Review on Taste msking Approches & Evalution


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Review on Taste msking Approches & Evalution

  1. 1. A Seminar onReview On: Taste MaskingApproaches & Evalution. Presented by Sagar B. Thoke M. Pharm IInd Semester [Dept. of Pharmaceutics] Guided by Prof . Y. P. Sharma
  2. 2. Contents :- The human tongue- Anatomy & Physiology Problems arise in taste masking Ideal taste masking process and formulation properties Factors consideration during the taste masking Approaches to Unpleasant Taste Inhibition Evaluation of Taste Masking Effect References 5/17/2012 2
  3. 3.  The human tongue :- Organ for taste, help in speech, swallowing. Anatomy & Physiology of the Tongue :- Tongue Muscles  Intrinsic muscles  Extrinsic muscles Vasculature receives blood supply primarily from the lingual artery, which drain into internal jugular vein. Length-from the oropharynx to the tip is 10 cm (4 in). Tongue physiology The chemicals bind their particular receptors and initiate signaling that travels through the nerves to the brain, where they are interpreted. 5/17/2012 3
  4. 4. Fig. Taste Points in Tongue Fig. Physiology of Taste Bud Taste Chemical Salty Ions (ex: sodium) Sweet Sugars, ketones, aldehydes, some amino acid Sour Acidic compounds Bitter Not yet known, possible link to toxicityUmami (savory)* L-glutamate/glutamic acid  Fifth taste bud type discovered in 2002. 5/17/2012 4
  5. 5. Taste Signaling PathwaysTaste transduction begins with the interaction of a tastant (eg.medicine or food) with taste receptor cells in the taste buds8 (Fig ).The tastant binds with G-Protein coupled receptors (GPCRS) in thecells triggering the release the release of G-Protein calledGustducin. 5/17/2012 5
  6. 6. Taste Blocking MechanismTaste sensation begins when Gustducinactivates the effector enzymesphosphodiesterase IA (PDE) or phospholipaseC beta-2(PLC).The effector enzyme then changes theintracellular level of second messenger such ascyclic adenosine monophosphate (cAMP),Inositol, 1, 4, 5- triphosphate (IP3) anddiacylglycerol (DAG).The second messengers activate calcium ionchannel inside the cell and sodium, potassiumand calcium channel on extra cellularmembrane.Ionization depolarizes the cell causing releaseof neurotransmitters that send nerve impulsesto the brain that carries the signal of bitter tasteand taste blockers work by interfering withtaste transduction. 5/17/2012 6
  7. 7. Taste refers to a perception arising from the stimulation of tastebuds.Undesirable taste- problems in formulation & patientcompliance.Children, older persons, trouble swallowing tablets or capsules. chewable solid form (sublingual or buccal tablets), liquid form or ODT. Taste of Ciprofloxacin mask by sodium saccharin in ODT. Taste masking- reduction of an undesirable taste. Problems arise in taste masking :-  Inadequate taste masking  Coating- imperfections, if present, reduce the efficiency. 5/17/2012 7
  8. 8.  Ideal taste masking process & formulation properties :- 1) Involve least number of equipments and processing steps. 2) Require minimum number of excipients for an optimum formulation. 3) No adverse effect on drug bioavailability. 4) Least manufacturing cost. 5) Can be carried out at room temperature. 6) Require excipients that are economical, easily available with high margin of safety. 7) Rapid and easy to prepare. 5/17/2012 8
  9. 9.  Factors consideration during the taste masking :- 1) Extent of the bitter taste of the API. 2) Required dose load. 3) Drug particulate shape and size distribution. 4) Drug solubility and ionic characteristics. 5) Required disintegration & dissolution rate of finished product. 6) Desired bioavailability. 7) Desired release profile. 8) Required dosage form. 5/17/2012 9
  10. 10. Taste masking patents and patent applications are contributed from  Asia-49.34%  North America- 41.45% of which 62.67% were filed in USA and  Europe- 9.30% 5/17/2012 10
  11. 11. Taste masking technology filed in the period of year 1997 to 2007.(% contribution of each different taste masking technologiesCalculated.) 5/17/2012 11
  12. 12. Fig. Taste Masking Technologies uses in liquid and solid dosage forms 5/17/2012 12
