“DRY SYRUP FORMULATION OF SOME UNPALATABLE ANTIBIOTICS: AN APPROACH TO IMPROVE THE PALATABILITY AND STABILITY”
DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
BY
PATEL ROHITKUMAR JASHVANTBHAI
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85, KARNATAKA.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATEAND ADDRESS (IN BLOCK LETTERS) / PATEL ROHITKUMAR JASHVANTBHAI
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85
KARNATAKA.
2. /
NAME OF THE INSTITUTION
/ NARGUND COLLEGE OF PHARMACY,DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85
KARNATAKA.
3. /
COURSE OF STUDY AND SUBJECT
/ MASTER OF PHARMACY IN PHARMACEUTICS4. / DATE OF ADMISSION OF COURSE / 1st JUNE 2009
5. /
TITLE OF TOPIC
/ “DRY SYRUP FORMULATION OF SOME UNPALATABLE ANTIBIOTICS: AN APPROACH TO IMPROVE THE PALATABILITY AND STABILITY”6.
7.
8. / BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY:
Oral drug delivery system has been known for decades which are the most widely used route of administration among all the routes, which have been explored till now for the systemic delivery of different dosage forms.
The oral administration of pharmaceutically active substance in the form of tablets or capsules is often problematic in special patient groups such as children and older patients who have difficulties in swallowing the whole solid dosage forms. The suitable dosage forms for these patients may be solutions, suspensions, syrups or emulsions. But most of the drugs do not have acceptable palatability and stability when presented in liquid dosage forms. Hence several techniques are employed to mask the bitterness of the drug and to improve the palatability.
The traditional taste masking techniques such as addition of Sweeteners like sugar, artificial sweeteners, fruit aromas, thickeners and amino acids, often fails to give the pharmaceutical composition an acceptable taste. It is mostly that portion of the active substance in such dosage forms which is dissolved in the saliva and /or in the liquid for administration that generates the unpleasant taste. Also, most of the antibiotics are unstable in water so cannot be formulated as solutions, suspensions, syrups or emulsions so there is a need to develop a taste masked dry syrup to overcome these problems.
Proven method for bitterness reduction has resulted in improved palatability of oral pharmaceutical formulations. Various techniques have been developed to improve taste like polymeric coating technique, complexation with cyclodextrins and ion-exchange resin. All of these methods overcome the bitterness of drug and at the same time retain the stability until in use by altering the solubility of said active substance. In this way only a small portion of said substance or even none of it will dissolve in the suspension or in the mouth.
The present project relates to development of dry syrup for oral administration which consists of coated particles or resin complex comprising of an active substance which has unpleasant bitter taste. These taste-masked coated particles or resin complex of an antibiotic which in the form of dry syrup can maintain its palatability and stability as well over a prolonged period of time. Dry syrups are dissolved or suspended before use in an aqueous liquid such as water, juice or milk as a solvent.
ADVANTAGES OF DRY SYRUP:
Ø Unpleasant and/or bitter taste of a drug can be reduced.
Ø Only a small portion of the active ingredient or even none of it will dissolve in the suspension or in the mouth which will increase the patient compliance.
Ø Storage conditions of these drugs can be improved.
Ø Stability of these drugs can also be increased.
Ø Bioavailability of these drugs can be increased as compared to tablets.
Ø Relatively easily dispensed, easy to carry.
Ø Easy to swallow for paediatric and geriatric patients.
6.2 REVIEW OF LITERATURE :
Literature shows that much work has not been reported on dry syrup. Few reported work of dry syrup are as follows:
1. J. Barra, et al. Demonstrated that chemical or technological operations are used to mask the taste of unpleasant-tasting drugs. To reduce the development cost of such drugs, they proposed a new approach which does not require the modification of the existing formulation nor the use of additional costly technological operations2.
