Taste masking methods in pharmaceutical formulations

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Taste masking methods in pharmaceutical formulations

  1. 1. A Seminar on Taste Masking Methods in Pharmaceutical FormulationsPresented by Sagar B. Thoke M. Pharm IInd Semester [Dept. of Pharmaceutics]Guided by Prof . Y. P. Sharma S.N.D. College of Pharmacy, Babhulgaon.
  2. 2. Introduction Introduction Factors Affecting Selection of Taste Masking Technology Factors Consideration During The Taste-Masking Formulation Process Ideal Characteristics of Taste Masking Process & Formulation Taste Masking Approaches Evaluation Techniques 2 7/16/2012
  3. 3. Introduction Need to Formulate Taste Masked Oral formulations. Children, older persons-  Trouble swallowing tablets or capsules  Prefer liquid or sublingual/ Chewable solid form dosage form Undesirable taste-  Important formulation problems in case of Oral formulation  Patient compliance 3 7/16/2012
  4. 4. Anatomy & Physiology of Tongue Vasculature  Lingual artery  Jugular vein Nerve supply  Facial nerve CN VII  Glossopharyngeal nerve CN IX Musculature Fig. Physiology of Taste Bud  Intrinsic  Extrinsic Tongue physiology  Taste buds (taste cells)  Sense different tastes 4 7/16/2012
  5. 5.  Four fundamental sensations of taste  Sweet and salty, mainly at the tip  Sour, at the sides  Bitter, at the back  fifth is Umami (2002) Taste Signaling Pathways Fig. Taste Points in Tongue 1. Drug (tastant) binds with G-PCR in the cells 2. triggering the release the release of G-Protein (Gustducin) 5 7/16/2012
  6. 6. Taste Blocking Mechanism 6 7/16/2012
  7. 7. Factors Affecting Selection of Taste Masking Technology Conventional taste masking techniques alone are often inadequate in masking the taste of highly bitter drugs such as quinine, celecoxib. Coating imperfections, reduce the efficiency of the technique. Microencapsulation of potent bitter azithromycin is insufficient to provide taste masking of liquid oral suspensions. 7 7/16/2012
  8. 8. Factors Consideration During The Taste-Masking Formulation Process1. Extent of the bitter taste of the API & Required dose load.2. Drug particulate shape and size distribution.3. Drug solubility and ionic characteristics.4. Required disintegration and dissolution rate of the finished product.5. Desired bioavailability & release profile.6. Required dosage form. 8 7/16/2012
  9. 9. Ideal Characteristics of Taste Masking Process & Formulation It should 1. Involve least number of equipments and processing steps. 2. Effectively mask taste with as few excipients which are economically and easily available. 3. No adverse effect on drug bioavailability. 4. Least manufacturing cost. 5. Can be carried out at room temperature. 6. Require excipients that have high margin of safety. 7. Rapid and easy to prepare. 9 7/16/2012
  10. 10. Taste Masking Approaches Two approaches are commonly utilized 1. By reducing the solubility of drug in the pH of saliva (5.6 - 6.8). 2. By altering the affinity and nature of drug which will . interact with the taste receptor. 10 7/16/2012
  11. 11. Taste Masking Technologies  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%.Fig. Geographical distribution of taste masking patents &patent application filed in the period of year 1997 to 2007. 11 7/16/2012
  12. 12. Fig. Taste masking technology filed in the period of year 1997 to 2007. 12 7/16/2012
  13. 13. Fig. Taste Masking Technologies uses in liquid and solid dosage forms 13 7/16/2012
  14. 14. 1. Taste Masking with Sweeteners and Flavors Flavors  Natural Flavors- Juices – Raspberry, Extracts – Liquorices, Tinctures – Ginger, Spirits - Lemon & Orange, Syrups – Blackcurrant, Aromatic waters - Anise & Cinnamon, Aromatic Oils – Peppermint & Lemon.  Synthetic Flavors- Alcoholic solutions, aqueous solutions, Powders. Sweeteners  Complement flavors associated with sweetness  Soothing effect on the membranes of the throat 14 7/16/2012
