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 Candidateand Address: / RAICHUR VINAY SUDHINDRA
S/o SUDHINDRA PRAHLAD RAICHUR
A-2,Fortune park
E-8,Gulmohar,near sheel public school
Bhopal
Madhya pradesh 462 039
2. / Name of the Institution: /
Al-Ameen College of Pharmacy,
Hosur Road, Bangalore – 560 027.
3.
4. / Course of Study and Subject:
Date of Admission: / M. Pharm – Pharmaceutics
July 2011
5. / Title of the Topic:
“To Design and Evaluate Orally Disintegrating Tablets of Cefpodoxime proxetil using Ion-Exchange Resins”
6.0 / Brief resume of the intended work:
6.1 – Need for the study:
Urinary tract infections (UTI) are one of the most common bacterial infections seen in children. It has been estimated that UTI are diagnosed in 1% of boys and 3-8% of girls. The reported rate of recurrent UTI is 30% with risk greater in infants < 6 months, UTI has accounted for febrile presentations in 7.5% of 442 infants <8 weeks, 5.3% of 945 infants <1 year, 4.1% of 501 children <2 years and 1.7% of 664 children <5 years..3
Pneumonia is the single largest cause of death in children worldwide. Every year, it kills an estimated 1.6 million children under the age of five years, accounting for 18% of all deaths of children under five years old worldwide.4 The incidence of acute respiratory infections in children aged less than 5 years is estimated to be 0.29 and 0.05 episodes per child-year in developing and industrialized countries, respectively, which translates into 151 million and 5 million new episodes each year, respectively. Most cases occur in India (43 million), China (21 million), Pakistan (10 million).
Cefpodoxime proxetil is a third generation cephalosporin antibiotic given orally which is very slightly soluble in water; freely soluble in dehydrated alcohol. Oral bioavailability is about 50% in fasting subjects and may be increased in presence of food. Peak plasma concentrations of about 1.5,2.5 and 4 micrograms/mL have been achieved 2 to 3 hours after oral doses of 100,200 and 400 mg cefpodoxime respectively. Plasma protein binding is 20 to 30%. t1/2 is about 2 to 3 hours. Cefpodoxime Proxetil has good activity against enterobacteriaceae, Hemophilus spp. and Moraxella spp. and is also active against Gram positive bacteria, especially against strepto cocci. It has been used most widely in the treatment of respiratory and urinary tract infection. It is also used in children for treating pharyngitis or tonsillitis. But the extremely bitter taste of this drug limits its use especially in pediatric and geriatric patients. So taste masking of cefpodoxime is very important to improve its acceptability.6
For delivery of pharmaceutical dosage form, the oral route of administration is the most preferred route due to its manifold advantages including ease of ingestion, non-invasiveness, versatility and most important patient compliance. But, still, many patients find it difficult to swallow tablets and hard gelatin capsules and do not take their medication as prescribed. It is estimated that about 50% of the population is affected by this problem which result in a high incidence of non-compliance and ineffective therapy. The difficulty is not only experienced in particular, by pediatrics and geriatric patients, but this also apply to patients who are ill in bed and who are active working patients, who are busy or travelling, especially those who have no access to water. The elderly people eventually will experience difficulties in taking conventional oral dosage forms (viz. solution, suspension, tablets and capsules) because of hand tremors and dysphagia.. Other groups that may experience problem using conventional oral dosage forms include the mentally ill, the developmentally disable, and patients who are non-cooperative or are nauseated.1
For this reason, tablets, which can rapidly dissolve or disintegrate in the oral cavity without need of water, have attracted a great deal of attention. Indeed, the Mouth or fast dissolving tablet have more advantage over the liquid dosage form.1
The United States Food and Drug Administration Center for Drug Evaluation and Research (CDER) terms the fast dissolving/dispersing oral dosage form as Orally Disintegrating Tablet (ODT) and defines as “a solid dosage form containing medicinal substances, which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue”. The significance of these dosage forms is highlighted by the adoption of the term, “Orodispersible Tablet”. European Pharmacopoeia describes, it is a tablet that can be placed in oral cavity where it disperses rapidly before swallowing.1
