should mimic disintegration in mouth with in salivary contents. 8

9 6.6. Dissolution test The development of dissolution methods for ODT is comparable to approach taken for conventional tablets and is practically identical when ODT does not utilize taste masking. Commonly the drugs may have dissolution conditions as in USP monograph. Other media such as 0.1 N HCl, ph 4.5 and ph 6.8 buffers should be used for evaluation of ODT in the same way as their ordinary tablet counterparts. Experience has indicated that USP 2 paddle apparatus is most suitable and common choice for dissolution test of ODT tablets, where a paddle speed of 50 rpm is commonly used. Typically the dissolution of ODTs is very fast when using USP monograph conditions. Hence slower paddle speeds may be utilized to obtain a comparative profile. Large tablets approaching or exceeding one gram and containing relatively dense particles may produce a mound in the dissolution vessel, which can be prevented by using higher paddle speeds. These two situations expand the suitable range of stirring to rpm. The USP 1 (basket) apparatus may have certain applications for ODT but is used less frequently due to specific physical properties of tablets. Table 3: ODT products in Indian market: Brand Name Active Ingredients Company Nimulid-MD Nimesulide Panacea Biotech Zyrof meltab Rofecoxib Zydus Cadila MOSID-MD Mosapride Citrate Torrent Pharmaceuticals Feledine Melt Piroxicam Pfizer Maxalt ODT Famotidine Merck Remeron Sol Tab Mirtazapine Organon Romilast Montelukast Ranbaxy Manza BDT Olanzepine Orchid Olanexinstab Olanzepine Ranbaxy Valus Valdecoxib Glenmark Rofaday MT Rofecoxib Lupin Torrox MT Rofecoxib Torrent Dolib MD Rofecoxib Panacea Zilflam Rofecoxib Kapron Orthoret MD Rofecoxib Biochem Nexus MD Nimesulide Lexus Nimex MD Nimesulide Mexon healthcare Nisure MD Nimesulide Suzen Pharma Olnium MD Nimesulide Olcare Lab Sulbid Nimesulide Alpic Remedies Specifically tablet fragments or disintegration tablet masses may become trapped on the inside top of the basket at the spindle where little or no effective stirring occurs, yielding irreproducible results in dissolution profile. [29,30] Table.4: Drugs explored for orally disintegrating tablet [31] Category Drugs Category Drugs Analgesics and Antiinflammat ory Agents Antibacterial Agents Arrhythm ic Agents Aloxiprin, Auranofin, Azapropazon e, Benorylate, Diflunisal, Etodolac, Fenbufen, Nabumetone, Naproxen, Oxaprozin, Oxyphenbuta zone, Phenylbutazo ne, Piroxicam, Sulindac Albendazole, Bephenium Hydroxynaph thoate,, Pyrantel Embonate, Thiabendazol e. Amiodarone, Disopyramide, Flecainide Acetate, Quinidine Epileptics Hypertensi ve Agents: Neoplastic Agents And Immunosu ppressants : Beclamide, Carbamazepine, Clonazepam, Ethotoin, Methoin, Methsuximide, Phensuximide, Primidone, Sulthiame, Valproic Acid. Amlodipine, Carvedilol, Benidipine, Darodipine,, Prazosin, Reserpine, Terazosin Aminoglutethimide, Amsacrine, Azathiopnne, Busulphan, Mitozantrone, Procarbazine, Tamoxifen Citrate, Testolactone. 9

