Oral Disintegrating Tablets 2015

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  • 7/26/2019 Oral Disintegrating Tablets 2015



    Agus Siswanto

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    Oral Disintegrating Tablets

    A solid dosage form containing medicinalsubstance or active ingredient whichdisintegrates rapidly usually within a matter of

    seconds when placed upon the tongue (FDA) Uncoated tablets intended to be placed in the

    mouth where they disperse rapidly beforebeing swallowed and as tablets which should

    disintegrate within 3 min (EuropeanPharmacopoeia )

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    Drug selection criteria

    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 areunsuitable for ODT

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    Choice of drug candidate

    No bitter taste

    Good stability in water and saliva

    Dose should be low as possible

    Unsuitable drug candidate for orally disintegratingtablet should include:

    Short half-life and frequent dosing Drug having very bitter taste

    Required controlled or sustained release

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    Advantages of ODT

    Improved patient compliance Rapid onset of action and may offer an improved


    Useful for pediatric, geriatric and psychiatric patients

    Suitable during traveling where water is may not beavailable

    No specific packaging required, can be packaged inpush through blisters

    Smooth mouth feel and pleasant taste

    Conventional manufacturing equipment

    Cost effective

    Good chemical stability as conventional oral soliddosage form

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    Characteristics of an Ideal ODT

    Utilizes cost effective production method

    Require no water for oral administration

    Dissolve / disperse/ disintegrate in mouth in a

    matter of seconds Have a pleasing mouth feel and taste masking.

    Less friable and have sufficient hardness

    Leave minimal or no residue in mouth after

    administration Manufacturing using conventional manufacturing


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    Basic approaches to develop Oral Disintegrating Tablets

    porous structure

    highly water-soluble


    appropriate disintegrating


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    Techniques in preparation of ODT

    1. Freeze drying or


    2. Spray Drying

    3. Direct Compression

    4. Sublimation

    5. Cotton Candy Process6. Mass Extrusion

    7. Moulding

    8. Nanonization

    9. Fast Dissolving Films10. Phase transition


    11. Melt granulation

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    Freeze drying or Lyophilization

    Lyophilization means drying at low temperature undercondition that involves the removal of water bysublimation

    Drug in a water soluble matrix which is then freeze

    dried to give highly porous structure The tablets prepared by lyophilization disintegrate

    rapidly in less than 5 seconds due to quick penetrationof saliva in pores when placed in the oral cavity

    Lyophilization is useful for heat sensitive drugs i.e.thermo-labile substances

    Ex. Loratidine (Claritin Reditab and Dimetapp QuickDissolve)

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    10/45Freeze drying or Lyophilization

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    Spray drying

    Spray drying can produce highly porous and finepowders that dissolve rapidly

    This technique is based on a particulate support

    matrix, which is prepared by spray drying anaqueous composition containing support matrixand other components to form a highly porousand fine powder

    This then mixed with active Ingredients andcompressed into tablets

    Ex. Hyoscyamine Sulfate ODT

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    Spray drying

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    Direct compression

    This is most popular technique because of its easyimplementation and cost-effectiveness Direct compression represents the simplest and most cost

    effective tablet manufacturing technique

    This technique can now be applied to preparation ofODT because of the availability of improved excipientsespecially superdisintegrants and sugar basedexcipients

    The basic principle involves addition of disintegrantsand/or water soluble excipients and/or effervescentagents

    Superdisintegrants in optimum concentration (about 2-5%) are mostly used so as to achieve rapid

    disintegration along with the good mouth feel

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    (a) Superdisintegrants

    In many orally disintegrating tablettechnologies based on direct compression, theaddition of superdisintegrants principally

    affects the rate of disintegration and hencethe dissolution

    The presence of other formulation ingredientssuch as water-soluble excipients andeffervescent agents further hastens theprocess of disintegration

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    Mechanism of Superdisintegrants


    Porosity and capillary action (Wicking)

    Due to disintegrating particle/particlerepulsive forces

    Due to deformation

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    1. Swelling

    Perhaps the most widely accepted general mechanismof action for tablet disintegration is swelling

    Tablets with high porosity show poor disintegrationdue to lack of adequate swelling force

    On the other hand, sufficient swelling force is exertedin the tablet with low porosity

    It is worthwhile to note that if the packing fraction isvery high, fluid is unable to penetrate in the tablet anddisintegration is again slows down

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    2. Porosity and capillary action


    Disintegration by capillary action is always the firststep.

    When we put the tablet into suitable aqueous medium,the medium penetrates into the tablet and replaces

    the air adsorbed on the particles, which weakens theintermolecular bond and breaks the tablet into fineparticles.

    Water uptake by tablet depends upon hydrophilicity ofthe drug /excipient and on tableting conditions.

    For these types of disintegrants maintenance of porousstructure and low interfacial tension towards aqueousfluid is necessary which helps in disintegration bycreating a hydrophilic network around the drug


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    3 D t di i t ti

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    3. Due to disintegrating

    particle/particle repulsive forces

    Another mechanism of disintegratn attempts to explainthe swelling of tablet made with nonswellabledisintegrants.