  15. 15. Sweeteners used for taste maskingNatural Artificial Nutritive Non- Polyols Novel NutritiveSucrose, Saccharin, Sucrose, Aspartam, Mannitol, Trehalose,Glucose, Saccharin Fructose, Sucralose, Sorbitol, Tagatose.Fructose, Sodium, Glucose Neotame, Xylitol,Sorbitol, Aspartame Saccharine Erythritol,Mannitol, MaltitolHoney,Glycerol,Liquorice 14 15 7/16/2012
  16. 16. 2. Polymer Coating of Drug Coating acts as a physical barrier to the drug particles, by minimizing interaction between the drug and taste buds.  Powders (50 mm) is fluidized by heated, high-velocity air, and the drug particles are coated with a coating solution introduced from the top as a spray through a nozzle.  Nontoxic polymer that is insoluble at pH 7.4 and soluble at acidic pH are used.  chewable tablet of crystalline ibuprofen and methacrylic acid Fig. Coating process copolymer coating. 16 7/16/2012
  17. 17. 3. Formation of Inclusion Complexes Complexation of guest molecule with host form a stable complex. 1. Decreasing its oral solubility or 2. Decreasing the amount of drug particles exposed to taste buds.  most suitable only for low dose drugs.  β-CD cyclic oligosaccharide obtained from starch. Fig. Scanning electron micrograph of uncoated (bitter) and coated (taste masked) paracetamol particles. 17 7/16/2012
  18. 18. 4. Ion Exchange Resin Complexes (IER) IERs- high mole. weight polymers with cationic and anionic functional groups. Most drugs possess ionic sites in their molecule. Drug-resin complex does not dissociate at salivary pH conditions. Classification Strong cation exchanger- sulphuric acid sites Weak cation exchanger- carboxylic acid moieties Strong anion exchanger- quaternary amine ionic sites Weak anion exchanger- predominantly tertiary amine substituentse.g. Indion 204, 234, 244, 254; Tulsion T-335, T- 339, T-334; Amberlite IRC 50, IRP 69, IRP 88, IR 120; Dowex 50. Not used- Amberlite IR400; Amberlite IR4B; Dowex 1; Indion 454; Duolite AP143. 18 7/16/2012
  19. 19. 5. Solid Dispersion One or more active ingredients Dispersed in an inert carrier or matrix at solid state. Carriers used- povidone, PEG, HPMC, urea, mannitol and ethylcellulose. Methods of Preparation  Melting method  Solvent method  Melting solvent method Dimenhydrinate with polyvinyl acetate phthalate solid dispersion . 19 7/16/2012
  20. 20. 6. Microencapsulation Thin coating to small particles of solids, droplets of liquids and dispersions. Reduce its solubility in saliva & Act as physical barrier between drug and taste buds Coating agents e.g. • Gelatin, povidone, hydroxyethyl cellulose, ethyl cellulose, bees wax, carnuba wax acrylics and shellac. • water insoluble polymers- cellulose ethers, cellulose ester, polyvinyl acetate and • water soluble polymers- cellulose acetate butyrate, PVP, hydroxyethyl cellulose. Clarithromycin with combination of gelatine and acrylic resins (Eudragit L-100, Eudragit S-100 & E-100). 20 7/16/2012
  21. 21. 7. Multiple Emulsions API entrapped in internal phase of w/o/w or o/w/o emulsion. w/o/w or o/w/o emulsion of chloroquine phosphate. 8. Development of Liposome Liposomes- simple microscopic vesicles in which aqueous volume (drug or biological agent) is entirely closed by a membrane composed of lipid molecules.  lipid bilayers mainly composed of natural or synthetic phospholipids. e.g. phosphatidic acid, phosphatidylinositol, soy lecithin.Chloroquine phosphate in HEPES (N-2-hydroxyetylpiperzine-N’-2- ethane sulfonic acid) buffer was masked at pH 7.2. byincorporating into egg phosphatidyl choline. 21 7/16/2012