10 Antibacterial Agents Fungal Agents: Anxiolytic, Sedatives, Hypnotics And Neurolepti Thyroid Agents Lipid Regulatin g Agents: Nitrates And Other Anginal Agents: Opioid analgesics Gastro- Intestinal Benethamine Penicillin, Demeclocycli ne, Doxycycline, Erythromycin, Ethionamide, Imipenem,, Nitrofurantoi n, Rifampicin, Spiramycin, Sulphametho xazole, Tetracycline, Amphotericin, Butoconazole Nitrate, Clotrimazole, Econazole Alprazolam, Amyiobarbito ne, Barbitone, Bentazeparn, Bromazepam, Bromperidol, Brotizoiam. Carbimazole, Propylthioura cil Bezafibrate, Clofibrate,Fe nofibrate, Gemfibrozil, Probucol Amyl Nitrate, Glyceryl Trinitrate, Isosorbide Dinitrate, Isosorbide Mononitrate, Pentaerythrito l Tetranitrate. Codeine, Dextropropyo xyphene, Diamorphine, Dihydrocodei ne, Meptazinol, Methadone, Morphine, Nalbuphine, Pentazocine. Bisacodyi, Cimetidine, Cardiac Inotropic Agents: Diuretics: Parkinsoni an Agents: Gout Agents: Histamine H,- Receptor Antagonist s: Migraine Agents: Corticoster oids: Muscarinic Amrinone, Digitoxin, Digoxin, Enoximone, Lanatoside C, Medigoxin. Acetazolarnide, Amiloride, Triamterene Bromocriptine Mesylate, Lysuride Maleate. Allopurinol, Probenecid, Sulphinpyrazone Acrivastine, Astemizole, Cinnarizine, Cyclizine, Cyproheptadine, Dimenhydrinate, Flunarizine, Loratadine, Meclozine, Oxatomide, Dihydroergotamine Mesyiate, Ergotamine Tartrate, Methysergide Maleate, Pizotifen Maleate, Sumatriptan Succinate. Prednisone, Triamcinolone, Beclomethasone, Betamethasone, Budesonide, Cortisone Desoxymethasone, Dexamethasone, Atropine, Benzhexol, Agents: Cisapride,, Sulphasaiazin e Tj- Blockers : Malarials: Acebutolol, Alprenolol, Atenolol, Labetalol, Metoptolol, Nadolol, Oxprenolol, Pindolol, Propranolol. Amodiaquine, Chloroquine, Chlorproguan il, Agents: Anti Protozoal Agents Anticoagulants : Biperiden, Benznidazole, Clioquinol, Decoquinate, Diiodohydroxyquino line,. Dicoumarol, Dipyridamole, coumalone, 7. Patient counseling points for ODT As pharmacist are ideal person to become familiar with recent technology advancement in novel dosage form, thus have opportunity to counsel the patient for effective treatment. Educating the patients about ODT can avoid any confusion and misunderstanding of this dosage form. Counseling points to the patients include: Patients may mistake ODT for effervescent tablets, pharmacist need to be clearly told about the different between them. The cima technologies orosolv and durasolv use slight effervescence, patients may experience a pleasant tingling effect on the tongue. ODT need to be handled carefully because some of ODT developed may not have sufficient mechanical strength. Patients with dryness of mouth or with siogrens syndrome or who taking anticholengic drugs may not be suitable population for administering ODT.Although no water is needed to allow the drug to dispense quickly and efficiently but most technologies of ODT utilizes the body own salivation but decreased volume of saliva may slow down dissolution/ disintegration/ bioavailability of the product. 10

11 Although chewable tablets have been in the market for long time, patients need to be counseled properly the difference between chewable and ODT tablets.odt can be used easily in children who have lost their primary teeth but do not have full use of their permanent teeth and also for geriatric patients who have lost their teeth permanently. With the pharmacist counseling, intervention and assistance all of these patients who taking ODT could be more properly treated with greater convenience. 8. CONCLUSION Orally disintegrating tablets have potential advantages over conventional dosage forms, with improved patient compliance, convenience, bioavailability and rapid onset of action. They are a very good alternative for drug delivery to geriatric and pediatric patients. They have significant advantages of both solid and liquid dosage forms, as they remain solid during storage, which aid in stability of dosage forms and transform into liquid form within few seconds after its administration. As a result of the variety of technologies for its formulation, several commercial products are available in the market. Thus ODT has tremendous scope for being the delivery system for most of the drugs in near future. 9. REFERENCES 1. Sastry SV, Nyshdham JR, Fix JA. Recent technological advances in oral drug delivery: A review. Pharmaceutical Science and Technology Today. 2000; 3: Seager H. Drug-delivery products and the Zydis fast-dissolving dosage form. Journal of Pharmacy and Pharmacology. 1998; 50(4): Lindgren S, Janzon L. Dysphagia; Prevalence of swallowing complaints and clinical findings. Medical clinics of North America., 1993; 77: Fu Y, Yang S, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets: Developments, technologies, taste-masking and clinical studies. Critical Review in Therapeutic Drug Carrier System. 2004; 21: Brown D. Orally Disintegrating Tablets- Taste over Speed. Drug Delivery Technology. 2003; 3: Kumaresan C, Orally Disintegrating Tablet - Rapid Disintegration, Sweet Taste, And Target Release Profile, pharmainfo.net sep Makino T, Yamada M. and Kikuta, J. Fast dissolving tablet and its production, 1993, European Patent A2. 8. Reddy L. H, Ghosh B, and Rajneesh. Fast dissolving drug delivery systems: a review of the literature. Indian Journal of Pharmaceutical Science. 2002; 64(4): Seager H. Drug-deliver products and the zydis fast-dissolving dosage form. Journal of Pharmacy and Pharmacology. 1998; 50: Modi A and Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS Pharm. Sci. Tech., 2006; 7(3): Reig AR, Plazas F, Galvan CJ, Heras NJ, Artes FM and Gabarron HE. Acceptance survey of a fast dissolving tablet pharmaceutical formulation in allergic patients. Satisfaction and expectancies. Allergol. Immunopathology. (Madr.,). 2006; 34(3): Ahmed IS, Nafadi MM and Fatahalla FA, Formulation of a fast-dissolving ketoprofen tablet using freeze-drying in blisters 11

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