    Guyot-Hermann has proposed a particle repulsiontheory based on the observation that nonswellingparticle also cause disintegration of tablets.

    The electric repulsive forces between particles are themechanism of disintegration and water is required for


    Researchers found that repulsion is secondary towicking.

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    4. Due to deformation

    During tablet compression, disintegranted particles getdeformed and these deformed particles get into theirnormal structure when they come in contact withaqueous media or water.

    Occasionally, the swelling capacity of starch wasimproved when granules were extensively deformedduring compression.

    This increase in size of the deformed particles produces

    a break up of the tablet.

    This may be a mechanism of starch and has onlyrecently begun to be studied.

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    (b) Sugar Based Excipients

    This is another approach to manufacture ODTby direct compression

    The use of sugar based excipients especially

    bulking agents like dextrose, fructose, isomalt,lactilol, maltilol, maltose, mannitol, sorbitol,starch hydrolysate, polydextrose and xylitol,which display high aqueous solubility andsweetness, and hence impart taste maskingproperty and a pleasing mouthfeel

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    Mizumito et al have classified sugar-based

    excipients into two types on the basis ofmolding and dissolution rate

    Type 1 saccharides

    exhibit low mouldability but high dissolution rate

    lactose and mannitol

    Type 2 saccharides

    exhibit high mouldability and low dissolution rate

    maltose and maltilol

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    This technique is based on the use of volatileingredients (e.g. camphor, ammoniumbicarbonate, naphthalene, urea, urethane

    etc.) to other tablet excipients and themixture is then compressed into tablets

    Entrapped volatile material is then removedvia sublimation, which leads to formation of aporous structure

    Ex. Phloroglucinol Hydrate (Spasfon Lyoc)

    S I l d i bli i

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    Steps Involved in sublimation

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    Cotton candy process

    Involves the formation of matrix of

    polysaccharides by simultaneous action of

    flash melting and spinning

    This candy floss matrix is then milled andblended with active ingredients and

    excipients after re-crystallization and

    subsequently compressed to FDT

    Characteristics: It can accommodate high doses

    of drug and offers improved mechanical strength

    Ex- Tramadol HCl (Relivia Flash dose)

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    Involves softening the active blend using thesolvent mixture of water soluble polyethyleneglycol, methanol and expulsion of softenedmass through the extruder or syringe to get acylindrical shape of the product into evensegments using heated blade to form tablets

    Characteristics: The dried product can be used

    to coat granules of bitter tasting drugs andthereby masking their bitter taste

    Ex. Zolmitriptan (Zolmig ZMT)

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    water-soluble ingredients with a hydro-alcoholic solvent is used and is moldedinto tablets under pressure lower than that

    used in conventional tablet compression Characteristics: Molded tablets are very

    less compact than compressed tabletporous structure that enhances

    disintegration/ dissolution and finallyabsorption increased

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    Involves size reduction of drug to nanosize bymilling the drug using a proprietary wet-millingtechnique

    The Nanocrystals of the drug are stabilized againstagglomeration by surface adsorption on selectedstabilizers, which are then incorporated into FDTs

    Characteristics: It is used for poorly water soluble drugs

    It leads to higher bioavailability and reduction in dose,cost effective manufacturing process, conventionalpackaging due to exceptional durability and wide rangeof doses (up to 200 mg of drug per unit)

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    Ing. and Tech. Used for Formulating FDT:

    Drug Disint.Agent


    Other form. Ing. Tech. used Disint. Time

    NSAIDS Crospovidon








    stearate, stearic


    Wet granulation &



    50 sec

    (for 125



    granulesCross linked


    Lemon flavor,



    Freeze drying< 30 sec



    Avicel ph




    Moulding, Direct

    Compression31-37 sec

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    Preformulation studies of ODT

    Powder flow properties

    Bulk Density (Db)

    Tapped Density (Dt) Angle of Repose

    Carrs index (or) % compressibility

    Hausner ratio

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    Evaluation test for ODT

    General Appearance Hardness

    Drug Content

    In-Vitro drug release

    Modified disintegrationtest

    Moisture uptake study

    Weight variation Friability (F)

    Wetting time & Water

    absorption Ratio

    Powder X-ray diffraction In-vitro dispersion time

    Stability study

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    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 quickerdisintegration of the tablet.

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    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 ofthe tissue paper. The time required for water to reach

    upper surface of the tablet is noted as the wetting time.

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    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


    R = 100 (Wa-Wb) / Wb

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    Disintegration test

    The time for disintegration of ODTs is generally

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    Modif ied disintegration test

    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 time for ODT needs to be modified as

    disintegration is required without water, thus the test shouldmimic disintegration in salivary contents.

    For this purpose, a petridish (10 cm diameter) was filled with

    10 ml of water.

    The tablet was carefully put in the center of petridish and thetime for the tablet to completely disintegrate into fine particles

    was noted.

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    Dissolution test

    Commonly the drugs may have dissolution conditions asin 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.

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    Patient counseling points for ODT

    Patients may mistake ODT for effervescent tablets,

    pharmacist need to be clearly told about the different

    between them

    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 dispensequickly 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

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    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 alsofor geriatric patients who have lost their teeth permanently.

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