Oral disintegrating tablets: an overview

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International Journal of
Chemical and Pharmaceutical Sciences
2010, Dec., Vol.1 (2)
Oral Disintegrating Tablets: An Overview
*Velmurugan S and Sundar Vinushitha
KLR Pharmacy College, Palvoncha, Khammam, Andhra Pradesh, India.
*corresponding author: E-mail- [email protected]
ABSTRACT
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
Dysphagia[3] (difficulty in swallowing) is considered as the most widely accepted route because of its convenience of self specific with pediatric, geriatric population administration, compactness and easy along with institutionalized patients ,psychiatric manufacturing.[1-2] But the most evident patients and patients with nausea, vomiting, and drawback of the commonly used oral dosage motion sickness complications.[1] ODTs with forms like tablets and capsules is difficulty in good taste and flavor increase the acceptability swallowing, leading to patients incompliance of bitter drugs by various groups of population. particularly in case of pediatric and geriatric patients[1], but it also applies to people who advantages of dry and liquid formulation. Some are ill in bed and to those active working novel ODT technology allow high drug loading, patients who are busy or traveling, especially have an acceptable taste, offer a pleasant mouth felling, leaving minimal residue in the mouth development of orally disintegrating tablets investigated for their potential in improving (ODTs) has enormously increased as it has bioavaibility of poorly soluble drug through significant impact on the patient compliance. enhancing the dissolution profile of the drug Orally disintegrating tablets are appreciated particularly who have difficulty in called as orodispersible tablets, quick Review Article www.ijcps.com
disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, fast institutionalized patient ( specially for dissolving tablets, rapid dissolving tablets, mentally retarded and psychiatric patients) porous tablets, and rapimelts. However, of all · Pregastric absorption leading to increased bioavaibility/ rapid absorption of drugs from pharmacopoeia (USP) approved these dosage passes down to stomach, also avoids hepatic orodispersible tablet for tablets that disperses readily and within 3 min in mouth before · Convenient for administration to traveling swallowing.[4] Some of super disintegrants patients and busy people who do not have employed in ODTs are discussed in Table 1. United States Food and Drug · Excellent mouths feel property produced by Administration (FDA) defined ODT as “A use of flavours and sweetners help to change the perception of “medication as bitter pill” disintegrates rapidly usually within a matter · Fast disintegration of tablets leads to quick of seconds when placed upon the tongue.” dissolution and rapid absorption which may The disintegration time for ODTs generally ranges from several seconds to about a minute. [5] · ODTs offer all the advantages of solid 2. Drug selection criteria
· Convenience of administration and accurate 4. Desired criteria for ODTs [8-10]
ODT should leave minimal or no residue in At least partially non-ionized at the oral mouth after oral administration, compatible · Have the ability to diffuse and partition · Effective taste masking technologies should · Exhibit low sensitivity to environment · Low dose drugs preferably less than 50 condition such as humidity and temperature. · ODTs should dissolve / disintegrate in the · Short half life and frequent dosing drugs mouth in matter of seconds without water. · Have sufficient mechanical strength and · Drug should have good stability in saliva · The drug and excipients property should not · Very bitter or unacceptable taste and affect the orally disintegrating tablets. · Be portable and without fragility concern. 3. Advantages [7,8]
5. Technologies used for manufacturing of
· Easy to administer to the patient who orally disintegrating tablets
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formulating ODTs including conventional technologies and patented technologies. Table 4 enlisted the various drugs explored 5.1. Conventional Technologies
5.1.1. Freeze drying or lyoplilization
A process, in which water is thereby enhancing the dissolution characteristic sublimated from the product after freezing, is of the formulation. The entire freeze drying called freeze drying. Freeze- dried forms process is done at nonelevated temperature to eliminate adverse thermal effects that may available solid products. The lyophilization affect drug stability. The major disadvantages of processes imparts glossy amorphous lyophilization technique are that it is expensive structure to the bulking agent and some times conventional packaging unsuitable for these Table 1: Superdisintegrants employed in
products and poor stability under stressed conditions and their limited ability to accommodate adequate concentration of Mechanism
disintegrants
of Action
5.1.2. Direct compression
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 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, disruptive change in the tablet. Effective 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 Review Article www.ijcps.com
