INTRODUCTION:

Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that are encountered with certain drugs. Oral administration of bitter drugs with an acceptable degree of palatability is a key issue for health care providers, especially for pediatric patients. Taste masking of bitter drugs has been challenge to scientists. Several oral pharmaceuticals and bulking agents have unpleasant bitter taste. In order to ensure patient compliance; bitterness masking becomes essential. Several oral pharmaceuticals, numerous food and beverage products and bulking agents have unpleasant, bitter-tasting components^1.Several approaches namely sensory, barrier, chemical and complexation have been tried to mask the unpleasant taste of formulation. Palatability is recognized as being a critical factor in patient compliance, particularly for children in whom the acceptability of medicament and hence its ease of administration can be greatly affected by taste. So, any pharmaceutical formulation with a pleasing taste would definitely be preferred over a competitor’s product and would translate into better compliance and therapeutic value for the patient leading to more business and profits for the company.

The problem of bitter and obnoxious taste of drug in pediatric and geriatric formulations is a challenge to the formulator in the present scenario. In order to ensure patient compliance bitterness masking becomes essential. The desire of improved palatability in these products has promoted the development of numerous formulations with improved performance and acceptability². Molecule interacts with taste receptor on the tongue to give bitter, sweet or other taste sensation, when they dissolve in saliva ³. This sensation is the result of signal transduction from the receptor organs for taste, commonly known as taste buds. These taste buds contain very sensitive nerve endings, which produce and transmit electrical impulses via the seventh, ninth and tenth cranial nerves to those areas of the brain, which are devoted to the perception of taste ^{4, 5}.

The methods most commonly involved for achieving taste masking include various chemical and physical methods that prevent the drug substance from interaction with taste buds. The simplest method involves use of flavor enhancers. Where these methods fail more complex methodologies are adopted. Many techniques have been developed which have not only improved the taste of product, but also the stability of the formulation and performance of the product. Various techniques have been identified for taste masking which include polymer coating, inclusion complex formation with cyclodextrin, use of ion exchange resins, solubility limiting methods, liposome, multiple emulsions, use of anesthetic agents, etc. The present review attempts to give a brief account of different technologies of taste masking with respect to dosage form along with novel methods of evaluation of taste masking effect. Two approaches are commonly utilized to overcome bad taste of the drug ^{6, 7}. The first includes reduction of drug solubility in saliva, where a balance between reduced solubility and bioavailability must be achieved. Second approach being commonly used to mask the bitter taste of a drug by ion exchange resins.

An ideal taste masking process, formulation and characterization should have the following 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) Require excipients that are economical and easily available

5) Least manufacturing cost

6) Can be carried out at room temperature

7) Require excipients that have high margin of safety

8) Rapid and easy to prepare

[I] Methods Employed for Taste Masking of Pharmaceuticals: The methods commonly employed for achieving effective taste masking include various physical and chemical methods that prevent the drug substance from interaction with the taste buds. Various methods are available to mask undesirable taste of the drugs. Some of these are as given below.

1) Use of Flavor Enhancers:

Flavoring and perfuming agents can be procured from either natural or synthetic sources. Natural products include fruit juices, aromatic oils such as peppermint and lemon oils, herbs, spices and distilled fractions of these (Table 1). They are available as concentrated extracts, alcoholic or aqueous solutions, syrups or spirit. Use of flavor enhancers are limited only to unpleasant tasting substances and is not applicable to oral administration of extremely bitter tasting drugs like various antibiotics. It is important to understand that only soluble portion of the drug can generate the sensation of taste. Addition of flavors and sweeteners is the most and simplest approach for taste masking especially in the case of pediatric formulation. However this approach has not been much successful for highly bitter and highly water soluble drugs. This approach also being used to improve the aesthetic appeal of the product especially to make it more attractive for pediatric patient as well as used for the liquid formulation and the chewable tablets ^{8, 9}

Table 1: Flavoring agents for taste masking

Basic Taste Masking agents
Sweet	Vanilla, Bubble gum, Grapefruit.
Acid	Lemon, Lime, Orange, Cherry, Grapefruit.
Metallic	Grape, Marsh, Mellow, Gurana, Berries, Mints.
Bitter	Liquorices, Coffee, Chocolate, Mint, Grapefruit, Cherry, Peach, Raspberry, Orange, Lemon, Lime.