  22. 22. 9. Prodrug Approach Chemically modified inert drug precursor upon biotrans- formation liberates the pharmacologically active parent compound. changing the molecular configuration of the parent molecule taste receptor‐substrate adsorption constant may be modified.Increase or decrease the aqueous solubility, mask bitterness,increase lipophilicity, improve absorption, decrease local sideeffects, and alter membrane permeability of the parent molecule.Examples of Prodrugs with improved taste Parent Drug Prodrug Erythromycin Erythromycin Propionate Clindamycin Clindamycin palmitate ester 22 Chloramphenicol Chloramphenicol palmitate ester 7/16/2012
  23. 23. 10. Taste Masking by Adsorption Adsorbate of Drug are less saliva soluble versions of drugs. Solution of the drug mix with an insoluble powder that will absorb the drug, removing the solvent, dry it.e.g. veegum, bentonite, silica gel and silicates.Loperamide and phenyl propanolamine Suspension-adsorbed on magnesium aluminium silicates (Veegum F). 11. Taste Masking with Lipophilic Vehicles like Lipids and Lecithins Oils, surfactants, polyalcohols, and lipids effectively increase the viscosity in the mouth and coat the taste buds.Talampicillin HCl- Magnesium aluminum silicate with soybeanlecithin. 23 7/16/2012
  24. 24. 12. Taste Suppressants and Potentiators Suppressants (bitter taste blockers) compete with bitter substances to bind with the G-protein coupled (GPCR) receptor sites. Not affecting taste due to the sugars, amino acids, salts or acids. Bitter substances (hydrophobic) contributes greatly to their binding and inter-action with the receptor sites.• Lipoproteins (phosphatidic acid and β-lactoglobulin)• adenosine monophosphate• Phospholipid (BMI-60)• hydroxyl flavanones & γ-aminobutanoic acid Mixture of cooling (e.g. eucalyptol) and warming agents (e.g. methyl salicylate) was used for taste masking of thymol. 24 7/16/2012
  25. 25.  Potentiators increase the perception of the taste of sweeteners.• thaumatine,• neohesperidine dihydrochalcone (NHDC) and• glycyrrhizin Increase the perception of sodium or calcium saccharinates, saccharin, aspartyl-phenyl-alanine, cyclamates. Desensitizing agents desensitize the taste buds by interfering with taste transduction. • phenols • sodium phenolates 25 7/16/2012
  26. 26. 13. Taste masking by gelation Water insoluble gelation on the surface of tablet containing bitter drug . Sodium alginate- form water insoluble gelation in presence of bivalentmetal ions. In presence of saliva, sodium alginate react with bivalent calcium and form water insoluble gel and thus taste masking achievedAmiprolose hydrochloride tablet undercoat of sodium alginateand overcoat of calcium gluconate. 26 7/16/2012
  27. 27. 14. Formation of salt and derivative Salt formation decreasing the solubility of drug (less soluble in saliva).• N, N- dibenzyl ethylenediamine diacetate salts or• N, N bis (deyhdroabiety) ethylene diamine salts is tasteless. Ibuprofen water-soluble salts using alkaline metal bicarbonate (sodium bicarbonate). Aspirin tablets with magnesium salt of aspirin. Sodium salts- sodium chloride, sodium acetate, sodium gluconate 27 7/16/2012
  28. 28. 15. Use of Amino Acids and Protein Hydrolysates Amino acids or their salts with bitter drugs.• sarcosine,• alanine,• taurine,• glutamic acid, and• glycine.Ampicillin taste improved by its granules with glycine andadditional quantity of glycine, sweeteners, flavors at finalcompression step. 28 7/16/2012
  29. 29. 16. Miscellaneous a) By effervescent agentsIt comprises chewing gum base an orally administrable medicament Taste masking generator of carbon dioxide optionally a taste bud desensitizing composition e.g. oral anaesthetics (benzocaine and spilanthol) and other non active material, (sweeteners, flavours, and fillers).Fentanyl and prochlorperazine effervescent tablets forbuccal, sublingual, and gingival absorption. 29 7/16/2012
