“FORMULATION AND EVALUATION OF TASTE MASKING TECHNOLOGIES FOR AN ANTIBIOTIC”
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
KAPURIYA NILAY SURESHBHAI
I M.PHARM
DEPARTMENT OF PHARMACEUTICS
VISVESWARAPURA INSTITUTE OF PHARMACEUTICAL SCIENCES
BANGALORE – 560070
(2009-2010)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
1 /NAME OF THE CANDIDATE AND ADDRESS
/ KAPURIYA NILAY SURESHBHAI#396, TOP FLOOR, 5th MAIN ROAD
NAGENDRA BLOCK,
HANUMANTHNAGAR,
BANGALORE-560050.
2 /
NAME OF THE INSTITUTION
/ VISVESWARAPURA INSTITUTE OF PHARMACEUTICAL SCIENCESBANGALORE – 560070
3 /
COURSE OF STUDY AND SUBJECT
/ MASTER OF PHARMACY INPHARMACEUTICS
4 /DATE OF ADMISSION
/ 12 – 06 – 20095 /
TITLE OF THE TOPIC:
“FORMULATION AND EVALUATION OF TASTE MASKING TECHNOLOGIES FOR AN ANTIBIOTIC”Page 1 of 9
6 / BRIEF RESUME OF THE INTENDED WORK:6.1 NEED FOR THE STUDY:
Antibiotics are among the most frequently prescribed medications in modern medicine. Antibiotics are used to treat a wide range of infections like respiratory tract infection, urinary tract infection, soft tissue infection, useful in prophylaxis of patients undergoing surgery, in curing gonorrhea, as well as effective in treatment of typhoid, etc. Most of the antibiotics are bitter in taste and resulting in patient noncompliance while administering.
Novel drug delivery technologies are revolutionizing drug discovery and development. The challenge in the area of drug delivery is to deliver both existing and emerging drug technologies in a manner that benefits patients.
Good mouth feel of formulation helps to change the basic view of medication from “bitter pill” to “better pill”. Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that is 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. Also, such pharmaceutical preparations used for elderly patients have been investigated to improve the treatment compliance and quality of life of such patients. Thus, the problem of bitter and obnoxious taste of drug in pediatric and geriatric formulations is a challenge to the pharmacist in the present scenario.
Patient expects the oral dosage form to be pleasantly flavored and palatable. This change in patient attitude is due to the advances made by flavoring and pharmaceutical industries. Several oral pharmaceuticals and bulking agents have unpleasant, bitter‐tasting components. Thus, any pharmaceutical formulation with a pleasant taste would definitely be preferred over another product and would translate into better patient compliance and therapeutic value. The desire of improved palatability in these products has prompted the development of numerous formulations with improved aesthetic appearance and performance.
The application of drug delivery technology to any molecule is based on market needs, product differentiation, and patient compliance. The time to get the new chemical entity to the market eats up a majority of the patent life cycle of the drug. Taste masking technologies are very helpful in adding value/timeline to the patent.10
6.2 REVIEW OF THE LITERATURE:
1. The bitter taste of drugs, food components, and any other substances which get in the mouth, dissolved in an aqueous solution, or in the saliva, can be strongly reduced or fully eliminated, if the bitter component forms an inclusion complex with an appropriate cyclodextrin. The bitter drug is complexed and hence it cannot react with the taste buds in the buccal cavity, resulting in a palatable formulation.1
2. Although tablets and capsules constitute a major portion of the drug delivery systems, some patient groups, such as pediatrics, geriatrics, and bedridden or disabled patients, may have difficulties in swallowing tablets or capsules. To meet these medical needs, formulators have devoted considerable efforts to develop a novel dosage form known as orally disintegrating tablet, which can disintegrate rapidly in the saliva without water. The first is to mask the distasteful sensation by the addition of flavors, sweeteners and effervescent agents. The second is to avoid the bitter drugs coming into direct contact with patients’ taste buds by coating or granulation.7
3. Bitter taste of ofloxacin was taste masked with two methods. One method included addition of aspartame as sweetener and sodium starch glycolate as disintegrant with isopropyl alcohol as granulating agent, while other method included mass extrusion using Eudragit E100 as taste masking agent along with Avicel PH 102 and ethanol. Formulation having drug and polymer ratio of 1: 4 were optimized with 98% drug release after 15 min in pH 1.2 buffer. Stability studies were carried out according to ICH guidelines for period of 30 days.3
