<p>FORMULATION, DEVELOPMENT AND EVALUATION OF CEFIXIME ORAL MEDICATED JELLY</p><p>SYNOPSIS FOR M.PHARM DISSERTATION </p><p>SUBMITTED TO RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA.</p><p>BY VISHNU VARDHAN REDDY BEERAM Ι M.PHARM DEPARTMENT OF PHARMACEUTICS, M.E.S COLLEGE OF PHARMACY, ARADESHAHALLY GATE, BANGALORE-562110, KARNATAKA. (2010-2011) ANNEXURE-II </p><p>PROFORMA FOR REGISTRATION OF SUBJECTS FOR P.G. DISSERTATION</p><p>1. NAME OF THE CANDIDATE AND ADDRESS MR.VISHNU VARDHAN REDDY BEERAM (IN BLOCK LETTERS) M.E.S COLLEGE OF PHARMACY, ARADESHAHALLY GATE, BANGALORE-.562110, KARNATAKA.</p><p>2. NAME OF THE INSTITUTION M.E.S COLLEGE OF PHARMACY, ARADESHAHALLY GATE, BANGALORE-.562110, KARNATAKA</p><p>3. COURSE OF STUDY AND SUBJECT MASTER OF PHARMACY IN PHARMACEUTICS </p><p>4. DATE OF THE ADMISSION 30/09/2010</p><p>5. TITLE OF THE TOPIC:</p><p>“FORMULATION,DEVELOPMENT AND EVALUATION OF CEFIXIME ORAL MEDICATED JELLY”</p><p>6. BRIEF RESUME OF THE INTENDED WORK 6.1 NEED FOR THE STUDY Despite tremendous advancement in drug delivery (1), oral route remains the preferred route for the administration of therapeutic agents, low cost of therapy and ease of administration leads to patient compliance. So most of the paediatric formulations also available in different types of oral dosage forms, like syrups, suspensions, reconstituted powders, dispersible tablets, mini tablets etc. But so many problems are arising in usage of that type of formulations in paediatrics, like stability, dosage wastage, dose dumping etc., and also the children’s are not showing the interest to take such type of formulations, and need so much counseling to the mothers to use the above type of formulations in the right directions to their babies. Inconvenience of administration and patient compliance are gaining significant importance in the design of dosage forms. So the present investigation is focused to develop the elegant, acceptable, stable ciprofloxacin oral medicated jelly(2) , using suitable combination of excipients like sodium alginate as a gelling agent and sodium citrate as a source of cation, and to improve its efficacy. Jellies (3, 4) are semisolid to thick viscous fluids that consist of sub microscopic particles in a somewhat rigid or plastic vehicle. They are transparent or translucent, non greasy and mucilage type products. They are generally applied externally for medication, lubrication and some miscellaneous applications. The jelly dosage form can be swallowed easily without water and are soft and smooth. Cefixime (5) is a semi-synthetic (partially man-made), oral antibiotic in the cephalosporin family of antibiotics. The cephalosporin family includes cephalexin (Keflex), cefaclor (Ceclor), cefuroxime (Zinacef), cefpodoxime (Vantin), cefprozil (Cefzil), and many injectable forms. Like other cephalosporins, cefixime stops bacteria from multiplying by preventing bacteria from forming the walls that surround them. </p><p>The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together; bacteria cannot survive without a cell wall. Cefixime is active against a very wide spectrum of bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes (the cause of strep throat), Hemophilus influenzae, Moraxella catarrhalis, E. coli, Klebsiella, Proteus mirabilis, Salmonella, Shigella, and Neisseria gonorrhoeae. The FDA approved cefixime in April 1989.</p><p>Systematic(IUPAC)name; (6R,7R)-7-{[2-(2-amino-1,3-thiazol-4-yl)-2-(carboxymethoxyimino)acetyl]amino}-3-ethenyl-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. </p><p>Pharmacodynamics; Cefixime binds to one or more of the penicillin-binding proteins (PBPs) which inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall, thus inhibiting biosynthesis and arresting cell wall assembly resulting in bacterial cell death. Pharmacokinetics; Absorption; Only 40-50% is absorbed from the GI tract (oral); rate may be decreased if taken with food. Greater absorption from oral suspension than tablets. Distribution; Bile, urine (high concentrations); crosses the placenta. Protein-binding: 65%. Excretion; 20% of an oral dose excreted via urine unchanged; 60% non renal elimination; some is excreted via the faeces from the bile. Substantially removed by dialysis. Dosage; Oral Susceptible infections Adult: 200-400 mg/day as a single dose or in 2 divided doses. Child: 8 mg/kg/day as a single dose or in 2 divided doses; <6 months: Not recommended. Treatment should be continued for 48 hours after disappearance of symptoms.