RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA
4TH ‘T’ BLOCK, JAYANAGAR, BANGALORE - 560 041

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. Name of the Candidate and YASMEEN TAJ

Address #418, NEW LINES, LINDEN STREET,
YELLAGUNDA PALLIYAM,
AUSTIN TOWN,
BANGALORE-560047.
KARNATAKA, INDIA.

2. Name of the Institution AL-AMEEN COLLEGE OF PHARMACY,

HOSUR ROAD,
OPP. LALBAGH MAIN GATE,
BANGALORE – 560 027.
KARNATAKA.

3. Course of Study and Subject M. PHARM – PHARMACEUTICS

4. JUNE-2009
Date of Admission

5. Title of the Topic:

“FORMULATION AND EVALUATION OF TASTE MASKED ORALLY

DISINTEGRATING TABLETS FOR PAEDIATRIC POPULATION”.

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6.0 Brief resume of the intended work:

6.1 – Need for the study

Bronchitis is a respiratory disease in which the mucous membrane of the bronchial
passages in the lungs become inflammed. As the irritated membrane swells and grows
thicker, it narrows or shuts off the airways in the lungs, resulting in coughing spells
accompanied by thick phlegm and breathlessness. The disease occurs in two forms;
acute (lasting less than 6 weeks) and chronic (reoccurs frequently for more than 2
years). Acute bronchitis is very common in children and is generally caused by lung
infection.[1]

Bronchiectasis is a persistent irreversible dilation and distortion of medium sized

bronchi. It is a lung condition that usually develops after a series of lung problems, a
lot of mucous collects in the lungs causing discomfort and needs to cough it up. The
mucous (phlegm) also collects bacteria, which can add to breathing difficulties.
Patients diagnosed with bronchiectasis frequently have difficulty in expectorating the
infected sputum.[2]

People with chronic bronchitis may experience recurrent exacerbations with

worsening symptoms or greater volume or purulence of sputum. These exacerbations
contribute to poorer health. Bronchitis is most common disease of childhood.

The drugs commonly used to treat bronchitis and bronchiectasis are called as
mucolytics and expectorants. A mucolytic agent or expectorant is any agent which
dissolves thick mucous and is usually used to help relieve respiratory difficulties.

The drugs include Dextromethorphen, Guiafenesin, Dexbrompheniramine,

Pseudoephedrine, Bromhexine, Ambroxol hydrochloride, acetylcysteine, carbocisteine.

An allergy is a condition characterized by a level of sensitivity greater than normal

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to a specific substance or a group of substances. These substances are called as
allergens, trigger a response in susceptible individuals. These produce powerful
chemicals like histamine, which cause inflammation. These chemicals act on tissues in
various parts of the body, such as the respiratory system and cause symptoms of allergy
like sneezing often with running and clogged nose, coughing and postnasal drip,
itching eyes, nose and throat.[3]

Anti-histaminic drugs like cetrizine dihydrochloride are commonly used for

treatment of allergy. Cetrizine is a potent H 1 receptor antagonist without any significant
anticholinergic and antiserotonin effects. It inhibits the histamine mediated early phase
of allergic reactions, also provides a protective effect from bronchospasm induced by
inhaled histamine in asthamatics.

Combination approach of Ambroxol hydrochloride and Cetrizine dihydrochloride

is carried out as taking one tablet is preffered over two, also it reduces the symptoms of
allergy and cough at once and improves patient compliance especially in case of
paediatric population.

More than 50 percent of the pharmaceutical products are orally administered as it

is the most convenient route of administration and undesirable taste is one of the
important formulation problem encountered with oral products. The taste of oral
pharmaceutical product is an important parameter for governing compliance. Thus,
taste masking of oral pharmaceutical products is important tool to improve patient
compliance and quality of treatment especially in paediatrics.[4]

Most of the drugs used as Mucolytic and Anti-histaminics are bitter in taste,
therefore are not favourable as oral dosage form especially for paediatric population.
Undesirable taste is one of the several important formulation problems that are
encountered with certain drugs. The problem of bitter and obnoxious taste of drugs is a
challenge in the present scenario.

