A Review On Taste Masking Methods For Bitter Drug

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V.K.Chatap

V.K.Chatap

Undesirable taste is one of several important formulation problems that are encountered with certain drugs The problem of bitter and obnoxious taste of is a challenge to the pharmacist in the present scenario.

Several oral pharmaceuticals and bulking agents have unpleasant, bitter-tasting components. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This paper reviews different methods are available to mask undesirable taste of the drugs, with the applications. Popular approaches in the development of taste masking are based on coating, solid dispersion system and ion exchange resin.

Introduction: -

There are numerous pharmaceuticals that contain actives, which are bitter in taste. With respect to OTC preparations, such as cough and cold syrups, the bitterness of the preparation leads to lack of patient compliance. The problem of bitter and obnoxious taste of drug in pediatric and geriatric formulations is a challenge to the pharmacist in the present scenario. In order to ensure patient compliance bitterness masking becomes essential. Molecule interacts with taste receptor on the tongue to give bitter, sweet or other taste sensation, when they dissolve in saliva. 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. 1

Two approaches are commonly utilized to overcome bad taste of the drug.2 The first includes reduction of drug solubility in saliva, where a balance between reduced solubility and bioavailability must be achieved. Another approach is to alter the ability of the drug to interact with taste receptor. An ideal taste masking process and formulation should have the following properties.3

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.

Methods Of Taste Masking

Various methods are available to mask undesirable taste of the drugs. Some of these are as given below.

Coating of drug particles with inert agents

Coating is an extremely useful technique for number of applications in the pharmaceutical field. 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.4 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.5

Various inert coating agents like starch; povidone, gelatin, methylcellulose, ethyl cellulose etc. are used for coating drug particles. One of the most efficient method of drug particle coating is the fluidized bed processor. 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 .6

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.7

Beta-cyclodextrin is most widely used complexing agent for inclusion type complexes. It is sweet, nontoxic, cyclic oligosacchride obtained from starch. Strong bitter taste of carbapentane citrate syrup was reduced to approximately 50% by preparing a 1:1 complex with cyclodextrin.8 The suppression of bitter taste by cyclodextrin was in increasing order of alpha, gamma, beta cyclodextrin.

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. Higuchi and Pitman,9 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.8

Solid dispersion system

Solid dispersion have been defined as dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by melting (fusion) solvent or melting solvent method.10 Solid dispersion is also called as co precipitates for those preparation obtained by solvent method such as co precipitates of sulphathiazale and povidone. Solid dispersions using insoluble matrices or bland matrices may be used to mask the bitter taste of drugs. Also using them as absorbates on various carriers may increase the stability of certain drugs.

Microencapsulation

Microencapsulation as a process has been defined by Bokan 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 microencapsulating drug particles with various coating agents. Coating agents employed includes gelatin, povidone, HPMC, ethyl cellulose, Bees wax, carnauba wax, acrylics and shellac. 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 and congealing, pan coating, solvent evaporation and multiorifice centrifugation techniques.11

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.12,13

Using Liposome’s

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 7.2.14

Prodrugs

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.2

Table no.2: Prodrugs with improved taste

Sr. no.

Parent drug

Prodrug with improved taste

1

Chloramphenicol

Palmitate ester

2

Clindamycin

Palmitate ester

3

Triamcinolone

Diacetate ester

Mass extrusion method (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.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 another.15 Synthetic ion exchange resin have been used in pharmacy and medicine for taste masking or controlled release of drug as early as 1950.16,17

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 cholesterol17 is 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 psedoephedrin in the chewable Rondec decongestant tablet.17

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.18 Binding to a cation exchange resin like Amberlite IRP-69 masked the taste of peripheral vasodilator buflomid. Manek S.P.et al. evaluated 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 no.3.

Table No.3: Bitter Drugs masked by ion exchange resin

Drug

Ion exchange resin

Norfloxacin

Indion 204 (weak cation exchange resin)

Ciprofloxacin

Indion 234 (weak cation exchange resin)

Roxithromycin

Indion 204 (weak cation exchange resin)

Chloroquine phosphate

Indion 234 (weak cation exchange 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 peroral 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.

Conclusion: -

Taste masking of bitter drugs has been a challenge to the scientist. We have made an attempt to describe various methods, which could be suitable for taste masking of bitter drugs. The methods described in this review can be used for bench scale as well as pilot scale also.