The key properties of FDT’s are fast absorption of water in to the core of the tablets and disintegration of associated particles into individual components for faster dissolution and greater stability made these tablets popular as a dosage form.2
Thus the proposed study is aimed at developing taste masked orally disintegrating tablets of cefpodoxime proxetil using ion exchange resins like KYRON which are high molecular weight polymers so do not get absorbed by body tissues and is safe for human consumption.8
6.2 REVIEW OF LITERATURE
· Patel TN et al. (2010) Carried out taste masking of topiramate by newer range of ion-exchange resins. Different types of ion exchange resins like Kyron T-104, Kyron T-114, Kyron T-134, Doshion P 542 were used to form complex with Topiramate. Ion exchange resin to drug ratio, effect of pH, effect of temperature, effect of resin soaking time,effect of stirring time on complex formation were optimized. Drug-resin complex was evaluated for swelling, particle size analysis and drug release from drug-resin complex. Developed taste masked drug candidate in this research work become eligible to formulate mouth disintegrating dosage form.9
· Suthar AM et al. (2011) Developed the formulation and evaluation of taste masked suspension of metronidazole with different resins Kyron T‐114, Kyron T‐134 and Indion 234 in different ratios. Prepared suspensions were tested for drug content, in vitro drug release, taste masking, stability study, and molecular properties. Kyron T‐134 at pH 8 showed potential to prepare palatable formulation with MNZ. Thus to overcome taste problem of traditional paediatric dosage form, IER is dominating method to prepare palatable liquid formulation of MNZ.10
· Metker V et al. (2011) Formulated and evaluated Orodispersible tablets of lornoxicam using KYRON T-314 (Polacrillin Potassium) as a novel superdisintegrant. Mouth dissolving tablets of lornoxicam were prepared by wet granulation technique using KYRON T-314 as superdisintegrant and menthol as subliming agent. The study demonstrated potentials for rapid absorption, improved bioavailability, effective therapy and patient compliance.11
· Kulkarani U et al. (2010) worked on formulation and evaluation of pimozide fast dissolving tablets by solid dispersion technique. (DC Kyron T-114) was used as a sweetening agent and (DC Kyron T-314) was used as a superdisintegrant. Solid dispersions of pimozide were prepared by solvent evaporation method. Formulations were evaluated for pre and post compressional parameters. Drug interaction with polymer was checked by FTIR. Stability studies were carried out as per ICH guidelines. The results revealed that formulation P3 was yielded best in terms of dissolution rate. The stability studies revealed that upon storage tablets do not show any change in disintegration time, thickness and drug content after stability studies.2
· Gandhi BR et al. (2011) investigated the use of KYRON T-314 (Polacrillin Potassium) as a novel superdisintegrant to develop mouth dissolving tablets of aceclofenac. Mouth dissolving tablets of aceclofenac were prepared by wet granulation technique using KYRON T-314 as superdisintegrant and menthol as subliming agent. Five formulations with varying concentrations of menthol, KYRON T-314 and mannitol were formulated. It was concluded that prepared tablets using KYRON T-314 disintegrate within few seconds without need of water; thereby enhancing the absorption leading to its increased bioavailability.12
· N.Kanakadurga Devi et al. (2010) carried out Studies on taste masking of levocetrizine di hydrochloride using ion – exchange resins. The purpose of this research work to prepare tasteless complexes of levocetrizine di hydrochloride with Kyron, a cationic ion - exchange resin, to evaluate bitterness and in-vitro drug release from the Drug- Resin complex (DRC). Here, DRC was prepared by batch method using Kyron T -104 and Kyron T- 114 and was found that percentage of drug bound to resin was more with Kyron T -114 and selected it for preparing DRC using ratios from 1:1 to 1:3 and it was founded that 1:3 as the optimized one. The optimized complex was characterized by FT- IR Spectroscopy. Finally , in this work the effect of various parameters like, stirring time, soaking time, temperature, PH on drug loading efficiency were studied and optimized. The in-vitro drug release studies were also carried out. Finally ,the bitterness evaluation was performed by involving the volunteers who have rated drug resin complexes as tasteless and agreeable. The batch process of complexing levo cetrizine with Kyron T - 114 produced efficient drug loading. The study also suggests that an ion exchange resin system is a useful alternate for masking taste of drugs like levo cetrizine.13