There always exists a difference between adult and paediatric taste preferences.
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Children are found to be objectionable to bitterness, hence before formulating a
paediatric medicine one should be aware of children’s taste preferences. Its quiet
obvious that the oral dosage forms expose the drug in the mouth, a bad tasting
formulation has poor patient compliance. Thus the product taste directly influences the
willingness of a child to take medicine repeatedly. To deal with these taste issues, taste
masking of the bad tasting active ingredient has become utmost important factor in
paediatric formulations.[5]

The active pharmaceutical ingredient chosen for the present study are Ambroxol
hydrochloride which has a daily dose of 60-120mg in 2 or 3 divided doses and
Cetrizine dihydrochloride, given in 10mg dose.

Literature reveals that Ambroxol hydrochloride is a highly bitter molecule and

even cetrizine dihydrochloride is bitter in taste. Also only one syrup dosage form is
available with the combination of Ambroxol hydrochloride and Cetrizine
dihydrochloride. Thus there is a need to develop an efficiently taste masking
formulation of this combination. Moreover it is observed that along with commonly
used taste masking and sweetening agents, Eudragit polymers are gaining importance
in masking the taste of drugs. Eudragit EPO is used for effective taste masking of few
drugs like Quinine sulphate, Ondansetron hydrochloride, Lornoxicam, Valdecoxib.

Over the past three decades, Orally Disintegrating Tablets (ODT) have gained
much attention as a prepared alternative to the conventional oral dosage forms such as
tablets and capsules. Generally, the ODT’s are formulated to disperse rapidly in the
mouth, enabling medication to be swallowed without water, thereby increasing
convenience and compliance across the broad range of indications and patient types.
Orally Disintegrating tablets are gaining popularity as paediatric formulation.

The most significant issue with the Orally Disintegrating Tablet is the bitterness of
the drug that can be exposed as the tablet breaks apart. Poor taste can negate the
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benefits of the Orally Disintegrating Tablet and lead to patient non compliance as the
tablet dissolves or disintegrates in the mouth in close proximity to the taste buds.
Hence to deal with these taste issues, masking of bad tasting drug is very important in
an Orally Disintegrating Tablet formulation.

By designing these commonly used molecules( Ambroxol hydrochloride and

Cetrizine dihydrochloride) in combination into an effectively taste masked Orally
Disintegrating Tablet formulation, an attempt will be made to obtain the most
acceptable dosage form for paediatric population.

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6.2 REVIEW OF LITERATURE

 Ambroxol is a clinically proven systemically active mucolytic agent. When

administered orally onset of action occurs after about 30 minutes. The
breakdown of acid mucopolysaccharide fibers makes the sputum thinner and
less viscous and therefore more easily removed by coughing.[1]

 Ambroxol is an active substance with a long history that influences

parameters considered to be the basis for the physiological production and
the transport of the bronchial mucus. Therefore Ambroxol’s indication
‘secretolytic therapy in an acute and chronic pulmonary disease associated
with abnormal mucous secretion and impaired mucous transport.[2]

 Gawade RS, Ravinder k. Cetrizine is used in commercial products as a

dihydrochloride salt. It is a piperazine derivative and a metabolite of
hydroxyzine, is an orally active, selective H-1 receptor antagonist and useful
as non-sedating antihistaminic. Cetrizine dihydrochloride is bitter in taste
and is reported to long acting, used for symptomatic relief of allergic
conditions.[3]

 Basak SC,.et al. reviewed that ambroxol, a metabolite of bromhexine is used

as an expectoration improver and a mucolytic agent. It is used in the
treatment of acute and chronic disorders characterized by the production of
excess of mucous. It is been successfully used for decades in the form of its
hydrochloride salt as a secretion releasing expectorant in a variety of
respiratory disorders.[6]

 Venkatesh DP, Geetha Rao CG. presented that amroxol hydrochloride, is a

potent mucolytic capable of inducing bronchial secretion. It is used the
treatment of asthma, bronchitis and cough, but it is very bitter and slightly
soluble in water, therefore its taste masking is important to omprove patient
compliance and the quality of treatment especially in paediatrics.[7]

 Jacob S, Shirwaikar A. studied that taste masking is an important

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8.0 BIBLIOGRAPHY

1. http://www.drugs.com/ambroxol.html [cited 2009 Nov 11]

2. Crockett A, Cranston JM, Alpers JH, Latiner KM. Mucolytics for bronchiectasis;
cocrane database of systemic reviews 2001;(1).art no:CD001289.