  13. 13.  Approaches to Unpleasant Taste Inhibition :-1. Taste masking with flavors, sweeteners, and amino acids2. Taste Masking by Inclusion Complexation3. Taste Masking by Ion-Exchange Resins (IERs)4. Taste Masking by Microencapsulation5. Solid dispersion6. Mass extrusions7. Multiple Emulsions8. Wax Embedding of Drug9. Development of Liposome10. Taste masking by adsorption11.Taste masking by Prodrug approach 5/17/2012 13
  14. 14. 12. Taste Masking with Lipophilic Vehicles like lipids andlecithins13. Taste Suppressants and Potentiators14. Granulation15. pH Modifiers16. Freeze Drying Process17. Viscosity Modifications18. Salt Preparation19. Taste masking by gelation 5/17/2012 14
  15. 15. 1. Taste Masking with Sweeteners and Flavours 1. Flavors Natural Flavors Synthetic Flavors  Juices - Raspberry  Alcoholic solutions  Extracts - Liquorices  Aqueous solutions  Spirits - Lemon & Orange  Powders  Syrups – Blackcurrant  Tinctures -Ginger  Aromatic waters - Anise & Cinnamon  Aromatic Oils – Peppermint & Lemon.Natural Vs Synthetic Cheaper More readily available Less variable in chemical composition More stable 5/17/2012 15
  16. 16. Basis of Choosing a Flavor  Complementary to existing flavor of the drug  Known popularity of particular flavors  Age of patients  AllergyFlavoring agents for taste masking Basic Taste Masking agents Salt Butterscotch, maple, apricot, peach, vanilla, wintergreen mint. Bitter Wild cherry, walnut, chocolate, mint, anise. Sweet Vanilla, fruit and berry. Sour Citrus flavor, licorice, root beer, raspberry.2. Sweetners  Complement flavors associated with sweetness  Soothing effect on the membranes of the throat 5/17/2012 16
  17. 17. Natural Artificial Nutritive Polyols NovelSweetener Sweetener Sweeteners SweetenersSucrose, Saccharin, Sucrose, Mannitol, Trehalose,Glucose, Saccharin Fructose and Sorbitol, TagatoseFructose Sodium Glucose Xylitol,Sorbitol, Aspartame Erythritol,Mannitol, Maltitol.GlycerolHoney,LiquoriceTaste masking of water soluble bitter drugs, with a high dose, isdifficult to achieve by using sweeteners alone. 5/17/2012 17
  18. 18. List of FDA approved Non-Nutritive sweeteners Sweeteners Sweetness factor, Sucrose=1 Aspartame 180-200 Sucralose 600 Acesulfame K 200 Neotame 7,000-13,000 Saccharin 3003. Amino Acids and Protein Hydrolysates combining amino acids or their salts with bitter drugs, reduce the bitterness. Amino acids- sarcosine, alanine, taurine, glutamic acid, and glycine. Ampicillin granules with glycine and mixing them with additional quantity of glycine, sweeteners, flavors. 5/17/2012 18
  19. 19. 2. Taste Masking by Inclusion ComplexationDrug molecule fits into the cavity of a complexing agent, i.e. thehost molecule, forming a stable complex.Vander Walls forces are mainly involved in inclusion complexes.low stability constant lead to a rapid release of free drugHydrophobic drugs form complex by replacing „inclusion water‟while easily migrating (hydrophilic, well soluble) drugs formcomplex, assuming replacement of „crystal water‟.β-cyclodextrin- sweet, non-toxic, cyclic oligosaccharide obtainedfrom starch.  Decreasing its oral solubility on ingestion or  Decreasing the amount of drug particles exposed to taste buds Suitable only for low dose drugs. 5/17/2012 19
  20. 20. 3. Taste Masking by Ion-Exchange Resins (IERs) High molecular weight polymers With cationic and anionic functional groups Ability to exchange counter-ions within aqueous solutions surrounding them. small (1-2 mm diameter) beads with pores structure.ClassificationA. Cation Exchange Resina) strong cation exchanger contains sulphuric acid sitesb) Weak cation exchangers based on carboxylic acid moieties.B. Anion Exchange Resina) strong anion exchange resins have quaternary amine ionic sites attached to the matrix,b) weak anion exchanger has predominantly tertiary amine substituents. 5/17/2012 20
  21. 21.  Drugs are attached to the oppositely charged resin substrate, by weak ionic bonding form insoluble complex. which does not dissociates the drug-resin complex at salivary pH conditions.Drug release depends on- properties of the resin and the ionic environment within the GIT.Cation exchange or weak anion exchange resinsexamples of IER – drug complex Resin Medicament Name Functionality Polymer backboneAmberliteTM Weak acid Crosslinked Dextromethorphan,IRP64 COO- polyacrylic DimenhydrinateAmberliteTM Strong acid Styrene-Divinyl RanitidineIRP69 SO3- Benzene 5/17/2012 21