  30. 30. b) Rheological modification Rheological modifier (gums or carbohydrates)- lower the diffusion of bitter substances from the saliva. For administration of liquid preparation.High viscosity induced by thickening agents• PEG and• sodium CMCAcetaminophen suspension using xanthan gum (0.1‐0.2%) andmicrocrystalline cellulose (0.6‐1%).Mirtazapine (antidepressant) aqueous suspension using methonine(stabilizer) and maltitol (thickening agent).  Terbutaline cough syrups given in doses of 4mg/5ml. 30 7/16/2012
  31. 31. c) Continuous multipurpose melt (CMT) technology Continuous granulation and coating of API. d) Wet Spherical Agglomeration (WSA) Microencapsulation process combined with wet spherical agglomeration (WSA). E.g. Enoxacin taste masking. 31 7/16/2012
  32. 32. e) Freeze Drying Process Used to develop FDT.  Zydis and Lyoc technology- drug is physically entrapped in matrix composed of saccharide e.g. mannitol and a polymer.  piroxicam, loperamide, ondansetron, chlorpheniramine are various drugs taste-masked by Zydis technology. 32 7/16/2012
  33. 33. Evaluation Techniques Taste masking efficiency as  Quality control parameter and  Determining the rate of release of drug from taste-masked complex. Asses by  in vivo and  in vitro. To quantitatively evaluate taste sensation, following methods have been reported a. Human Panel testing (human subjects) b. Multichannel taste sensor/ magic tongue c. Spectrophotometric evaluation/ D30’s value 33 7/16/2012
  34. 34. In vivo Evaluationa. Human Panel testing (human subjects) 5‐10 healthy volunteers with organoleptic sense. Taste evaluation using reference solutions ranging from tasteless to very bitter. Place the dosage form in mouth for 10 seconds.  Demands large panels and elaborate analysis.  raises safety and scheduling issues.  time consuming and expensive. Two sensory analysis methods used-  Flavor Profile and  Profile Attribute Analysis 34 7/16/2012
  35. 35. Bitterness recorded against pure drug using a numerical scale.seven point scale1 = no bitterness,2 = very slight bitterness,3 = slight bitterness,4 = slight to moderate bitterness,5 = moderate bitterness,6 = moderate to strong bitterness, and7 = strong bitterness.untrained taster would perceive an objectionable and/ornoticeable bitterness if the bitterness score is greater than orequal to 3. 37 7/16/2012
  36. 36. In vitro Evaluationb. Multichannel Taste Sensor / Magic tongueautomated taste sensing device to detect the magnitude ofbitterness.“E-Tongue” electronic sensor array technology recognizes threelevels of biological taste including 1. receptor level (Taste buds in humans, probe membranes in E-Tongue), 2. circuit level (neural transmission in humans, transducer in E- . Tongue), and 3. Perceptual level (cognition in the thalamus humans, computer . and statistical analysis in the E Tongue). 38 7/16/2012
  37. 37.  Seven (7) sensors designated by Alpha MOS ZZ, AB, BA, BB, CA, DA, and JE. chemically modified sensors- field effect transistors (Chem FET), similar to an ion selective FET but are coated with a proprietary coating/membrane. Ag/AgCl reference electrode probes consist of a silicon transistor with proprietary organic coatings. measurement done potentiometrically. taste profile and statistical software interprets the sensor data into taste patterns. 39 7/16/2012
  38. 38.  Reference electrode and sensors are dipped in a beaker containing a test solution for 120 seconds. 40 7/16/2012
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  40. 40. Click 2 times on the below image 43 7/16/2012
