Successfully reported this slideshow.

Taste masking approaches

5,085 views

Published on

Includes Physiology of taste sensation and various techniques for taste masking & criterias for selection of proper taste masking technique

Published in: Education, Business, Technology

Taste masking approaches

  1. 1. Taste Pathway
  2. 2. Ventral posterior medial nucleus of thalamus or parietal cerebral cortex (nuclei of tractus solitarius)
  3. 3. Epithelial cells in taste buds Supporting cells Gustatory receptor cells Basal cells
  4. 4. Papillae for taste Vallate Papillae Fungiform Papillae Foliate Papillae
  5. 5. CLINICAL CONSIDERATIONS Ageusia: Absence of sense of taste Dysgeusia: Disturbed sense of taste Hypogeusia: Diminshed sense of taste Hypergeusia: increased sense of taste
  6. 6. Trends in Pharmaceutical Taste Masking Technologies: A Patent Review Z. Ayenew, V. Puri, L. Kumar and A. K. Bansal, Recent Patents on Drug Delivery & Formulation 2009, 3, 26-39. Department of Quality Assurance ISF COLLEGE OF PHARMACY MOGA – 142001 Presented by:- Saurav Bhandari
  7. 7. INTRODUCTION • The flavor of a substance is attributed to its taste, sight, odor and qualities such as mouth feel. • Taste refers to a perception arising from the stimulation of taste buds present on the surface of the tongue. • Humans can distinguish among five components of taste: 1. 2. 3. 4. 5. Sourness Saltiness Sweetness Bitterness Umami (savory)
  8. 8. INTRODUCTION • The sweet, salty and the sour-taste receptors are concentrated on the tip and both edges of the tongue. • Bitter taste is perceived by the receptors at the back of the tongue. • Umami taste receptors are located all over the tongue. • This article focuses on the current trends in the taste masking technologies summarized from the state of art patents filed in the 10 year span of 1997 to 2007 in this field. • It discusses the reported taste masking technologies and the factors governing the selection of taste masking strategies for a particular drug.
  9. 9. CURRENT TRENDS IN TASTE MASKING TECHNOLOGIES • The worldwide database of European patent office (http:// ep.espacenet.com) was used to search the taste masking patents and the patent applications published in the period of year 1997 to 2007.
  10. 10. CURRENT TRENDS IN TASTE MASKING TECHNOLOGIES • Taste masking technologies are increasingly focussed on aggressively bitter tasting drugs like 1. 2. 3. Macrolide anti-biotics Non-steroidal anti-inflammatory drugs Peni-cillins • Taste masking of water soluble bitter drugs, especially those with a high dose, is difficult to achieve by using sweeteners alone. As a consequence, more efficient techniques such as coating, microencapsulation and granulation have been used in combination with the sweeteners.
  11. 11. CURRENT TRENDS IN TASTE MASKING TECHNOLOGIES • Coating, which accounts for 27% of patents and patent applications, was the most commonly used technique. • An almost equivalent percentage of patents were filed on the flavors and sweeteners for taste masking. • Microencapsulation, granulation technologies, suppressants potentiators also hold a prominent share of patents in this field. • Less commonly used taste masking technologies were viscosity modifiers, solid dispersions, complexing agents, ion exchange resins, pH modifiers these hold 5% share of the total taste masking patents. and
  12. 12. TREND ANALYSIS PERIODS SWEETENERS COATING 1997-2000 Prominent 2001-2004 41.6% Increase 133% Increase 2005-2007 No Increase 78.6% Increase
  13. 13. TASTE MASKING TECHNOLOGIES
  14. 14. COATING • Coating is one of the most efficient and commonly used taste masking technologies. • It is classified based on the type of coating material, coating solvent system, and the number of coating layers. • Hydrophobic polymers, lipids, sweeteners and hydrophilic polymers can be used as coating materials, either alone or in combination, as a single or multilayer coat. • Hydrophobic polymers have been popularly used for coating bitter medicaments to achieve taste masking. However, hydrophilic polymers may also provide taste masking. For example, rotogranules containing ibuprofen, polyvinylpyrrolidone, sodium starch glycolate and sodium lauryl sulfate were coated with hydrophilic polymers such as hydroxyethyl cellulose or a mixture of hydroxyethyl cellulose and hydroxypropyl methylcellulose to achieve taste masking.