References:

  1. Reilly W.J.; Remington: The Science and Practice of Pharmacy, 20th edition, Mack publishing company, 2002, PP 1018-1020.
  2. Brahmankar D.M., Jaiswal S.B., “Biopharmaceutics & Pharmaceutics”; First Edition; 1995, PP 335,162-163,165
  3. Kuchekar B.S., Badhan A.C.and Mahajan H.S. “Mouth Dissolving Tablets: A Novel Drug Delivery System”, Pharma Times, 2003,35, 7-9.
  4. Mauger J.W., Robinson J.R.and Dennis H., US Patent, 1998, 5,728,403
  5. Shen R.W., US Patent, 1996, 5,552152
  6. Davis J.d.; Drug Cosmet. India; Encyclopedia of Pharmaceutical Technology, Volume II (2000).
  7. Mendes W.R., Anaebonam A.O.and Daruwala J.B., In, Lachman L., Liberman H.A. and Kanig J.L., Theory and Practice of Industrial Pharmacy, Third Edition, 1976, PP 346,
  8. Kurusumi, T., Imamori, K.and Isawa, A., Japan Patent, 1991,03236616
  9. Lachman, L.; “ Theory and practice of Industrial pharmacy”; Third Edition, 1986, PP 450
  10. Liberman, H.A., Lachman, L., “Pharmaceutical Dosage Forms, Tablet Volume I, 1989, PP 11-14, 136, 198-199, 210- 212, 99-101, 159-160.
  11. Bakan, J.A.; Capsule part III, Microencapsulation, Theory and Practice of Industrial Pharmacy, Third Edition, 1986, PP 412-429.
  12. Rao, M.Y.and Bader,F., “ Masking the Taste of Chloroquine by Multiple Emulsion,” The East. Pharm, 1993, 123, (11).
  13. Manek, S.P.; Kamat, V.S.; Indian Journal of Pharmaceutical Science; 1981, 43, 209-212.
  14. Kasturagi, Y., Sugiura, Y.C., Lee, K., Otsugi, and Kurihara, “Selective Inhibition of Bitter Taste of Various Drugs By Lipoprotein.”, Pharm. Res., 1995, 12,5, 658-662.
  15. Swarbik,J.; Ion Exchange Resins And Sustained Release; Encyclopedia Of Pharmaceutical Technology, Vol-8, 2003, 203-217.
  16. Dorfner, K. “ Ion Exchanger Properties and Applications” Third Edition, Ann Arbor Science Publisher, 1972, 2.
  17. Jain, N.K.; “Advances in Controlled and Novel Drug Delivery”, First Edition, 2001, PP 290-306.
  18. Borodkin, S.; Yonker, M.H.; Journal of Pharmaceutical Sciences; 1970, 59(40), 481.
  19. Sambhaji Pisal, Ranna Zainnudin, Praddin Nalawade, Kakasaheb Mahadik and Shivajirao Kadam. “ Molecular Properties of Ciprofloxacin Indion 234 Complexes”, AAPS Pharm.Sci.Tech, 2004 ;5(4).

About Authors:

V.K.Chatap

V. K.Chatap

M. Pharm, Lecturer, Dept. of Pharmaceutics,B.R. Nahata College of Pharmacy (BRNSS Contract Research Center)
P.B. No.6, Mhow-Neemuch Road, Mandsaur, 458001 (India)
Mob: 09300933017, Fax: 07422-255504,E-mail: Chatap@rediffmail.com

Dr. V. B. Gupta

Dr. V. B. Gupta

Professor & Director, B R Nahata College of Pharmacy,(Additional Designation: Director BRNSS Contract Research Center), P B No. 6, Mhow-Neemuch Road, MANDSAUR (MP) 458001 , Tel: 07422-255734, Fax: 07422-255504, Mobile: 09826774144, E-mail: vbgupta@hotmail.com
Web: http://www.brncop.org/bio-data.pdf

D. K. Sharma

D. K. Sharma

M. Pharm. (Ph.D), Reader & Head, Dept. of Pharmaceutics,B.R. Nahata College of Pharmacy (BRNSS Contract Research Center)
P.B. No.6, Mhow-Neemuch Road, Mandsaur, 458001 (India) , Mob: 09827374668, E-mail: dineshsharma1973@rediffmail.com

T. D. Nandgude

M. Pharm (Pharmaceutics), Project Assistant, Academia-Industry Interaction Project – www.aiip.info
(NSTMIS, Department of Science & Technology, Govt. of India.)
B.R. Nahata College of Pharmacy (BRNSS Contract Research Center)
P.B. No.6, Mhow-Neemuch Road, Mandsaur, 458001 (India)
Mob: 09926878701, E-mail: tanajinandgude@gmail.com , aiip@rediffmail.com

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