4. Numbness masking is key technology for the manufacturing of multiparticulate dosage forms of drugs causing numbness. Numbness induced by drugs affects both the oral cavity and the esophagus. A “salting-out taste-masking system” is a multiparticulate system consisting of a drug core, a salting-out layer containing salts and water soluble polymers, and a water penetration control layer containing water insoluble materials. The system generates a long lag time for numbness masking. In this study, sodium carbonate and hydroxypropylmethylcellulose were used as the salt and water-soluble polymer in the salting-out layer, respectively.2
5. Many drugs including alkaloids such as quinine or berberine and antibiotics such as sparfloxacin and clarithromycin exhibit bitter taste when orally administered. For patients, such drugs are not necessarily easy to swallow, resulting in non-compliance and subsequent decrease in efficacy. Therefore, various techniques have been examined for improving the problems of the bitter taste. Coating with polymers, microencapsulation, complexation, and chemical modification have been reported. Various formulations with matrix bases and corrigents were examined for development of oral chewable tablets which suppressed the bitter taste of acetaminophen. The bitter taste intensity was evaluated using volunteers by comparison of test samples with standard solutions containing quinine at various concentrations.4
6. The quinolone antibacterial gatifloxacin was adequately taste masked so that it could be utilized for pediatric formulations. A crystalline co-precipitate of gatifloxacin and one or both of stearic acid and palmitic acid in a narrow weight ratio had been found to effectively mask the bitter taste of gatifloxacin. The taste of gatifloxacin was effectively masked in the mouth and in aqueous suspension through a full dosage cycle, typically fourteen days.5
7. Stearic acid microspheres may be used as a means of taste-masking unpalatable drugs, particularly for administration to children. This approach has been used for the formulation of an antibiotic cefuroxime axetil, where the drug particles are coated via a spray chilling process to produce stearic acid coated cefuroxime axetil. This material is subsequently formulated as a suspension which has been shown to exhibit favorable taste masking properties.6
8. Quinine sulphate, an antimalarial agent, is extremely bitter in taste. Taste masked resinates of quinine sulphate were developed using ion-exchange resin. The taste masked complex was then formulated into a prototype suspension base. Taste evaluation of the suspension showed complete masking of the bitterness of the drug. In vitro release studies revealed complete drug elution from the complex after a period of 30 minutes in pH 1.2 buffer.8
9. In most cases, children are affected who often refuse the oral uptake of sodium benzoate as a powder or in solution due to its bad taste. Therefore, small sized, saliva-resistant microcapsules have been developed containing high doses of the drug substance. Granules were produced by roller compacting of sodium benzoate powder without any additives, by solvent free cold extrusion and hot melt extrusion techniques. The granules with a diameter of less than 1 mm were film coated by an ethanolic solution of Eudragit® E 100. The bad taste of sodium benzoate was not recognized in the buccal cavity for at least 5 minutes.9
10. Usually, chemical or technological operations are used to mask the taste of unpleasant tasting drugs. For such drugs to reduce the development cost of formulation, a new approach was considered which does not require, which does not require the modification of the existing formulation or the use of additional costly technological operations. Different particle size fractions of two unpleasant tasting drugs (niflumic acid and ibuprofen) were blended in binary mixes with different particle size fractions of two non tasting excipients (ethyl cellulose and hydroxypropyl methylcellulose).11
11. Sporopollenin exines extracted from the spores of the plant Lycopodium clavatum were used to encapsulate sunflower oil and of cod liver oil. The encapsulated oils were in the form of a fine powder up to an oil loading of 1/1 (w/w). Sporopollenin exines can be loaded highly, at up to 1 g oil to 1 g of the exines, and still remain as a dry powder and retain flavor masking, thus disguising the contents.12
6.3 OBJECTIVE OF THE STUDY:
The objective of the present study are as follows:
· To mask the bitter taste of an antibiotic drug.
· To check the feasibility of incorporating the taste masked complex into a palatable formulation.
· To evaluate the optimized formulation for various quality control parameters.
· To carry out stability studies according to ICH guidelines for the optimized formulation.