  15. 15. COATING • Combinations of pH independent water insoluble polymers such as cellulose ethers, cellulose ester, polyvinyl acetate and water soluble polymers such as cellulose acetate butyrate, polyvinylpyrollidone, hydroxyethyl cellulose have been used to attain a balance between the taste masking and in vitro release. • This approach may not be effective for the oral liquid dosage forms such as suspensions due to a gradual loss of taste masking efficiency upon storage in the liquid form. In such cases, pH independent water insoluble polymers can be combined with the enteric or reverse enteric polymers to increase the taste masking efficiency. • The pH of formulation maintained between 3.5 and 5 by adding a buffering agent to prevent the dissolution of polymers. This approach can provide an efficient taste masked suspensions over a long storage time.
  16. 16. GRANULATION • Mixture of bitter medicaments and sweeteners, hydrophobic polymers, lipids or waxes can be processed by dry, wet and melt granulation techniques to prepare taste masked oral solid or liquid dosage forms. • Granulation is a less expensive, rapid operation and an easily scalable taste masking technology. • pH dependent and independent water insoluble polymers, especially the swelling polymers such as MCC and polycarbophil have been employed. • During granulation, particle coating may remain incomplete. However, a swelling matrix phenomenon can reduce the overall diffusion of the bitter active. Thus, swellable polymers can give a better taste masking in granulation compared to non swellable polymers.
  17. 17. SWEETENERS • Sweeteners are commonly used in combination with other taste masking technologies. They can be mixed with bitter taste medicaments to improve the taste of the core material which is prepared for further coating or may be added to the coating liquid. • Artificial sweeteners such as sucralose, aspartame and saccharin have been used in combination with sugar alcohols such as lactitol, maltitol and sorbitol to decrease the after-taste perception of artificial sweeteners. Sucralose can be used with physiologically acceptable acids (e.g. citric acid) to increase the taste masking efficiency of the sweetener.
  18. 18. Sweetener(s) Sucralose and acids(e.g. citric acid) Sucralose Drug(s) Acetaminophen, guaifenesin and dextromethorphan hydrobromide Amino acids(e.g. Lalanine and L-aspartic acid and other Amino acids except arginine), protein hydrolysates and proteins Comments Citric acid Low pH(2 to 5) and use of as a sweetener achieves an unexpected synergy of bitter taste masking effectiveness Improved taste without an unpleasant, bitter/metallic taste or after-taste of ingestible products
  19. 19. MICROENCAPSULATION • Coating by enteric polymers in combination with water insoluble and gastrosoluble polymers have been used for masking the unpleasant taste of medicaments. Combination of water soluble polymer like gelatin, and water insoluble coating polymer like ethyl-cellulose was used to prepare taste masked microcapsules by the phase separation method. • pH independent water insoluble polymers have been used with enteric polymers, to achieve taste masking by microencapsulation. Buffering agents are also included in suspending medium to increase taste masking efficiency of microcapsules in oral suspensions.