2) Coating of drug particles with inert agents:

Coating is an extremely useful technique in masking of bitter drug and has many applications in the pharmaceutical field (Table-2). By coordinating the right type of coating material it is possible to completely mask the taste of a bitter drug, while at the same time, not adversely affecting the intended drug release profile ¹⁰. Any nontoxic polymer that is insoluble at pH 7.4 and soluble at acidic pH would be an acceptable alternative for taste masking. Taste masking of ibuprofen has been successfully achieved by using the air suspension coating technique to form microcapsules, which comprises a pharmaceutical core of a crystalline ibuprofen and methacrylic acid copolymer coating that provides chewable taste masked characteristics ¹¹.Various inert coating agents like starch, povidone, gelatin, methylcellulose, ethyl cellulose etc. are used for coating drug particles. One of the most efficient methods of drug particle coating is the fluidized bed processor¹². In this approach powder’s as fine as 50μm, are fluidized in expansion chamber by means of heated, high velocity air and the drug particles are coated with a coating solution introduced usually from the top as spray through nozzle. The coated granules are dried with warm air.

3) Taste masking by formation of inclusion complexes:

In inclusion complex formation, the drug molecule fits into the cavity of a complexing agent i.e., the host molecule forming a stable complex. The complexing agent is capable of masking the bitter taste of the drug by either decreasing its oral solubility on ingestion or decreasing the amount of drug particles exposed to taste buds thereby reducing the perception of bitter taste. Vander Waals forces are mainly involved in inclusion complexes. Beta-cyclodextrin is most widely used complexing agent for inclusion type complexes²¹. It is sweet, nontoxic, cyclic oligosaccharide obtained from starch. Strong bitter taste of carbapentane citrate syrup was reduced to approximately 50% by preparing a 1:1 complex with cyclodextrin. The suppression of bitter taste by cyclodextrin was in increasing order of alpha, gamma and beta cyclodextrin²⁰.

4) Molecular complexes of drug with other chemicals:

The solubility and adsorption of drug can be modified by formation of molecular complexes. Consequently lowering drug solubility through molecular complex formation can decrease the intensity of bitterness of drug. Morella and Pitman²² reported that caffeine forms complexes with organic acids that are less soluble than xanthane and as such can be used to decrease the bitter taste of caffeine.

5) Solid Dispersions: They are dispersions of one or more active ingredient in an inert carrier or matrix in solid state and insoluble or bland matrices may be used to mask the taste of bitter drugs²³. Carriers used in solid dispersion systems include povidone, polyethylene glycols, hydroxypropyl methylcellulose, urea, mannitol and ethylcellulose. Various approaches for preparation of solid dispersion are described below.

a) Melting method: In this method, the drug or drug mixture and a carrier are melted together by heating. The melted mixture is cooled and solidified rapidly in an ice bath with vigorous stirring. The final solid mass is crushed and pulverized.

b) Solvent method: In this method, the active drug and carrier are dissolved in a common solvent, followed by solvent evaporation and recovery of the solid dispersion.

6) Microencapsulation:

Microencapsulation process has been defined as a means of applying relatively thin coating to small particles of solid, droplets of liquid and dispersion. This process can be used for masking of bitter tasting drugs Coating agents employed includes gelatin, povidone, hydroxy propyl methylcellulose, ethyl cellulose, bees wax, carnauba wax, acrylics and shellac²⁴. Bitter tasting drugs can first be encapsulated to produce free flowing microcapsules, which can then be blended with other excipients and compressed into tablets. Microencapsulation can be accomplished by variety of methods including air suspension, coacervation, phase separation, spray drying, congealing, pan coating, solvent evaporation and multiorifice centrifugation techniques²⁵. Diclofenac Sodium microcapsules were successfully prepared using a system of ethyl cellulose - toluene - petroleum ether. Tinidazole was microencapsulated within various cellulose polymers like ethyl cellulose, eudragit–L and cellulose acetate phthalate with the final aim to mask its taste without affecting its bioavailability²⁶_.