</p><p>Cefixime is an orally administered antibacterial agent in most of the paediatrics. It is having good oral absorptivity and bio availability. But most of the paediatric cefixime formulations are available in syrups, reconstituted powders form, but they are having most of the problems like stability and disliking children’s to take that dosages.</p><p>So the main objective of this present investigation is to develop an elegant, stable and most paediatric acceptable medicated jelly dosage form for oral administration of Cefixime. 6.2 REVIEW OF LITERATURE:</p><p>Studies on other medicated jellies;</p><p> Medicated jelly with Ajowan extract was formulated using polymers like sodium alginate and tragacanth. The jellies were evaluated for their physiochemical parameters like pH, spreadability and stability studies. The antimicrobial activities of the gels were also carried out. Formulations using sodium alginate shows desired properties and significant antimicrobial activity. Ajowan is the dried ripe seed of Trachysperum ammi (L), Sprague, belonging to the family Apiaceae .It has an agreeable taste and an aromatic odour. It is valued for its antiseptic, antispasmodic, stimulant, tonic and carminative properties. It is also effective in treating sore throat, bronchitis, diarrhoea and Cholera .Therefore, the present study was carried out to formulate a medicated jelly with ajowan extract by using different gelling agents like sodium alginate and tragcanth in various proportions. The jellies thus prepared were evaluated for their appearance, pH, spreadability, antimicrobial activity and also for its stability studies.(8)</p><p> Formulation, Development and Evaluation of Ciprofloxacin Hydrochloride Soft Gel for Oral Administration. Inconvenience of administration and patient compliance are gaining significant importance in the design of dosage forms. Difficulty in swallowing (dysphagia) is common among all age groups, especially in elderly and paediatrics. Ciprofloxacin hydrochloride is an orally administered antibacterial agent. The objective of this study was to develop ciprofloxacin hydrochloride soft gel using sodium alginate as a gelling agent and sodium citrate as a source of cat ion. Gels are formed by aggregation of polymers with minimum two components; the gelling agent and the fluid component. Different batches were prepared using three different concentrations of sodium alginate (0.1, 0.4, and 0.8%). The consistency of sodium alginate gel was dependent on the concentration of, sodium alginate, sodium citrate and co-solute. The results of dissolution study of soft gel F3 containing 0.4% sodium alginate and 0.3% sodium citrate revealed that Ciprofloxacin hydrochloride was 85% released in 45 min. and possessed acceptable sensory characteristics when evaluated by human volunteers. Short term stability study carried out for four weeks at different temperatures (0°C and room temperature) showed no considerable changes in performance characteristics of developed optimized formulation.  Pharmacokinetics and Stability of an Enrofloxacin Oral Gel Formulation in Horses. Enrofloxacin, in an oral flavoured gel formation, achieves clinically effective serum concentrations necessary to treat susceptible infections in horses. The formulated gel retains full potency for a 3-mo period. Oral antibiotic choices to treat infections in horses are limited. In many cases, such as peritonitis, osteomyelitis, or pleuropneumonia, to name a few, long-term therapy may be necessary. In instances where owners need to administer the antibiotic doses, the IV or IM route may be difficult or dangerous, and the oral route is preferable. Enrofloxacin is not only another alternative to the few antibiotics currently available to give orally to treat infections in horses, but also offers a broad spectrum of activity. The commercial enrofloxacin tablets, approved for use in dogs, are cumbersome to crush, and the volume of the cattle injection is large, resulting in loss of some of the dose when administered. We developed an oral flavoured gel formulation from the cattle injection that significantly eased administration of the dose. The purpose of this study was to determine whether enrofloxacin achieves clinically sufficient serum concentrations after oral administration of the gel formulation. In addition, the stability of the extemporaneous formulation was studied (9).