  20. 20. TASTE SUPPRESSANTS AND POTENTIATORS • Taste suppressants compete with bitter substances to bind with the Gprotein coupled (GPCR) receptor sites. • Lipoproteins are universal bitter taste blockers. Study on animal model showed that lipoproteins composed of phosphatidic acid and β lactoglobulin inhibit the taste nerve responses to the bitter substances without affecting those due to the sugars, amino acids, salts or acids. • Mixture of cooling (e.g. eucalyptol) and warming agents (e.g. methyl salicylate) was used for taste masking of thymol. • Potentiators increase the perception of the taste of sweeteners and mask the unpleasant after taste. Potentiators such as thaumatine, neohesperidine dihydrochalcone(NHDC) and glycyrrhizin can increase the perception of sodium or calcium saccharinates, saccharin, acesulfame
  21. 21. TASTE SUPPRESSANTS AND POTENTIATORS • The recent trend of use of bitter taste blockers such as hydroxyflavanones, adenosine monophosphate and gamma-aminobutanoic acid were found to be effective to achieve the taste masking of bitter drugs.
  22. 22. SOLID DISPERSIONS • Specific interactions between poorly soluble drugs and hydrophilic polymers can increase the solubility of the drug Solution of quinolone + the natural hydrophobic polymer shellac solvent evaporation Taste masked solid dispersion This approach usually requires a higher concentration of excipients compared to other taste masking techniques. Natural polymers such as shellac and zein Enteric poly-mers like derivatives of acrylic acid polymers and phthalate are good choices to develop the taste masked solid dispersions.
  23. 23. ION EXCHANGE RESINS • Ion exchange resins are high molecular weight polymers with cationic and anionic functional groups. Resins form insoluble resinates + oppositely charged drugs Form weak ionic bonding & maintain low concentration of the free drug in a suspension After ingestion, the resinate exchange the drug with the counter ion in gastrointestinal tract The drug is eluted & get absorbed
  24. 24. VISCOSITY ENHANCERS Viscosity Enhancers Retard the migration of dissolved medicament from the surface of the solid particle to the suspending medium Decrease the contact between the bitter medicament and the taste receptors
  25. 25. VISCOSITY ENHANCERS • Hypromellose was used as a viscosity modifier in taste masked azelastine suspension consisting of sucralose as the sweetening agent • Viscosity enhancers included in suspending vehicle to improve the taste masking efficiency some examples include1. Xanthan gum 2. Microcrystalline cellulose 3. Sodium carboxymethyl cellulose
  26. 26. COMPLEX FORMATION Complex Formation Cyclodextrins wraps the bad tasting molecule to inhibit its interaction with the taste buds Interacts with the gatekeeper proteins of the taste buds Sweeteners such as acesulfame can form complex with medicaments to achieve taste masking.
  27. 27. pH MODIFIERS pH Modifying agents Generate a specific pH microenvironment in aqueous media Cause in situ precipitation of the bitter drug substance in saliva Reduce the overall taste sensation for liquid dosage forms like suspension
  28. 28. ADSORBATES Drug + Adsorbate The drug may be adsorbed or/and entrapped in the matrix of the porous component (Adsorbate) Result in a delayed release of the bitter active during the transit through the oral cavity
  29. 29. FACTORS AFFECTING SELECTION OF TASTE MASKING TECHNOLOGY
  30. 30. 1. 2. 3. 4. 5. 6. Extent of Bitter Taste Dose of Active Pharmaceuticals Drug Particle Shape and Size Distribution Dosage Forms Drug Solubility Ionic Characteristics of the Drug
  31. 31. EXTENT OF BITTER TASTE With aggressively bad tasting medicaments even a little exposure is sufficient to perceive the bad taste. • Coating is more efficient technology for aggressively bitter drugs even though coating imperfections, if present, reduce the efficiency of the technique • Microencapsulation of potent bitter active agents such as azithromycin is insufficient to provide taste masking of liquid oral suspensions. • Viscosity enhancers can complement the taste masking efficiency. Oral suspension containing viscosity enhancers can mask the objectionable taste.
  32. 32. DOSE OF ACTIVE PHARMACEUTICALS • Dose of a drug may dictate whether a particular formulation strategy would be suitable to achieve taste masking • Low dose palatable pediatric aspirin oral formulation was developed by adding sweeteners, but the same approach failed to address the problem of drugs like acetaminophen because of its high dose • Coating will be the preferred techinique if dose of drug is high