are particle size distribution, contact angle, can be added to the formulation, but then the pore size distribution and water absorption rate of tablet solubility usually decreases.[16,17] capacity. Studies revealed that the water 5.1.4. Mass extrusion
insoluble superdisintegrants like sodium starch glycolate and Croscarmellose sodium show better disintegration property than the active blend using the solvent mixture of water slightly water soluble agents like soluble polyethylene glycol, using methanol and Crospovidone, since they do not have a expulsion of softened mass through the extruder tendency to swell. Superdisintegrants that or syringe to get a cylinder shaped extrude tend to swell show slight retardation of the which are finally cut into even segments using disintegration property due to formation of heated blade to form tablets. This process can viscous barrier. There is no particular upper also be used to coat granules of bitter drugs to limit regarding the amount of mask their taste. Mass extrusion was the superdisintegrant as long as the mechanical technique used for preparing taste masked properties of the tablet are compatible with granules. The tablet was prepared with different its intended use. The superdisintegrant may super disintegrate e.g. sodium starch glycolate, be used alone or in combination with other 5.1.3. Molding
5.1.5. Melt granulation
from soluble ingredients, by compressing a powder mixture which is moistened with a efficiently agglomerated by a melt able binder. solvent, into mould plates to form a wetted The advantage of this technique compared to a conventional granulation is that no water or prepared directly from a molten matrix, in organic solvents is needed. For accomplishing which the drug is dissolved or dispersed or this process, high shear mixers are utilized, where the product temperature is raised above solution or suspension at a standard pressure. the melting point of binder by a heating jacket Usually molded tablets are compressed at a or by the heat of friction generated by impeller lower pressure than are conventional are blades. This approach to prepare FDT with conventional tablets, and posses a porous sufficient mechanical integrity, involves the use structure that hastens dissolution. To of a hydrophilic waxy binder (Superpolystate, improve the dissolution rate, the powder PEG-6-stearate). Superpolystate is a waxy blend usually has to be passed through a very material with a melting point of 33–37°C and a fine screen. Tablet produced by molding are HLB value of 9. So it will not only act as a solid dispersion. Molded tablets disintegrate binder and increase the physical resistance of tablets but will also help the disintegration of because the dispersion matrix is in general the tablets as it melts in the mouth and made from water soluble sugars. The active solublises rapidly leaving no residues.[20] 5.1.6. Phase transistion process
through the mucosal lining of the mouth. Kuno et al proposed a novel method to Unfortunately, moulded tablets typically do prepare ODTs with sufficient hardness by involving the phase transition of sugar alcohol. Erosion and breakage of the moulded tablets often occurs during tablet handling and when compressing powder containing erythritol blister pockets are opened. Hardness agents Review Article www.ijcps.com
(melting point: 122 °C) and xylitol (melting mouth the freeze dried structure disintegrates point: 93 - 95 °C), and then heating at about instantaneously and does not require water for 93 °C for 15 min. After heating, the median swallowing. Polymers such as gelatin, dextran pore size of the tablets was increased and or are incorporated to impart strength during tablet hardness was also increased. Heating handling. Mannitol or sorbitols are incorporated, to obtain crystallanity, elegance and hardness. particles leading to sufficient hardness of Flocculating agents (e.g, xanthan gum and tablets which was otherwise lacking owing to acacia) to provide uniform dispersion of drug particles; preservatives(e.g., parabens) to 5.1.7. Sublimation
prevent microbial growth; permeation enhancers(e.g., sodium lauryl sulphate) to The slow dissolution of the improve transmucosal permeability; pH compressed tablet containing even highly adjusters(e.g, citric acid) to optimize chemical water soluble ingredients is due to the fact stability; flavours and sweetners to improve that the low porosity of the tablets reduces manufacturing process to ensure production of the matrix. When inert volatile solid ingredie porous units to achieve rapid disintegration. Gums prevent the sedimentation of dispersed carbonate, benzoic acid, camphor, hexameth particles in manufacturing process. Collapse ylene tetramine, naphthalene, phthalic protectants like gelatin prevents the shrinkage of anhydride, urea and urethane were added to Zydis units during freeze-drying process or on along with other tablet excipients and the long term storage. The product is very light blend was compressed in to a table, which weight and fragile, and must be dispensed in a sublimation resulting in highly porous structures. Sublimation has been used to 5.2.2. Orasolv technology
compressed tablets exhibit good mechanical dissolving/disintegrating dosage form. In this strength and have high porosity system active medicament is taste masked, (approximately 30%) rapidly dissolved contains disintegrating agent. The disintegration of ODT in the mouth is cause by the action of 5.2. PATENTED TECHNOLOGIES