  22. 22. AmberliteTM Weak acid Crosslinked Talampacillin-HCl,IRP88 COO- polyacrylic ParoxetineIndion 204 Weak acid Crosslinked Norfloxacin, COO- polyacrylic OfloxacinIndion 214 Weak acid Crosslinked Azithromycin COO- PolyacrylicIndion 234 Weak acid Crosslinked Ciprofloxacin, COO- Polyacrylic Chloroquin phosphateKyron T-104 Weak acid Crosslinked Cefpodoxime, COO- polyacrylic proxetilKyron T-114 Weak acid Crosslinked Ofloxacin COO- PolyacrylicKyron T-134 Weak acid Crosslinked Metronidazole COO- polyacrylic 5/17/2012 22
  23. 23. 4. Taste Masking by Microencapsulation process by which very tiny droplets or particles of liquid or solid material are surrounded or coated with a film or polymeric material. Coating created a physical barrier between the drug and the taste buds. Reduce its solubility in saliva and thus mask taste. Factors to be consider  completely mask the taste of a bitter drug, &  not adversely affecting the intended drug release profile. Polymers used for coating- water insoluble polymers- cellulose ethers, cellulose ester, polyvinyl acetate water soluble polymers- cellulose acetate butyrate, PVP, hydroxyethyl cellulose 5/17/2012 23
  24. 24. 5. Solid Dispersionsas dispersion of one or more active ingredients in an inert carrier ormatrix at solid stateprepared by melting (fusion) solvent or melting solvent method.Amine or amido group of dimenhydrinate can have a physical andchemical interaction with the carboxylic acid and esters groups.Natural copolymers- shellac, zein and cellulose acetate phthalatehydrophobic polymers and long chain fatty acids.enteric polymers like derivatives of acrylic acid polymers andphthalate are good choicesrequires a higher concentration of excipients compared to othertechniques7. Multiple EmulsionsBitter taste of chloroquine was masked in o/w/o and w/o/wemulsion system. 5/17/2012 24
  25. 25. 9. Development of Liposome Masking the unpleasant taste of therapeutic agent by entraping them into liposome.Incorporation of drug into liposomes prepared with eggphosphatidyl choline masked the bitter taste of antimalarial,Chloroquine phosphate in HEPES (N-2- hydroxyethylpiperzine-N-2 ethane sulfonic acid) buffer at pH 7.2.10. Taste masking by adsorptionAdsorbate of bitter tasting drug less saliva soluble.Preparing a solution of the drug and mix with an insoluble powderthat will adsorb the drug, remove the solvent, dry it.Veegum, bentonite, silica gel and silicates used as adsorbate.Ranitidine with a synthetic cation exchange resin adsprbate.Loperamide and phenyl propanolamine adsorbed on magnesiumaluminium silicates (Veegum F) form taste masked suspension. 5/17/2012 25
  26. 26. 11. Taste masking by Prodrug approach Prodrug - chemically modified inert drug precursor which upon biotransformation liberates pharmacologically active parent compound. reducing solubility, and thereby improving taste. Bitterness of a molecule due to the efficiency of taste receptor substrate adsorption reaction, which is related to the molecular geometry of the substrate. By derivative formation, the geometry is altered, affecting the adsorption constant. changing the molecular configuration of the parent molecule change Magnitude of a bitter taste. Nalbuphine HCL, naltrexone, naloxone, oxymorphone HCL, butorphanonol, and levallorphan tasteless prodrug for buccal administration. 5/17/2012 26
  27. 27. Parent Drug ProdrugErythromyci Erythromycin PropionateClindamycin Clindamycin palmitate esterChloramphenicol Chloramphenicol palmitate esterMorphine N-oxide derivatives of all MorphineTriamcinolone Triamcinolone diacetate ester18. Salt PreparationAdding alkaline metal bicarbonate (sodium bicarbonate) masks theunpleasant taste of water -soluble ibuprofen salts in aqueoussolution.Penicillin prepared as N, N-di benzyl ethylene diaminediacetatesalts or N, N-bis (deyhdroabiety) ethylene diamine salts istasteless. 5/17/2012 27