2. Dry syrup preparation of L-carbocysteine in which the sourness inherent to L- carbocysteine can be relieved by a more convenient production process which also involve blending a sugar alcohol and a sweetener having a high sweetness. The preparation can be dispensed relatively easily are easy to carry, can be easily taken, can be taken by suspending or dissolving before using and can be administered to subjects over a wide range from infants to the aged3.
3. WADA, koichi, et al. have formulated epinastine in the form of a powder for treating allergies, dermatitis, rhinitis etc. Epinastine hydrochloride causes two different kinds of tastes with respect to strong bitterness, one is quick acting kind of bitterness and the other is lasting bitterness that is tasted for a quite long time. Strong bitterness can be overcome by the combination of quick and slow acting sweeteners and flavoring agents. For the masking of quick-acting bitterness, saccharin sodium, erithritol and/or aspartame turned out to be effective4.
4. Harmik Sohi, et al, they have demonstrated that the pharmaceutical formulation with a pleasing taste would definitely be preferred over a competitor product and would translate in to batter compliance and therapeutic value for the patient. The desire of improved palatability in this products has prompted the development of numerous formulations with improved performance and acceptability5.
5. Yan Gao, fu-de cui, have demonstrated the effect of different polymers and drug–polymer ratios on the taste masking and the characteristics of the microspheres were investigated. They found that Eudragit S100 was the best for masking the unpleasant taste of roxithromycin among the six kinds of polymers6.
6. Sagarika Bose. Tahara et al, in their review, mentioned that solventless processes can bring significant advantages to the pharmaceutical industry because solventless systems do not require any solvent recovery systems and thus no explosion hazard or solvent exposure to production personnel or no residual solvent in the product. It also reduces time to coat7.
7. Toshitada toyoda, et al, have demonstrated that the dry syrup preparation provides a homogenous dispersion without bitter tastes. Dry syrup preparation can easily taken up by children who dislike a medicine or by elderly person having difficulty swallowing8.
8. Takayuki Yoshida, et al, in their study demonstrated that sodium carbonate and HPMC can be used as the salt and water soluble polymer in the salting out layer, respectively. The drug release rate from the formulation containing the HPMC layer was affected by the sodium carbonate concentration and the media used in the drug dissolution testes. The HPMC layer suppresses the drug release in a medium with the high sodium carbonate concentration, and subsequently increase the drug release rate in a medium with a low sodium carbonate concentration9.
9. Morella AM, et al, have found that when cationic methacrylate polymers having quaternary ammonium functionality such as Eudragit RS100 and Eudragit RL100, were substituted for ethylcellulose as the polymer membrane used in the microencapsulation and formulation of the suspension at the same pH, the resulting suspension remained taste masked for long time10.
6.3 OBJECTIVES OF THE STUDY:
The objectives of the present study is highlighted as given below:
Ø Selection of active substances.
Ø Selection of resins.
Ø Selection of polymers.
Ø Selection of coating methods.
Ø To carry out the preformulation studies.
Ø To carry out compatibility studies.
Ø Optimizing the concentration of resins and polymers.
Ø Optimizing the process parameters.
Ø To develop and formulate the taste masked dry syrup.
Ø To evaluate the formulated dosage forms for in vitro dissolution studies and characterization for physico-chemical stability.
Ø To carry out the stability studies of the formulated dry syrups.
MATERIALS AND METHODS:
Materials
Drugs: Sparfloxacin, Lomefloxacin, Gemifloxacin, Sulfadiazine, etc.
Excipients: Eudragit E-12.5, Eudragit-E-100, Eudragit-EPO, Chitosan, Indian- 204, Indian-234, Amberlight-63, Amberlight-69, Acrylic acid derivatives, etc.
Other reagents: Organic and inorganic solvents etc.