7) Mass extrusion (Dispersion coating):

This technology involves softening the active blend using the solvent mixture of water-soluble polyethylene glycol, using methanol and expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets. The dried cylinder can also be used to coat granules of bitter tasting drugs and thereby masking their bitter taste.

8) Multiple Emulsions:

A novel technique for taste masking of drugs employing multiple emulsions has been prepared by dissolving drug in the inner aqueous phase of w/o/w emulsion under conditions of good shelf stability. The formulation is designed to release the drug through the oil phase in the presence of gastrointestinal fluid ^{27, 28,}.

9) Using Liposome:

Another way of masking the unpleasant taste of therapeutic agent is to entrap them into liposome. For example, incorporating into a liposomal formulation prepared with egg phosphatidyl choline masked the bitter taste of chloroquine phosphate in HEPES (N-2- hydroxyetylpiperzine-N’- 2- ethane sulfonic acid) buffer at pH 7.2 ²⁹ .

10) Prodrug:

A Prodrug is a chemically modified inert drug precursor, which upon biotransformation liberates the pharmacologically active parent drug. Examples of drug with improved taste are given below ³⁰ (Table-3).

Table 3: Prodrugs with improved taste

Sr. no.	Parent drug	Prodrug with improved taste
1	Chloramphenicol	Palmitate ester
2	Clindamycin	Palmitate ester
3	Triamcinolone	Diacetate ester

11) Formation of Salts or Derivatives:

In this approach, an attempt is made to modify the chemical composition of the drug substance itself, so as to render it less soluble in saliva and thus make it less sensitive to the taste buds. Aspirin tablets can be rendered tasteless by making magnesium salt of aspirin. Dichlorpheniramine maleate is a taste-masked salt of chlorpheniramine. The alkyloxy alkyl Carbonates of Clarithromycin have remarkably alleviated bitterness and improved bioavailability when administered ³¹.

12) Use of Amino Acids and Protein Hydrolysates:

By combining amino acids or their salts with bitter drugs, it is possible to substantially reduce the bitterness. Some of the preferred amino acids include sarcosine, alanine, taurine, glutamic acid and glycine³¹. The taste of ampicillin improved markedly by preparing its granules with glycine and mixing them with additional quantity of glycine, sweeteners, flavors and finally compressing them into tablets ³².

13) Taste-masking by Viscosity Modifications:

Increasing the viscosity with thickening agents such as gums or carbohydrates can lower the diffusion of bitter substances from the saliva to the taste buds. This provides a taste masked liquid preparation for administration of a relatively large amount of unpleasant tasting medicines. The composition of such a formulation comprises a taste masking liquid base with a high viscosity induced by thickening agents such as polyethylene glycol and sodium carboxy methylcellulose³³.

14) Ion Exchange Resin:

Another popular approach in the development of taste masking is based on ion exchange resin. Ion exchange resins are solid and suitably insoluble high molecular weight polyelectrolytes that can exchange their mobile ions of equal charge with the surrounding medium. The resulting ion exchange is reversible and stiochiometric with the displacement of one ionic species by another³⁴ . Synthetic ion exchange resins has been used in pharmacy and medicine for taste masking or controlled release of drug as early as 1950³⁵. Being high molecular weight water insoluble polymers, the resins are not absorbed by the body and are therefore inert. The long-term safety of ion exchange resins, even while ingesting large doses as in the use of cholestyramine to reduce cholesterol has established unique advantage of ion exchange resins is due to the fixed positively or negatively charged functional groups attached to water insoluble polymer backbone. The adsorption of bitter drugs onto synthetic ion exchange resins to achieve taste coverage has been well documented. Ion exchange resins like Amberlite CG 50 was used for taste masking of pseudoephedrine in the chewable Rondec decongestant tablet ³⁶. Antibacterial belonging to quinolone category like ciprofloxacin was loaded on cation exchanger and administered to animals. The taste was improved as animal accepted the material more readily. Binding to a cation exchange resin like Amberlite IRP-69 masked the taste of peripheral vasodilator buflomid. Manek S.P. et al. ³⁷evaluated resins like Indion CRP 244 and CRP 254 as taste masking agents. Some bitter drugs whose taste has been masked by using ion exchange resin are listed in the (Table 4).