  28. 28. 13. Taste Suppressants and Potentiators Linguagen’s bitter blockers (e.g. adenosine monophos-phate) compete with bitter substances to bind with the G-protein coupled(GPCR) receptor sites. Hydrophobic nature of drug contributes to binding and inter- action with the receptor sites. Suppressants Lipoproteins are universal bitter taste blockers. lipoproteins composed of phosphatidic acid and β-lactoglobulin inhibit the taste nerve responses to the only bitter substances. Phospholipid (BMI-60) Neohesperidine phospholipids- interact chemically with the taste receptors. Cooling and warming agents- extreme sensations to overpower the bitter taste and confuse the brain. 5/17/2012 28
  29. 29. Thymol taste mask by mixture of cooling (e.g. eucalyptol) andwarming agents (e.g. methyl salicylate).Potentiators- increase the perception of the taste of sweeteners. Potentiators Sweeteners Thaumatine, neohesperidine sodium or calcium saccharinates, dihydrochalcone (NHDC) and saccharin, aspartyl-pheny- glycyrrhizin lalanine, acesulfame, cyclamates, and stevioside.Bromhexine- Thaumatine with sugar alcohols mask taste.Bitter taste blockers- Hydroxy flavanones, adenosinemonophosphate and γ-amino butanoic acid.Desensitizing agents- desensitize the taste buds by interferingwith taste transduction.e.g. phenols, sodium phenolates 5/17/2012 29
  30. 30. 15. pH ModifiersThe enteric polymers (eudragit L) solubilize at pH beyond pH 5.5& pH of saliva 5.8. possibility of drug partially leached.pH Modifying agents- generating a specific pHmicroenvironment & facilitate in situ precipitation of bitter drugin saliva, reducing taste sensation.L-arginine maintains alkaline pH of the vehicle to promoteprecipitation of des-quinolone in saliva.16. Freeze Drying ProcessZydis and Lyoc technology- drug is physically entrapped inmatrix composed of saccharide e.g. mannitol and a polymerpiroxicam, loperamide, ondansetron, chlorpheniramine arevarious drugs taste-masked by Zydis technology. 5/17/2012 30
  31. 31. 17. Viscosity ModificationsIncreasing viscosity with gums or carbohydrates can lower thediffusion of drug.decrease contact between bitter drugs and the taste receptors.thickening agents such as PEG and NaCMC.Acetaminophen suspension with xanthan gum (0.1‐0.2%) andmicrocrystalline cellulose (0.6‐1%).Gelatine and flavours (chocolate flavour) mask the bitter taste oftannic acid by viscosity effects, form jelly on cooling. 8. Wax Embedding of DrugTastes masked by embedded granules of ephedrine HCl,Chlorpheniramine maleate, Diphenhydramine HCl were preparedin stearic acid & other waxes. 5/17/2012 31
  32. 32.  Evaluation of Taste Masking Effecttedious work as the taste sensation varies person to person.coated microsphere & Ion exchange resin- drug release rate canserve as an index of the degree of masking achieved. Sensory evaluationIt is possible to accurately and reproducibly measures tastethresholds.To quantitatively evaluate taste sensation, following methods used1. Panel testing (human subjects)2. Measurement of frog taste nerve responses.3. Multichannel taste sensor/ magic tongue4. Spectrophotometric evaluation/ D30‟s value 5/17/2012 32
  33. 33. 1] Panel Testing  In vivo Evaluation  The panel testing is a psychophysical rating of the gustatory stimuli.  5‐10 human volunteers with organoleptic sense.  reference solutions ranging in taste from tasteless to very bitter.  Normal dose was held in mouth for 60 seconds.  Bitterness recorded against pure drug (test solution) is tasted and rated on the same numerical scale to assess its bitterness.Numerical values are then assigned to these levels of bitterness(eg.,0‐5). 0 = pleasant, 1 = Tasteless, 2 = No bitter but after taste give bitterness, 3 = immediately gives bitterness, 4 = slightly bitter, 5 = extremely bitter. 5/17/2012 33
  34. 34.  Demands large panels and elaborate analysis, raises safety and scheduling issues and Time consuming and expensive.2] Measurement of Frog Taste Nerve ResponsesAdult bull frogs glossopharyngeal nerve is located and dissectedfrom the surrounding tissue and cut proximallyAn ac‐amplifier and an electronic integrator used to amplify andintegrate the nerve impulses.The peak height of the integrated response is then taken as themagnitude of response. 5/17/2012 34