· Suthar AM et al. (2010) carried out development of Taste Masked Liquid Formulation of Tinidazole Using Ion-exchange resin Complexes Taste masking was done by complexing TNZ with Kyron T-114, Kyron T-134 and Indion 214 in different ratios. Formulation containing resinates were tested for drug content, in vitro drug release, taste masking, stability study, and molecular property. The resinates prepared with drug-Kyron T-134 ratio (1:2) at pH 8, gave maximum drug loading. Suspension containing above resinates showed more than 80% in-vitro drug release within 30 min. Prepared formulation also showed good stability and can retain its palatable taste. Thus, the “patient friendly dosage form” of bitter drugs, especially for pediatric, geriatric, bedridden, and noncooperative patients, can be successfully formulated using this technology.14
· Madgulkar AR et al. (2011) studied the comparision of in-vitro dissolution profiles of cefpodoxime proxetil PEG solid dispersion with cefpodoxime proxetil pure drug each ratio of of cefpodoxime proxetil and PEG 6000 in solid dispersion in terms of easy application and physical cefpodoxime proxetil and PEG 6000.Statistical models were applied to evaluate each ratio of cefpodoxime proxetil and PEG 6000 in solid dispersion and to find out most suitable ratio of cefpodoxime proxetil and PEG 6000.15
· Darji BH et al. (2007) studied the development and validation of a HPTLC method for the estimation of cefpodoxime proxetil in which the stationary phase used was precoated silica gel 60F254. The mobile phase used was a mixture of chloroform: methanol: toluene (4:2:4 v/v/v). The detection of spot was carried out at 289.0 nm. The standard calibration curve was generated using regression analysis. The developed method was validated in terms of linearity, accuracy, specificity, limit of detection, limit of quantification, intra-day and inter-day precision and repeatability of measurement as well as repeatability of sample application. The proposed method can be successfully used to determine the drug content in marketed formulation.16
· Mendelman MP et al. (1992) carried out comparision of Cefpodoxime proxetil with amoxicillin-clavulanate for the treatment of otitis media. In a multicenter, randomized, investigator-blinded trial, patients were randomly selected to receive eithercefpodoxime proxetil or amoxicillin-clavulanate potassium orally. Findings suggested that clinical efficacy forcefpodoximeadministered twice daily is equivalent to that of amoxicillin-clavulanate administered three times a day.17
6.3 OBJECTIVE OF STUDY
· To formulate and evaluate the taste masked orally disintegrating tablets of Cefpodoxime proxetil by employing ion-exchange resins as taste masking agents.
SPECIFIC OBJECTIVES
1. Preparation of Cefpodoxime proxetil and ion exchange resin complexes.
2. Evaluation of the prepared drug resin complexes (DRC).
3. Formulation of orally disintegrating tablets by direct compression method.
4. Evaluation of the prepared tablets and their comparison with the available marketed product.
5. Stability studies as per ICH guidelines.
7.0 Materials and Methods
7.1 Source of Data:
I. Review of Literature from
a. Journals - such as
· Science Direct.
· Scopus.
· J-Gate@HELINET
· PubMed.
· International Journal of Pharmaceutical Sciences and Nanotechnology.
· International Journal of Drug Development & Research.
· International journal of pharmaceutics.
· European Journal of Pharmaceutics and Biopharmaceutics.
· International Journal of Pharmacy and Pharmaceutical Sciences.
· International Journal of Pharmaceutical Sciences.
b. Internet Browsing.
www.google.com
7.2 - Method of collection of data:
q From Literature
q Laboratory based studies including:
1. Preformulation studies
a) Standardization of method of estimation of Cefpodoxime proxetil.
b) Determination of solubility profile, partition coefficient, IR of pure drug.
c) Evaluation of drug excipient interaction.
2. Preparation of Cefpodoxime proxetil ion exchange resin complex (DRC).
3. Optimization of prepared complex by studying
a) Effect of Drug-Resin ratio on complex formation.
b) Effect of pH on complex formation.
c) Effect of stirring time on drug loading.
d) Effect of soaking time of resin on drug loading.
4. Evaluation of DRC by taste, Particle size analysis and Drug release from DRC.
5. Formulation of orally disintegrating disintegrating tablets using the prepared DRC by direct compression.
6. Evaluation of the prepared orally disintegrating tablets, comparison with the available marketed product.
7. Stability studies as per ICH guidelines.
7.3 - Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, Please describe briefly.