Drug release from the resin depends on two factors, the ionic environment (i.e., pH electrolyte concentration) within the GIT and the properties of resin. Drug molecules attached to the resin are released by exchanging with appropriately charged elements in GIT, followed by diffusion of free drug molecule out of resin. The process can be depicted by the following equations 1 and 2 for anion exchange and cation exchange respectively.

Where X and Y are ions in the GIT ³⁸.

Resin + — Drug + X = Resin + —X + Drug ———Eq. 1

Resin + — Drug +Y = Resin + —Y + Drug ————Eq. 2

Ion exchange resin can be classified into four major groups

1. Strong acid cation exchange resin, e.g., Amberlite IRP-69

2. Weak acid cation exchange resin, e.g., Amberlite IRP-65

3. Strong base anion exchange resin, e.g., Amberlite IRP-276

4. Weak base anion exchange resin, e.g., Dimethylamine resin

Ion exchange resins (IER) have received considerable attention from pharmaceutical scientists because of their versatile properties as drug delivery vehicles. In past few years, IER have been extensively studied in the development of novel drug delivery system and other biomedical applications. Several ion exchange resin products for oral and parenteral administration have been developed for immediate release and sustained release purposes. Research over last few years has revealed that IER are equally suitable for drug delivery technologies including controlled release, transdermal, nasal, topical and taste masking.

Table 4: Drug and Ion exchange resins employed to mask bitter taste

Drug	Ion exchange resin
Norfloxacin	Indion 204 (weak cation exchange resin)
Roxithromycin	Indion 204 (weak cation exchange resin)
Ciprofloxacin	Indion 234 (weak cation exchange resin)
Chloroquine phosphate	Indion 234 (weak cation exchange resin)
Buflomedil	Amberlite IRP-69
Chlorepheniramine maleate	Indion CRP-244, IndionCRP-254
Diphenhydramine HCL	Indion CRP-244, IndionCRP-254
Ranitidine Indion-234,	Cation-anion exchange resin

[II Techniques Employed for Taste Masking of Different Dosage Forms:

The drug, i.e., the active pharmaceutical ingredient is finally formulated in a suitable dosage form such as tablet, powder, liquid, etc.

A) Tablets:

Most of the tablets can be effectively masked for their taste by applying inert polymer coatings that prevent the interaction of the drug substance with the taste buds. Nevertheless, attempts have been made time to time by several scientists to investigate and explore the use of newer materials in bad taste abatement and good taste enhancement.

B) Granules or Powder:

Granules for reconstituting as liquids (like sachets, sprinkle capsules and powders) hold a high share of pediatric and geriatric market. A large number of patents on the topic highlight the significance of the same. Thus taste masking of granules becomes an important priority in product development and varied technologies and methodologies exist for the same as illustrated below. Hayward et al.³⁹ have reported a granular composition for taste masking comprising of drug core of a Non Steroidal Anti-Inflammatory Drug (NSAID) and methacrylate ester copolymers as coating agents for taste masking. The method comprises of coating the drug cores with separate layers of aqueous dispersions of the copolymers. Granules of the invention could be used in the preparation of chewable tablets, which had good palatability and bioavailability.

Kishimoto et al.⁴⁰ used mannitol and lactose in different weight ratios (1: 1.5 - 1:5) as coating materials for masking bitter taste of solid drug preparations. Yajima et al.⁴¹ in their patent have described a composition comprising of a drug with unpleasant taste of polymer solution and D-crystals of monoglycerides. Eudragit E (100 g) was dissolved in melted stearic acid monoglyceride (600 g) and then erythromycin (300 g) were added to the mixture to obtain a powder, which was again mixed with sorbitol, magnesium oxide and starch to give taste masked granules of erythromycin.

Danielson et al.⁴² invented a dosage form comprising granules containing the histamine receptor antagonist which are provided with taste masking coating comprising a water insoluble, water permeable methacrylate ester copolymer in which the coating is applied to the granules in an amount which provides a taste masking effect for a relatively short period during which the composition is being chewed by a patient but which allows substantially immediate release of the histamine receptor antagonist after the composition has been chewed and ingested. Kumar et al.⁴³ provided a means and method for manufacturing palatable drug granules using a polymer having at least one free carboxyl group and poly vinyl pyrolidone.