  35. 35. 3] Multichannel Taste Sensor / Magic tongueIn vitro Evaluation“E-Tongue” automated taste sensing device- detect magnitude ofbitterness. Overcomes problems of panel testing.recognition, quantitative multicomponent analysis and artificialassessment of taste and flavour.It recognizes three levels of biological taste including1] Receptor level (Taste buds in humans, probe membranes in E-Tongue),2] circuit level (neural transmission in humans, transducer in E-Tongue), and3] perceptual level (cognition in the thalamus humans, computerand statistical analysis in the E-Tongue).Transducers composed lipid/polymer membranes to detect taste aslike to human gustatory sensation. 5/17/2012 35
  36. 36. Probes consist of a silicon transistor with proprietary organiccoatings, which govern the probe‟s sensitivity and selectivity, andmeasurement done potentiometrically.statistical software interprets the sensor data into taste patterns.Liquid samples directly analysed, solids require to dissolve.Reference electrode and sensors are dipped in a beakercontaining a test solution for 120 seconds (as shown in fig.).A potentiometric difference between each sensor and areference electrode measured and analyzed by software.e.g. Quantification of Suppression of bitterness of Quinine bysucrose. E-Tongue enables us to test taste accurately without the need for human volunteers at earlier stages. E-Tongue lose its sense of taste after long periods of testing 5/17/2012 36
  37. 37. Fig. : Evaluation of taste using e-tongue 5/17/2012 37
  38. 38. 4] Spectrophotometric Method A known quantity of the taste‐masked formulation is mixed with 10 ml of distilled water in 10 ml syringe by revolving the syringe, end to end, five times in 30 seconds. test medium then filtered through a membrane filter, followed by spectrophotometric determination of the concentration of the drug in the filtrate. If this concentration is below the threshold concentration, it may be concluded that the bitter taste would be masked in vivo. This technique has been applied to evalute the taste masked granules of sparfloxacin, with threshold concentration being 100μg/ml. 5/17/2012 38
  39. 39.  References  K.P. Sampath Kumar, THE PHARMA INNOVATION-Taste Masked Suspension,, Vol. 1 No. 2 (2012), Page no.- 1-6.  Nilesh Jain, Effect of superdisintegrants on formulation of taste masked fast disintegrating Ciprofloxacin tablets, International Current Pharmaceutical Journal 2012, 1(4): Page no.- 62-67.  Velmurugan S, Oral Disintegrating Tablets: An Overview, International Journal of Chemical and Pharmaceutical Sciences 2010, Dec., Vol.1 (2): Page no.- 1-10.  A. M. Suthar, Ion Exchange Resin As An Imposing Method For Taste Masking: a Review, An International Journal of Pharmaceutical Sciences, Vol-1, Issue-2, (2010), Page no.- 6-10.  Aditi Tripathi, Taste Masking: A Novel Approach for Bitter and Obnoxious Drugs, Journal of Pharmaceutical Science Bioscientific Research, Volume 1, Issue 3: Nov -Dec 2011 Page no.- 136-142. 5/17/2012 39
  40. 40.  Zelalem Ayenew, Trends in Pharmaceutical Taste Masking Technologies: APatent Review, Recent Patents on Drug Delivery & Formulation 2009, 3, Pageno.- 26-39. S. T. Birhade, Preparation and Evaluation of Cyclodextrin Based BinarySystems for Taste Masking, International Journal of Pharmaceutical Sciences andDrug Research 2010; 2(3): Page no.- 199-203. Patidar ashish, A Review On- Recent Advancement In The Development ofRapid Disintegrating Tablet, International Journal of Life science & PharmaResearch, Vol 1/Issue 1/Oct-Dec 2011, Page no.- 7-15. Rajesh Agrawal, Cyclodextrins – A Review on Pharmaceutical Application forDrug Delivery, International Journal of Pharmaceutical Frontier Research, Jan-Mar 2012; 2(1), Page no.- 95-112. Vijay D. Wagh, Taste Masking Methods and Techniques in OralPharmaceuticals: Current Perspectives, Journal of Pharmacy Research 2009, 2(6),Page no.- 1049-1054. 5/17/2012 40
  41. 41.  Gupta A. K., Practical Approaches for Taste Masking of Bitter Drug: AReview, International Journal of Drug Delivery Technology, 2010; 2(2), Page no.-56-61. S. B. Ahire, A Review: Taste Masking Techniques in Pharmaceuticals, AnInternational Journal of Pharmaceutical Sciences, IC Value – 4.01, Page no.-1645-1657. Vijay A. Agrawal, Taste Abatement Techniques to Inprove Palatability of OralPharmaceuticals: a Review, International Journal of Pharma Research andDevelopment, 2010/VOV-2/ISSUE-7/SEP/008, Page no.- 1-7. 5/17/2012 41
  42. 42. Thank you…5/17/2012 42