an effervescent agent, activated by saliva. The amount of effervescent agent is in general about 5.2.1. Zydis technology
20-25% of the total weight of the tablet. The Zydis was the first marketed widely used effervescent disintegration pair technology developed by R.P.Scherer,Inc. usually include an acid source (citric, tartaric, malic, fumeric, adipic and succinics ) and a tablets .Zydis, the best known of the fast carbonate source (sodium bicarbonate, sodium dissolving/disintegrating tablet preparations carbonate, potassium bicarbonate and potassium was the first marketed new technology tablet. The tablet dissolves in the mouth within seconds after placement on the tongue.Zydis maintain the integrity of the coating.The major formulation is a unique freeze dried tablet in disadvantage of the OraSolv formulations is its mechanical strength. For that reason, Cima developed a special handling and packaging components, a saccharide e.g. mannitol and a system for OraSolv. Manufacturing requires a polymer. When Zydis units are kept in the controlled environment at low relative humidity Review Article www.ijcps.com
and protection of the final tablets with 5.2.5. Cotton candy technology
This process is so named as it utilizes an 5.2.3. Durasolv technology
inimitable spinning mechanism to produce floss Durasolv is CIMA’s second like crystalline structure, which mimics cotton generation fast dissolving or disintegrating candy. The cotton candy process also known as tablet formulation to produce stronger tablets the candy floss process. A mouth dissolving tablet is formed using candy floss or shear form bottles. Durasolv has much higher matrix.It involves the formation of matrix of mechanical strength due to use of the higher polysaccharides or saccharides by simultaneous compaction pressure during tabletting. One action of flash melting and spinning. The matrix formed is partially recrystallised to have technology is not compatible with larger improved flow properties and compressability. doses of active ingredients, because the This candy floss matrix is then milled and formulation is subjected to high pressure blended with active ingredients, excipients and during compaction. The drug powder coating subsequently compressed to ODT. This process can accommodate larger drug doses and offer compaction, exposing the bitter tasting drugs improved mechanical strength. However, high to the patient taste buds.So This technology process temperature limits the use of this is good for tablets having low amount of 5.2.6. Oraquick technology
5.2.4. Wow tab technology
The WOW in the WOWTAB disintegrating tablets formulation utilizes a signifies the tablet is to be given without patented taste masking technology. This taste water. This technology utilizes sugar and masking process does not utilize solvents of any sugar-like excipients. The two different types kind, so leads to faster and more efficient production. During processing low-heat is tablet formulation with adequate hardness produced so this technique is suitable for heat and fast dissolution rate. The two different sensitive drugs. KV pharmaceuticals also claims saccharides are those with high moldability that the matrix that surrounds and protects the like maltose, mannitol, sorbitol, and drug powder in microencapsulated particle is oligosaccharides.(good binding property) and more pliable.This technique gives tablets with good taste masking and quick dissolution in mannitol, xylitol (rapid dissolution). Tablets 5.2.7. Nanocrystal technology
sufficient hardness to maintain the physical characteristics of the dosage form during technology provides for: Pharmacokinetic production until it comes in contact with benefits of orally administered nanoparticles moisture such as saliva in mouth. Due to the (<2 microns) in the form of a rapidly significant hardness the WOWTAB disintegrating tablet matrix.Nano Crystal formulation is more stable to the colloidal dispersions of drug substance are combined with water-soluble GRAS (Generally Erythritol was found to be the best sugar for Regarded As Safe) ingredients, filled into blisters, and lyophilized. This method avoids disintegration which is unaffected by tablet manufacturing process such as granulation, Review Article www.ijcps.com
advantages for highly potent and hazardous a standard tablet press with stock tooling. The drugs.For fast dissolving tablets, Elans manufacture process can be carried out under normal temperature and humidity conditions. The tablets can be packaged in blister packs or activity and final product characteristics. Decreasing particle size increases the surface 5.2.10. Frosta technology
area,which leads to an increase dissolution rate. [27] concept of Frosta technology is compressing 5.2.8. Shearform technology