C) Liquids:

They present a major challenge in taste masking because the majority of pediatric preparations are syrups and suspensions although, the aforementioned methodologies have also had been used for improving liquid taste and few patents in this area are worth mentioning. Nakona et al ⁴⁴masked the bitter taste of vitamin B1 derivatives such as dicethimine by formulating with menthol and or polyoxyethylene, polyoxypropylene for formulating oral liquids.

Osugi et al.⁴⁵in their invention subjected oral liquids containing Diclofenac and its salts to heat treatment in the presence of glycine, glycerrhizinic acid or salt thereof to mask the bitter taste and to prevent the irritation of the throat upon oral administration. Meyer et al.⁴⁶used prolamine, applied as single coating in weight ratio 5% to 100% relative to active substance being coated result in the production of a liquid suspension which effectively masked the taste of orally administered drugs which are extremely bitter. Prolamine coating does not restrict the immediate bioavailability of the active substance. Prolamine coating is effective in masking the taste of antibiotics, vitamins, dietary fibers, analgesics, enzymes and hormones. Pharmaceutical composition comprising polyhydric alcohol based carrier to mask the bitter taste of a drug were reported by Swaminathan et al^.⁴⁷who prepared the liquid containing cimetidine, talin, peppermint oil and glycerol. Morella et al. ⁴⁸ invented a liquid suspension of microcapsules taste masked as a function of a polymer coating and the pH of suspended medium at which pharmaceutically active ingredients remain substantially insoluble. Yu et al.⁴⁹ invented a liquid composition comprising a pharmaceutically active medicament coated with a taste masking effective amount of polymer blend of dimethylaminoethyl methacrylate and neutral methacrylic acid ester and a cellulose ester in an aqueous vehicle. The liquid composition utilizes a reverse enteric coating, which is soluble in acid pH of the stomach generally about 1-4 but relatively insoluble at the non-acidic pH of the mouth. The coating provides the rapid release and absorption.

[III] Evaluation of Taste Masking Effect:

Sensory analysis has been used in developed countries for years to characterize flavors, odors, and fragrances. Historically expert provided formulation scientist with subjective data on the composition of one product with another. Nowadays, sensory analysis employs objective or analytical methods and subjective or hedonic method (Table 5). Soutakagi, et al.⁵⁰ invented a multichannel taste sensor whose transducer is composed of several kinds of lipid/polymer membrane with different characteristics, which can detect taste in manner similar to human gustatory sensation. Taste information is transformed into a pattern composed of electrical signals of membrane potential of the receptor part. It was reported that suppression of bitterness of Quinine and a drug substance by sucrose could be quantified by using multi channel taste sensor. The present method can be expected to provide new automated method to measure the strength of drug substance in place of sensory evaluation.

Table 5: Evaluation of taste masking

Subjective Method	Objective Methods
Preference Test	Difference Test
Paired Testing	Paired Difference Test
Triangle Testing	Triangle Difference Test
Hedonic Scale	Duo trio Test
	Ranking Test
	Analytical Test
	Flavor Profile
	Time Intensity Test
	Single attribute test
	Dilution Profile
	Statistical Test

Evaluation of the taste masking effect from coated microsphere can de done by determining the rate of release of the drug from the microsphere. Similarly for evaluating the taste masking effect by ion exchange resin, the drug release rate can serve as an index of the degree of masking achieved. Other methods include evaluation by a trained flavor profile panel and time intensity method in which a sample equivalent to a normal dose was held in mouth for 10 seconds. Bitterness level are recorded immediately and assigned values between 0-3.

CONCLUSION:

Taste masking of bitter drugs has been a challenge to the scientists. We have tried to describe various methods, which are being used for taste masking of bitter drugs. The methods described in this review can be used for bench scale as well as pilot scale also. There are numbers of technologies available, which effectively mask the objectionable taste of drugs but require skillful application. With application of these techniques and proper evaluation of taste masking effect one can improve product to a large extent. Moreover, the development of taste masking methodology requires great technical skill and the need for massive experimentation.

REFERENCE:

1. Glen M. Taste masking in oral pharmaceuticals. Pharm Technol. 18: 1994; 84-98.

2. Sohi H. Sultana Y and Khar RK. Taste masking technologies in oral pharmaceuticals: Recent developments and approaches. Drug Dev Ind Pharm. 30(5); 2004: 429-48.