No
7.4 – Has ethical clearance been obtained from your Institution in case of 7.3?
Not applicable
Bibliography
1. Agrawal R, Gupta V. Fast Dissolving Tablets: An Innovative Drug Delivery Technology. Int J Pharm F Res. 2011 Jul; 1(2): 99-118.
2. Kulkarni U, Durgad S.A., Patil B.S, Korwar P.G, Tate S.S. Formulation and evaluation of pimozide fast dissolving tablets by solid dispersion technique. Int J Ph Sci. 2010 Sep; 2(3):724-27.
3. URL: http://www.emro.who.int/publications/emhj/1601/article8.htm (Cited on 25th Nov, 2011).
4. URL: http://www.who.int/mediacentre/factsheets/fs331/en/ (Cited on 24th Nov, 2011).
5. URL: http://www.who.int/vaccine_research/diseases/ari/en/ (Cited on 25th Nov, 2011).
6. United states pharmacopoeia 32,NF 27. 2009;2:1853-54.
7. Karthikeyan D, Karthikeyan M , Ramasamy C. Development of floating microspheres to improve oral bioavalibity of cefpodoxime proxetil. Acta Pharmaceutica Sciencia.2010 May;52:101-04.
8. URL: http://www.corelpharmachem.com (cited on 21st Nov,2011)
9. Patel TN, Patel RP, Patel BV. Taste Masking of Topiramate by Newer Range of Ion-Exchange Resin. Int J Pharm Nano. 2010 Oct;3(3):1105-10.
10. Suthar AM ,Patel MM. Formulation and evaluation of taste masked suspension of metronidazole. Int J App Pharm. 2011 Nov;3(1):16-19.
11. Metker V, Kumar A, Pathak N, Padhee K, Sahoo S. Formulation And Evaluation Of Orodispersible Tablets Of Lornoxicam. Int J Drug Dev & Res 2011 Jan; 3(1): 281-85.
12. Gandhi BR, Mundada AS, Gandhi KR.Evaluation of KYRON T-314 (Polacrillin Potassium) as a novel super disintegrant Drug Dev Int J 3 (2011) :109-14.
13. Kanakadurga Devi N, Prameela Rani A, Madhavi BR. Studies on taste masking of levocetrizine di hydrochloride using ion–exchange resins. Res J Pharm Bio Chem Sci. 2010;1(2):245-53.
14. Suthar AM, Patel MM. Development of Taste Masked Liquid Formulation of Tinidazole Using Ion-exchange resin Complexes .J Pharm Sci Technol. 2010;2(9):303-07
15. Madgulkar AR, Nimbalkar UA, Dhoka MV, Mirajkar RN, Sonawane PN. Comparision of in-vitro dissolution profiles of Cefpodoxime proxetil PEG solid dispersions with Cefpodoxime proxetil Int J Res A Pharm 2011 Mar;2(2):650-54
16. Darji BH, Shah NJ, Patel AT, Patel NM Development and validation of a HPTLC method for the estimation of cefpodoxime proxetil. Indian J Pharm Sci. 2007;69: 331-3.
17. Mendelman PM, Del Beccaro MA, McLinn SE, Wesley MT. J pedi 1992;121(3):459-65.
9.0 / Signature of the Candidate: / ( RAICHUR VINAY SUDHINDRA)
10.0 / Remarks of the Guide: /
Recommended
11.0 / Name and Designation of:
11.1 Institutional Guide: /
Mrs. AISHA KHANUM
Assistant ProfessorDepartment of pharmaceutics.
Al-Ameen College of Pharmacy
Bangalore- 560 027
11.2 Signature:
11.3 Institutional Co - Guide: / Mr. VINAY PANDIT
Lecturer
Department of pharmaceutics.
Al-Ameen College of Pharmacy
Bangalore- 560 027
11.4 Signature:
11.5 Head of the Department: / Dr. (Mrs.) V. KUSUM DEVI
Professor and Head
Department of Pharmaceutics
Al-Ameen College of Pharmacy
Bangalore- 560 027
11.6 Signature:
12.0 / 12.1 Remarks of the Chairman and Principal / Forwarded to the University for scrutiny
12.2 Principal / Prof. B. G. SHIVANANDA
Principal
Al-Ameen College of Pharmacy,
Hosur Road, Bangalore – 560 027
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