highly plastic granules at low pressure to produce strong tablets with high porosity. The matrix, ‘Floss’ is prepared. Feedstock highly plastic granules comprise three classes of prepared with a sugar carrier is subjected to components: a porous and plastic material, a flash heat processing. In this process, sugar is water penetration enhancer, and a binder. The simultaneously subjected to centrifugal force process involves mixing the porous plastic and to a temperature gradient, which causes material with water penetration enhancer the temperature of the mass to rise and hence followed by granulating with binder. The technology can be used for almost any drugs permitting part of it to move with respect of including aspirin, loratidine, caffeine, and folic the mass. This is followed by its exit through acid, vitamins and dietary supplements. The the spinning head that flings the floss under highly plastic granule approach produces fast centrifugal force and draws into long and melting pharmaceutical tablets with excellent thin floss fibres, which are usually hardness and fast disintegration time ranging amorphous in nature.the floss so produced is from several seconds to 30 seconds, depending further chopped and recrystallised to provide a uniform flow, thus facilitate blending. Then 6. EVALUATION OF ODTs
the recrystallised matrix, active drug and other excipients are blended together and finally compressed into tablets. Active drug mentioned in the Pharmacopoeias need to be and other excipients may be blended with the assessed, along with some special tests are floss before recrystallising it. The tablets 6.1. Hardness
porous in nature and offer very pleasant A significant strength of ODT is difficult mouth feel due to rapid solubilisation of to achieve due to the specialized processes and ingredients used in the manufacturing. The limit 5.2.9. Pharmaburst technology
of hardness for the ODT is usually kept in a lower range to facilitate early disintegration in by SPI pharma. Pharmaburst technology uses the mouth. The hardness of the tablet may be off the shelf coprocessed excipients to create measured using conventional hardness test. an ODT that, depending on the type of active 6.2. Friability
ingredients and loading, dissolves within 30- To achieve % friability within limits for an ODT is a challenge for a formulator since all required in a formulation depends on the active ingredients in the tablet. The process responsible for increasing the % friability values. involves a dry blend of a drug, flavor and Thus, it is necessary that this parameter should lubricant that are compressed into a tablet on Review Article www.ijcps.com
be evaluated and the results are within bound implies a quicker disintegration of the tablet. The wetting time of the tablets can be measured Table .2 ODT products available in
by using the simple procedure.[29] Five circular international market
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 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 6.4. Moisture uptake studies
be conducted to assess the stability of the formulation. Ten tablets from each formulation were kept in a dessicator over calcium chloride at 370C 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 6.5. Disintegration test
generally <1min and actual the disintegration time that patients can experience ranges from 5 6.3. Wetting time and water absorption
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. related to with the contact angle. Wetting The disintegration test for ODT should mimic disintegration in mouth with in salivary contents. parameter, which needs to be assessed to give an insight into the disintegration properties of the tablet. Lower wetting time Review Article www.ijcps.com
6.6. Dissolution test
methods for ODT is comparable to approach 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 trapped on the inside top of the basket at the indicated that USP 2 paddle apparatus is spindle where little or no effective stirring occurs, yielding irreproducible results in dissolution test of ODT tablets, where a paddle speed of 50 rpm is commonly used. Table .4: Drugs explored for orally
Typically the dissolution of ODTs is very disintegrating tablet [31]
fast when using USP monograph conditions. Hence slower paddle speeds may be utilized Category Drugs
Category Drugs
to obtain a comparative profile. Large tablets Analgesics
and Anti-
Epileptics
inflammat
containing relatively dense particles may ory Agents
produce a mound in the dissolution vessel, paddle speeds. These two situations expand the suitable range of stirring to 25-75 rpm. certain applications for ODT but is used less frequently due to specific physical properties Table 3: ODT products in Indian market:
bacterial
Hypertensi
ve Agents:
Brand Name
Ingredients
Arrhythm
Neoplastic
ic Agents
Immunosu
ppressants
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bacterial
Inotropic
Blockers :
Protozoal
Malarials:
coagulants
Diuretics:
7. Patient counseling points for ODT
Anxiolytic,
Sedatives,
Parkinsoni
Hypnotics
an Agents:
advancement in novel dosage form, thus have Neurolepti
opportunity to counsel the patient for effective treatment. Educating the patients about ODT Anti-Gout
can avoid any confusion and misunderstanding Counseling points to the patients include: Histamine
Regulatin
g Agents:
Receptor
Antagonist
effervescent tablets, pharmacist need to be clearly told about the different between durasolv use slight effervescence, patients may experience a pleasant tingling effect Nitrates
And Other
Migraine
· Patients with dryness of mouth or with Corticoster
analgesics
efficiently but most technologies of ODT Intestinal
Muscarinic
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8. CONCLUSION
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