  33. 33. DRUG PARTICLE SHAPE AND SIZE DISTRIBUTION • Core materials with irregular shapes and small particle size lead to poor taste masking efficiency and varying dissolution of coated particles Granules of irregular particles are prepared Coating using internal spacing layer Coating layer for taste masking to avoid any misperfection in coating
  34. 34. DOSAGE FORMS • Chewable tablets and liquid oral formulations are preferable in case of large dose drugs for an ease of intake. • Taste masking technologies such as sweeteners, particulate coating, microencapsulation and granulation can be employed for chewable tablets and supported with techno-logies such as viscosity enhancers and pH modifiers to achieve taste masking in liquid oral formulations • Microencapsulation of the unpleasant tasting active agent with ethyl cellulose or a mixture of ethyl cellulose and hydroxypropyl cellulose or other cellulose derivatives has been used to provide chewable tastemasked dosage forms. However, this approach is having disadvantage that it also affect release of drug from the formulation. So this is not good for drugs which are to be used for immediate release.
  35. 35. DRUG SOLUBILITY • Physicochemical properties of the drug play an important role in the selection of taste masking technology • Ondansetron has a relatively lower water solubility at higher pH, based on which a rapidly disintegrating taste masked composition of ondansetron was formulated by adding an alkalizing agent (sodium bicarbonate) to reduce the water solubility and also the taste perception Water Insoluble drug Water soluble drug Coat with a Lipid Formulated in aqueous media, so Coating with a Lipid is difficult Coat with polymeric binder
  36. 36. IONIC CHARACTERISTICS OF THE DRUG • Ionic characteristics of drugs govern the selection of ion exchange resin polymers • Anionic polymers (e.g. Alginic acid) are good candidates for cationic drugs like donepezil hydrochloride, and the cationic polymers are choice of excipients for anionic drugs like sildenafil
  37. 37. CURRENT & FUTURE DEVELOPMENTS • Use of sweeteners is an age old and most popular tool for disguising bitterness • The combination of sweeteners with other taste masking technologies including microencapsulation, particulate coating, bitterness blockers, ion exchange resins and potentiators is found to be a more efficient strategy. • Bitter taste blockers which specifically block the bitter taste but not the pleasant taste of any additive are being explored as universal taste masking alternatives. Presently, they are limited in number, and most of them not being GRAS (Generally Regarded As Safe) listed.
  38. 38. REFERENCES • Lindemann B. Umami taste receptor identified. Nature Neuro-science 2000. http://www.nature.com/neuro/press_release/nn0200. html(accessed on May 01, 2008). • Yonan J. Umami: Two cookbook authors hope to demystify the littleknown fifth taste. The Boston Globe 2006. http://www. boston.com/ae/food/articles/2006/03/15/umami/(accessed on May 01, 2008). • Roche, E.J., Papile, S.M., Freeman, E.M.: US5260072(1993). • Kulkarni, G.M., Menjoge, A.R.: CN1878539(2006). • Roche, E.J., Reo, J.P.: KR0166064B (1999). • Dumont, H., Thibert, R.: US20060228410 (2006). • Kokubo, H., Nishiyama, Y.: KR20010051807 (2001). • Yeong, J.S., Gil, K.M., Su, P.Y., Il, S.S., Sin, S.J.: KR0058861 (2003).
  39. 39. REFERENCES • • • • • • • • • Douglas, S.J., Evans, J.: CA2146999 (1994). Krise, H.E., Rajendra, K.K., John, H.: US20046740341 (2004). Naoto, O., Yasunobu, O.: JP327943 (2006). Nandi, I., Guo, M., Gassert, C.M.: US20050084540 (2005). Lai, J.W., Venkatesh, G.M., Qian, K.K.: US20060105039 (2006). Julian, T.N., Radebaugh, G.W.: KR970007899B (1997). Gandhi, R., Issa, C., Malik, R.: US20060159758 (2006). Paruthi, M.K., Bhonsle, S., Krishnan, A.: WO2004066984 (2004). Venkatesh, G.M.: US20060078614 (2006).

×