3. Smith DV, Margolskee RF. Making sense of taste. Scientific America. 34; 2001: 84-86.

4. Schiffman HS. Sensation and Perception: An Integrated Approach. John Wiley and Sons, Canada: 2000; 5th ed. Ontario, pp.163-169.

5. Reilly WJ: Remington: The Science and Practice of Pharmacy, Mack publishing company, 2002; 20^thed: pp.1018-1020.

6. Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics. 1995;1^st ed: pp.162-163,165, 335.

7. Kuchekar BS, Badhan AC and Mahajan HS. Mouth dissolving tablets: A novel drug delivery system, Pharma Times 35; 2003: 7-9.

8. Amita Nanda, R.Kandarapu. An update on taste masking technology for oral pharmaceuticals. Indian J Pharm Sci. 2002: 664-669.

9. Versha B, Pokharkar. Taste masking of pharmaceuticals. Indian J Pharm Sci. April 2005.

10. Mauger JW, Robinson JR, Dennis H. Coating technology for taste masking orally administered bitter drugs. US Patent 5728403 (1998)

11. Davis JD. Drug Cosmet India, Encyclopedia of Pharmaceutical Technology Volume II, 2000.

12. Mendes WR, Anaebonam AO, Daruwala JB, Lachman L, Liberman Ha, Kanig JL. Theory and practice of Industrial . 3^rd ed. 1976 p.346-350.

13. Kaneko K. Kanada K, Yamada T, Saho N, Ozer T.Yuasa H and Kanaya Y. Chem Pharm Bull. 45; 1997:1061-1063.

14. Bodmeier R, Chen H, Tyle P, and Jarose P. An update on taste masking technologies for oral pharmaceuticals. J control release. 15;1991: 65-68.

15. Bianchini R, Bruni G, Gazzaniga A and Vecchio C. An update on taste masking technologies for oral pharmaceuticals. Drug Develop Ind Pharma. 19; 1993: 2021-2023.

16. Lorenzo- Lamasa ML, Cuna M, Vila-Jato JL, Torres D, and Alonso ML. Development of a microencapsulated form of Cefuroxime axetil using pH-sensitive acrylic polymers. J Microencap. 14: 1997; 607-610.

17. Friend DR. Taste masking of bitter drug powder without loss of bioavailability by heat treatment of wax- coated microparticles. J Microencap.1992: 469-472.

18. Ozer AY and Hincal AA. Fast dissolving drug delivery system: an update. J Microencap. 7; 1990: 327-330.

19. Ishikawa T, Watanabe SD, Utoguchi NM. Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter taste masked granules by compression method. Chem Pharm Bull. 47; 1999:1451-1454.

20. Sugao H, Yamazakis, Yhiozava H. and Yano K. Taste masking of bitter drug powder without loss of bioavailability by heat treatment of wax-coated microparticles. J Pharm Sci. 87; 1998: 96-99.

21. Szejili J, Szente L, Elimination of bitter, disgusting taste of drugs and foods by cyclodextrins. Eur J Pharm Biopharm. 2005; 61(3):115-122.

22. Morella A.M., Pitman IH. Heinicke GW. Taste masked liquid suspensions.US Patent No 6197348 (2001)

23. Lachman L. Theory and practice of Industrial pharmacy.1986; 3^rd ed: pp. 450-454.

24. Liberman HA, Lachman L. Pharmaceutical Dosage Forms, Tablet Volume I. 1989; 11-14, 136, 198-199, 210- 212, 99-101, 159-160.

25. Bakan JA. Capsule part III, Microencapsulation, Theory and Practice of Industrial Pharmacy. 1986; 3^rd ed: pp. 412-429.

26. Kshiersagar SJ and Pokharakar VB. Taste masking of tinidazole and optimization of microencapsulation method. URL: http://www.pharmainfo.net/May 2006.