  41. 41. c. Spectrophotometric Method known quantity of formulation mixed with 10 ml of distilled water in 10 ml syringe by revolving the syringe, end to end; five times in 30 seconds. filtered through a membrane filter & 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. Sparfloxacin granules, with threshold concentration being 100μg/ml. Generally the taste evaluation involves  objective or analytical method and  subjective or hedonic method 44 7/16/2012
  42. 42. ConclusionTaste masking of bitter drugs has been a challenge to the scientist.There are numbers of technologies available, which effectivelymask the objectionable taste of drugs. Selection of technologydepends upon the bitterness of drugs and their compatibility withtaste masking agents that does not affect the bioavailability ofdrug. With application of these techniques and proper evaluationof taste masking effect one can improve product preference to alarge extent. Moreover, the development of taste maskingmethodology requires great technical skill, and the need formassive experimentation. 45 7/16/2012
  43. 43. References1) Gupta A. K., Practical Approaches for Taste Masking of Bitter Drug: A Review, International Journal of Drug Delivery Technology (April-June 2010), Vol. 2, Issue 2, Page no.- 56-61.2) S. B. Ahire, A Review: Taste Masking Techniques in Pharmaceuticals, An InternationalJournal of Pharmaceutical Sciences (2011), Page no.- 1645-1657.3) Aditi Tripathi, Taste Masking: A Novel Approach for Bitter and Obnoxious Drugs,Journal of Pharmaceutical Science and Bioscientific research (Nov-Dec 2011), Vol. 1,Issue 3, Page no.- 136-142.4) Vijay D. Wagh, Taste Masking Methods and Techniques in Oral Pharmaceuticals:Current Perspectives, Journal of Pharmacy Research (2009), Vol. 2, Issue 6, Page no.-1049-1054.5) Vijay A. Agrawal, Taste Abatement Techniques to Inprove Palatability of OralPharmaceuticals: A Review, International Journal of Pharma Research and Development(Sep. 2010), Vol. 2, Issue 7, Page no.- 1-10. 46 7/16/2012
  44. 44. 6) Vinod M. Sonawane, An Update of Taste Masking Methods and EvaluationTechniques, Scholars Research Library, Der Pharmacia Lettre (2010), Vol. 2, Issue 6,Page no.- 1-15.7) Sidharth Puri, Taste Masking: A Novel Approch For Bitter And Obnoxious Drugs,International Journal of Biopharmaceutical & Toxicological Research (May 2011), Vol.1, Issue 1, Page no.- 47-56.8) J.K. Lorenz et al., Evaluation of a Taste Sensor Instrument (electronic tongue) for UseIn Formulation Development, International Journal of Pharmaceutics (2009), Page no.-65–72.9) K Gowthamarajan, Taste-Masking Technologies for Bitter Drugs, General ArticleResonance (December 2004), Page no.- 25-32.10) Arvind K. Bansal, Trends in Pharmaceutical Taste Masking Technologies: A PatentReview, Recent Patents on Drug Delivery & Formulation (2009), 3, Page no.- 26-39. 47 7/16/2012
  45. 45. 11) A. M. Suthar, Ion Exchange Resin As An Imposing Method For Taste Masking: aReview, An International Journal of Pharmaceutical Sciences (2010), Vol-1, Issue-2, Pageno.- 6-11.12) Sanjay Daharwal, Taste Masking Method for Bitter Drug and Tasteless DispersibleTablet: An Overview, Page no.- 1-9.13) Rajesh Agrawal, Cyclodextrins – A Review on Pharmaceutical Application for DrugDelivery, International Journal of Pharmaceutical Frontier Research (Jan-Mar 2012), Vol.2, Issue 1, Page no.- 95-112.14) K.P. Sampath Kumar, Taste Masked Suspension, www.thepharmajournal.com(2012), Vol. 1 No. 2, Page no.- 1-6.15) S. T. Birhade, Preparation and Evaluation of Cyclodextrin Based Binary Systems forTaste Masking, International Journal of Pharmaceutical Sciences and Drug Research(2010), Vol. 2, Issue 3, Page no.- 199-203.16) Inderbir SINGH, Scientific Review Ion Exchange Resins: Drug Delivery andTherapeutic Applications, FABAD J. Pharm. Sci. (2007), 32, Page no.- 91-100. 48 7/16/2012
  46. 46. Thank You…! 49
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