7
8 / MATERIALS AND METHODS:
7.1 SOURCE OF DATA:
The data will be obtained from the experimental work, which includes:
a. Literature survey.
b. Internet search.
c. Text books.
d. Journals.
7.2 METHOD OF COLLECTION OF DATA:
The data will be collected from the prepared formulation, in vitro and in vivo evaluation and stability studies various standard books, journals & other sources like research literature data bases such as science direct and laboratory experiments, etc.
7.3 MATERIALS:
· DRUG: Antibiotic.
· METHOD: Various techniques would be explored for taste masking like addition of flavors and polymers, microencapsulation, etc.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS
TO BE TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR
ANIMALS?
YES
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR
INSTITUTION IN CASE OF 7.3?
Applied to human ethical committee for clearance.
7.4 PLACE OF THE STUDY:
VISVESWARAPURA INSTITUTE OF PHARMACEUTICAL SCIENCES
BANGALORE – 560070.
LIST OF REFERENCES:
1. Szejtli J, Szente L. Elimination of bitter, disgusting tastes of drugs and foods by Cyclodextrins. Eur J Pharm Biopharm 2005 13 May;61:115-25.2. Yoshida T, Tasaki H, Maeda A, Katsuma M, Kazuhiro Sako TU. Mechanism of controlled drug release from a salting-out taste-masking system. J control release 2008 16 July 2008;131:47-53.
3. Dandagi PM, Sreenivasa SA, Manvi FV, Patil MB, Mastiholimath VS, Gadad AP. Taste Masked Ofloxacin Mouth Disintegrating Tablets Ind Drugs, 2005;42 (1):52-55.
4. Suzuki H, Onishi H, Takahashi Y, Iwata M, Machida Y. Development of oral acetaminophen chewable tablets with inhibited bitter taste. Int J Pharm 2002 27 October;251:123-32.
5. Cerea M, Zheng W, Young CR, McGinity JW.A novel powder coating process for attaining taste masking and moisture protective films applied to tablets Int J Pharm 2004;279:127–39.
6. Robson H, Craig DQM, Deutsch D. An investigation into the release of cefuroxime axetil from taste masked stearic acid microspheres. II. The effects of buffer composition on drug release. Int J Pharm 2000;195:137-45.
7. Xu J, Bovet LL, Zhaoa K. Taste masking microspheres for orally disintegrating tablets. Int J Pharm 2008 15 March;359:63-9.
8. Patravale VB, Prabhu NB. Taste masking of quinine sulphate. Ind J Pharm Sci 2005 27 March:233-5.
9. Breitkreutza J, Bornhoft M, Woll F, Kleinebudde P. Pediatric drug formulations of sodium benzoate: I. Coated granules with a hydrophilic binder. Eur J Pharm Biopharm 2003 14th May;56:247-53.
10. James Swarbrick. Encyclopedia of Pharmaceutical Technology. 3rd ed (2). New York London:Informa healthcare;2007.
11. Barra J, Lescure F, Doelker E. Taste masking as a consequence of the organization of powder mixes. Pharm Acta Helv 1999 7th July;74:37-42.
12. Barrier S, Rigby AS, Diego-Taboada A, Thomasson MJ, Mackenzie G, Atkin SL, Sporopollenin exines: A novel natural taste masking material. LWT - Food Sci Techno 2009;43:73-6.
9. / SIGNATURE OF THE CANDIDATE
REG NO.
10. / REMARKS OF THE GUIDE / Assigned work is feasible and recommended.
11. / NAME AND DESIGNATION OF
11.1 GUIDE / Dr. NAMITA NAIKKHANVTE
M.Pharm, PhD
Assistant Professor
Department of Pharmaceutics
V.I.P.S. BANGLORE-560070.
11.2 SIGNATURE
11.3 HEAD
OF THE
DEPARTMENT / Dr. PRAKASH RAO. B
M.Pharm, PhD
Professor
Department of Pharmaceutics
V.I.P.S. BANGLORE-560070.
11.4 SIGNATURE
12. / 12.1 PRINCIPAL / Dr. D.H. Harish Kumar
M.Pharm, PhD
V.I.P.S. BANGLORE-560070.
12.2 SIGNATURE WITH SEAL
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