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  • Anorally disintegrating tabletororally dissolving tablet(ODT) is a drugdosage formavailable for a limited range ofover-the-counter(OTC) andprescriptionmedications. ODTs differ from traditionaltabletsin that they are designed to be dissolved on the tongue rather than swallowed whole. The ODT serves as an alternative dosage form for patients who experiencedysphagia(difficulty in swallowing) or for where compliance is a known issue and therefore an easier dosage form to take ensures that medication is taken. Common among all age groups, dysphagia is observed in about 35% of the general population, as well as up to 60% of the elderly institutionalized populationand 18-22% of all patients in long-term care facilitiesODTs also have a faster onset of effects than tablets or capsules, and have the convenience of a tablet that can be taken without water. During the last decade, ODTs have become available in a variety of therapeutic markets, both OTC and by prescription.

  • Fast Dissolving Tablets (FDTs) or Orally dissolving tablets (ODTs) which disintegrates or dissolves rapidly without water within few seconds in the mouth.

    Products of ODT technologies entered the market in the 1980sThe first ODT form of a drug to get approval from the U.S. FDA was a Zydis ODT formulation of Claritin (loratadine) in December 1996.

    DEFINITION

  • US FDA defined ODTs as A solid dosage form containing medicinal substances or active ingredients which disintegrates rapidly within a few seconds when placed up on tongue

  • Oral route ofadministrationFast DissolveDosage FormA stable, oral dosage formwith the dosing ease of a liquid

  • ClinicalFormulationMarketingPregastric deliveryFaster onsetBetter S&EBioequivalenceLocal delivery

    ComplianceConvenienceStabilityEase of use

    New presentationExtend exclusivityBroader applicationUSP

    ODT

  • First generation ODTsSECOND generation ODTsTHIRD generation ODTsPreparation method Prepared by freeze drying method. Drug suspension along with specific additives was filled into the pockets of press through packing. Wet granulation method Drying the drug and additives after tabletting their wet mass(TUSHIMA 2001). Dry granulation method Dry mass including the drug and saccharides were tabletted.ADVANTAGES RAPID DISINTEGRATION of ODTs Rapid disintegration of ODTs Rapid disintegration of ODTs Less friable then first generation ODTsDISADVANTAGES Handling was difficult because the tablets were very friable Highly sensitive to moisture No Taste masking compounds applied for bitter tasting drugsLow density and hardness LOW HARDNESS OF TABLETS High porosity Low density High porosity Low hardness Low density

  • Good for patients with swallowing difficulties.Good for paediatric complianceConvenient to administer during travelling or working without need of waterThe pre-gastric drug absorption avoids the first-pass metabolism.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 flavors and sweeteners 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.

  • Drug selection criteria

    The ideal characteristics of a drug for oral dispersible tablet include:

    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 50mg.

    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.

  • IMPORTANT CRITERIA FOR EXCIPIENTS USED IN THE FORMULATION OF ODTs:

    It must be able to disintegrate quickly.

    Their individual properties should not affect the ODTs.

    It should not have any interactions with drug and other excipients.

    It should not interfere in the efficacy and organoleptic properties of the product.

    When selecting binder a (single or combination of binders) care must be taken in the final integrity and stability of the product.

    The binders may be in liquid, semi liquid, solid or polymeric mixtures11.

    (Ex: Polyethylene glycol, coca butter, hydrogenated vegetable oils)

  • Disintegrating agents:

    Super disintegrants Commercially available gradesMechanism ofactionSpecial commentCrosslinkedCelluloseCrosscarmelloseAc-Di-Sol,Nymce ZSXPrimellose,Solutab,Vivasol, L-HPCSwells 4-8 folds in < 10 seconds.Swelling andwicking both.Swells in two dimensions.Direct compression or Granulation Starch free.Crosslinked PVPCrosspovidon MKollidonPolyplasdoneSwells very little and returns to original size after compression but act by capillary action.Water insoluble andspongy in nature so get porous tablet.

  • Crosslinked starchExplotabPrimogelSwells 7-12 folds in < 30 seconds.Swells in three dimensionsand high level serve as sustain release matrix.Crosslinked alginicAcidAlginic acid NFRapid swelling in aqueous medium orwicking action.Promote disintegrationin both dry or wet granulation.SoyPolysaccharidesEmcosoyDoes not contain any starch or Sugar. Used inNutritional products.Calcium silicateWicking actionHighly porous,Light weight.

  • Binders : SMCC (Silicified microcrystalline cellulose )SMCC1 SMCC2 SMCC3Starch paste , Natural Gums, Liquid Glucose , etc. ) Flavors:A bitter product - mint, cherry or anise may be used A salty product peach, apricot or liquorice may be used A sour product - raspberry or liquorice may be used An excessively sweet product - vanilla may be used

  • 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 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.

  • Freeze DryingA process in which water is sublimated from the product after freezing. Lyophilization is a pharmaceutical technology which allows drying of heat sensitive drugs and biological at low temperature under conditions that allow removal of water by sublimation. ODTs formed by lyophilization have low mechanical strength, poor stability at higher temperature, and Humidity.

    MouldingIn this method, molded tablets are prepared by using water-soluble ingredients so that the tablets dissolve completely and rapidly. The powder blend is moistened with a hydro-alcoholic solvent and is molded into tablets under pressure lower than that used in conventional tablet compression. The solvent is then removed by air-drying. Molded tablets are very less compact than compressed tablets. These possess porous structure that enhancesdissolution.

  • SublimationThe slow dissolution of the compressed tablet containing even highly water-soluble ingredients is due to the low porosity of the tablets. Inert solid ingredients that volatilize readily (e.g. urea, ammonium carbonate, ammonium bicarbonate,camphor etc.) were added to the other tablet ingredients and the mixture is compressed into tablets. The volatile materials were then removed via sublimation, which generates porous structures. Additionally, several solvents (e.g. cyclohexane, benzene) can be also used as pore forming agents.

  • Zydis TechnologyA Zydis tablet is produced by lyophilizing or freeze-drying the drug in a matrix usually consisting of gelatin.

    The product is very lightweight and fragile, and must be dispensed in a special blis