Methods
1. Taste masking with lipophillic polymers.
2. Taste masking by coating with hydrophilic polymers.
3. Taste masking by inclusion complexation.
4. Taste masking by ion-exchange resins.
5. Miscellaneous taste masking techniques:
1. Using effervescent agents,
2. Solid dispersion system,
3. Freeze drying process,
4. Wet spherical agglomeration technique, etc.
7.1. Source of Data
1. Library: Nargund college of pharmacy
2. e-library: Nargund college of pharmacy
3. Digital library, RGUHS (J-Gate@Helinet)
Web sites: www.sciencedirect.com
www.pubmed.com
www.google.com
www.patentstrom.com
www.freepatientonline.com
7.2. Method of Collection of Data
1. Data of physicochemical properties of the drug will be collected through literature search.
2. Experimental studies which includes:
· The formulation evaluation for the compatibility studies.
· Formulation development and evaluation.
· Study of Pre & Post-formulation parameters and in-vitro dissolution studies for the developed formulation.
· Spectrophotometric, HPLC, FTIR methods for the estimation of drug and for analysis of in-vitro dissolution samples.
· Statistical analysis of all the results.
· Solubility studies of drug in various solvents and in buffer system of different pH conditions.
7.3. Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
-NO-
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
- NOT APPLICABLE-
LIST OF REFERENCES:
1. Schwarz FX, Kosilek I. Taste-masking Pharmaceutical Composition. US Patent no.0008765 A1. 2008 January 10.
2. Barra J, Lescure F, Doelker E, Taste masking as a consequences of the organization of powder mixes. Pharmaceutica acta helvetiac1999 July 7; 74; 37-42.
3. Dry syrup preparation. World Intellectual Property Organization (WO/2002/041887). 2002 May 30.
4. Wada, Koichi (JP/JP): (JP) (US only), Nakatani, Manabu (JP/JP) : (JP) (US only), OHKI, Toshimitsu (JP/JP) : (JP) (US only). New dry and Aqueous Epinastine-syrup-formulation. World Intellectual Property Organization (WO/2003037350). 2003 May 8.
5. Harmik Sohi, Yasmin Sultana, Roop K. Khar. Taste masking technologies in oral pharmaceuticals: recent Developments and Approches, [Online]. 2004 [cited 2004 May 25]; Available from: URL:http://dx.dio.org/10.1081/DDC-120037477
6. Yan Gao, Fu-de Cui, Ying Guan, Lei Yang, Yong-sheng Wang, Li-na Zhang. Preparation of roxithromycin-polymeric microspheres by the emulsion solvent diffusion method for taste masking. International journal of pharmaceutics 2006 March 22; 318:62-69.
7. Sagrika bose, Robin H. Bogner. Solventless pharmaceutical Coating Processes: A Review [online]. 2006 [Cited 2006 June 1]; Available from: URL:http://dx.doi.org/10.1080/10837450701212479
8. Toshitada Toyoda, Yoshitsugu Muguruma, Yostika Tomoda. Dry syrup containing Loratadine. US Patent no.0064713 A1. 2008 March 13.
9. Takayuki Yoshida, Hiroaki tasaki, Astushi Maeda, Masataka Katsuma. Mechanism of controlled drug release from a salting-out taste-masking system. Journal of Controlled Release 2008 July 16; 131; 47-53.
10. Morella AM, Pitman IH, Heinicke GW. Taste masked liquid suspension. US patient No.6, 197,348 B1. 2001 march 6.
9. / Signature of the candidate / (PATEL ROHITKUMAR.J.)
10. / Remark of the Guide
11. / Name & Designation of
(in block letters)
Guide
SIGNATURE / Mr. SATEESHA.S.B
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICS
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR,2nd MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85, KARNATAKA.
12. / HEAD OF DEPARTMENT / Dr. CSR LAKSHMI
PROFFESOR AND HEAD
DEPT. OF PHARMACEUTICS
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85, KARNATAKA.
13. / REMARKS OF THE PRINCIPAL
SIGNATURE / PROF. M.S.HARISH
(PRINCIPAL)