27. Rao MY and Bader F. Masking the taste of chloroquine by multiple emulsion. The East Pharm. 1993: 123-125.

28. Rosoff M. Pharmaceutical dosage form: disperse system. Vol I 1969; p.59-60.

29. Kasturagi Y, Sugiura YC, Lee K, Otsugi and Kurihara. Selective Inhibition of Bitter Taste of Various Drugs by Lipoprotein. Pharm Res. 12: 1995; 658-662.

30. Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics. 1995; 1^st ed: pp. 335,162-163,165.

31. Roy GM. Taste masking in oral pharmaceuticals. Pharm Tech. 1994:62-67.

32. Meyer GA and Mazer TB. Taste masking technologies in oral pharmaceuticals: Recent developments and approaches. U.S.Patent 5599556, 1997.

33. Skrabanja. Taste masking compositions comprising spray dried microcapsules. U.S. Patent 6040301, 2000.

34. Swarbik J. Ion exchange resins and sustained release; Encyclopedia of Pharmaceutical Technology. Vol-8: 2003; 203-217.

35. Dorfner K. Ion exchanger properties and applications. Ann Arbor Science Publisher.1972; 3^rd ed: pp. 2-10.

36. Jain NK. Advances in controlled and novel drug delivery. 2001; 1^st ed: pp. 209-306.

37. Manek SP, Kamat VS. A review on taste masking methods for bitter drug. Indian J Pharm Sci. 43; 1981: 209-212.

38. Agarwal R, Mittal R. Studies on ion exchange resin complex of Chloroquineb Phosphate. Drug Develop Ind Pharm 27: 2001; 359-364.

39. Hayward M. Taste masking of pharmaceuticals. U.S. Patent 37277, 1998; 36-38.

40. Kishimoto A, Okamoto K. Taste masking of Pharmaceuticals. Japan Patent 09143100, 1997.

41. Yajina T, Ishii K, Itai S, Nemoto M, Sultake K, Tukui N. Taste masking of pharmaceuticals. PCT. Inl. Appl. WO 963428, 19.

42. Danielson D W, Shah SA. Taste masking of pharmaceuticals. U.S. Patent 6, 270807.

43. Kumar V. Taste masking of pharmaceuticals. U.S. Patent 6, 372, 259, 2002: Liquids 40-46.

44. Nakano H, Hasegawa K. Taste masking of pharmaceuticals. Japan Patent 11139992, 1999; 41-48.

45. Osugi T. Taste masking of pharmaceuticals. Japan Patent 11139970, 199942.

46. Meyer G, Mazer T. Taste masking of pharmaceuticals U.S. Patent 5599556, 1997.

47. Swaminathan K, Subramania S, Harding R. Taste masking of pharmaceuticals. Wo 9733621, 1997.

48. Morella A, Mario P, Hamilton Heinicke G. Taste masking of pharmaceuticals. U.S. Patent 6197348, 2001.

49. Yu D, Roche E. Taste masking of pharmaceuticals. U.S. Patent 6586012, 2003.

50. Soutakagi KT, Koichiwada HY, Kenzo T. Taste masking of Pharmaceuticals. J Pharm Sci. 87: 1998; 552-559.

Received on 20.06.2011 Modified on 29.06.2011

Research J. Pharm. and Tech. 4(10): Oct. 2011; Page 1513-1518

Drug	Technique	Polymer used
Pseudoephedrine (Antihistaminic)	Emulsion-solvent evaporation (ESE)	Eudragit E ¹³
D-Indobufin(Inhibiter of platelet aggregation)	Fluidized bed drying (FBD)	Eudragit E-100, RS/RLEthyl Cellulose ¹⁴
Clarithromycin (Antibiotic)	Phase separation-coacervation.	Eudragit E-100 ¹⁵
Cefuroxime axetil(Antibiotic)	Emulsion-solvent evaporation (ESE)	Eudragit E-100Eudragit L-100, Eudragit RL-100 ¹⁶
Beclamide(Antiepileptic)	Phase separation-coacervation.	Gelatin¹⁷
Ranitidine (Antiulcer)	Emulsion-nonsolvent evaporation (ENSE)	PEG, Ethyl Cellulose ¹⁸
Oxybutinin(Antihistaminic)	Dispersion coating	Eudragit E-100^{. 19}
Indeloxazine(Cerebral activator)	Fluidized bed drying (FBD)	Hydrogenated oils and surfactants²⁰