3. http://www.freshpatents.com//cetrizinecompositions [cited 2009 Nov 12]

4. http://malerba@medunibs.it/ambroxol.htm [cited 2009 Nov 12]

5. http://americanpharmaceuticalreview.com [cited 2009 Nov 14]

6. Basak.SC, Reddy BMJ, Lucas mani KP. Formulation and release behaviour of
sustained release ambroxol hydrochloride HPMC matrix tablets. Indian J Pharm
Sci 2006;68(5):594-8.

7. Venkatesh DP, Geetha Rao CG. Formulation of taste masked oro-dispersible

tablets of ambroxol hydrochloride. Asian J Pharm 2008;2(4):261-4.

8. Jacob S, Shirwaikar A. Preparation and evaluation of microencapsulated fast melt

tablets of ambroxol hydrochloride. Indian J Pharm Sci 2009;71(3):276-84.

9. Bhatia NM, Ganbavale SK, More HN. Spectrophotometric estimation of ambroxol

hydrochloride and cetirizine hydrochloride in tablets. Asian J Pharm
2008;2(3):159-62.

10. Kayumba C, Huydebaert N, Cordella C, Vervaet C, Remon JP. Quinine sulphate

pellets for flexible pediatric drug dosing; formulation development and evaluation
of taste masked efficiency using electronic tongue. Eur J Pharm Biopharm
2007;66(3):460-65.

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11. Khan S, Kataria P, Nakhat P, Yeole p. Taste masking of
ondensetron hydrochloride by polymer carrier system and
formulation of rapid disintegrating tablets. AAPS PharmSciTech
2007;8(2):E1-E7.

12. Okuda Y, Osawa T. A new formulation to orally disintegrating

tablets using a suspension spray coating method. Int J Pharm Sci
2009;382(2):80-87.

13. http://www.iptonline.com/articles/public/rohm1.pdf [cited 2009

nov 23]

14. http://www.emedicinehealth.com/bronchitis/article_em.htm [cited 2009 Nov 15]

15. http://en.wikipedia.org/wiki/mucolytics_agent [cited 2009 Nov 16]

16. Poole PJ, Black PN. Oral mucolytics for exacerbation of chronic pulmonary
disease: systemic review. BMJ 2001;322(7297):1271.

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9.0 SIGNATURE OF THE CANDIDATE:
(YASMEEN TAJ)

10.0 REMARKS OF THE GUIDE: Recommended for Approval

11.0 NAME AND DESIGNATION OF:

11.1 INSTITUTIONAL GUIDE: Dr. (Mrs.) ROOPA S. PAI

PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
AL-AMEEN COLLEGE OF PHARMACY,
BANGALORE-560027.

11.2 SIGNATURE:

Dr. (Mrs) V. KUSUM DEVI

11.3 CO-GUIDE
PROFESSOR AND HEAD,
DEPARTMENT OF PHARMACEUTICAL
MARKETING AND MANAGEMENT,
AL-AMEEN COLLEGE OF PHARMACY,
BANGALORE-560027.

11.4 SIGNATURE:

Dr. (Mrs.) SARASIJA SURESH

11.5 HEAD OF THE PROFESSOR AND HEAD,
DEPARTMENT DEPARTMENT OF PHARMACEUTICS,
AL-AMEEN COLLEGE OF PHARMACY,
BANGALORE-560027.

11.6 SIGNATURE:

12.0 12.1 REMARKS OF THE

CHAIRMAN AND PRINCIPAL Forwarded to the University for Scrutiny

12.2 SIGNATURE OF THE

PRINCIPAL
PROF. B. G. SHIVANANDA
Principal,
AL-AMEEN COLLEGE OF PHARMACY,
HOSUR ROAD,
BANGALORE – 560 027.
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