</p><p>6.3 OBJECTIVES OF THE STUDY: </p><p>The aim of the present work is,</p><p> Formulation of cefixime oral medicated jelly by using suitable optimization technique and to optimize the drug release profile.  Characterization of the prepared oral medicated jelly.  To evaluate the optimized formulations for various in vitro parameters like in vitro dissolution, odour, taste, pH, viscosity studies etc.  Predicting the drug release mechanism.  To subject the optimized formulations for stability studies as per ICH guidelines.  Statistical analysis of all the results.</p><p>7. MATERIALS AND METHOD 7.1 SOURCE OF DATA 1. Library: M.E.S. College of Pharmacy. 2. e-library: M.E.S. College of Pharmacy. 3. The data will be collected from official books such as IP, BP, and USP. 4. Internet source. 5. RGUHS Library, Bangalore (J-Gate) 6. All the National and International journals pertaining to medical and pharmaceutical sciences.</p><p>7. RX list.com 8. Dailymed.com 7.2 MATERIALS: Drug : - Cefixime Gelling agent : - Examples-Sodium alginate, Tragacanth, Pectin (6) etc. Preservatives : - Examples- Methyl and Propyl paraben (7) etc. Cation source :- Sodium citrate Sweetening agent : - Examples- Sucrose, saccharine, Aspartate etc. Solvent :- Distilled water Instruments :- Magnetic stirrer, Dissolution test apparatus, pHmeter, U.V. Spectrophotometer, Brookfield DV-II+Pro viscometer. 7.3 METHODS OF DATA COLLECTION: 1. Literature survey using internet and scientific Journals. 2. Data will be collected from experimental studies which includes:  The compatibility studies of drug and polymers using thermal analysis such as FTIR, and DSC techniques.  Preformulation studies.  Formulation development and evaluation.  Optimization of the oral cefixime medicated jelly using suitable optimization technique.  In vitro drug release studies, physico chemical studies like viscosity, pH, taste studies etc.(10)  Spectrophotometric method for the estimation of drug and for analysis of in-vitro dissolution samples and for the determination of drug loading efficiency.  Predicting the drug release mechanism by curve fit method.  Statistical analysis of all the results.</p><p> Stability studies as per ICH guidelines. 7.4 Does the study require any investigation or intervention to be conducted on patients or other human or animals?</p><p>-NOT APPLICABLE-</p><p>7.5 Has ethical clearance been obtained from your institute?</p><p>-NOT APPLICABLE-</p><p>8.</p><p>REFERENCES:</p><p>1. Bhusan SY, Sambhaji SP, Anant RP, Kakasaheb RM. New drug delivery system for elderly. Indian Drugs 2000;37:312-8. </p><p>2. Ninomiya H, Shimizu T, Dairaku M, Komagata T. Jellied medicinal composition for oral administration, 1999, U.S Patent No,5,932,235.</p><p>3.Yokoyama H, Hirata A, Hamamoto H, Ishibashi M, Yamasaki K, Fujii T. Biguanide drug containing jelly preparation, 2007, U.S Patent app,0053939.</p><p>4. Cooper & Gunn’s dispensing for pharmaceutics, edition 20th, Page no: 214-216, by C.J. carter. </p><p>5. www.wikipedia/encyclopedia.com</p><p>6. Pharmaceutics-II Dispensing and Formulation, page no;287-291, by A.K.Seth.</p><p>7. Rowe R, Sheskey P, Weller P, editors. Handbook of Pharmaceutical Excipients. 4th ed. Chicago: The Pharmaceutical Press; 2003. </p><p>8. Deborah Evangeline.D*, Bhavani Shankar.R 1, Bharath Kumar.A 2,Ramesh Kumar Reddy.Y2. Formulation and Evaluation of Antimicrobial Activity of Medicated Jelly with Ajowan Extract. International Journal of Research in Pharmaceutical and Biomedical Sciences.ISSN: 2229-3701</p><p>9. C. D. Nieuwoudt1, K. L. Epstein2, N. D. Cohen3, D. M. Boothe4 and J. R. Chandler5. Pharmacokinetics and Stability of an Enrofloxacin Oral Gel Formulation in Horses. Internet Publisher: International Veterinary Information Service, Ithaca NY (www.ivis.org), 4-Dec-2004; P1414.1204</p><p>10. Deasy P, Quigley J. Rheological evaluation of deacylated gellan gum (Gelrite) for pharmaceutical use. Int J Pharm. 1991;73:117–23. 9. SIGNATURE OF THE CANDIDATE </p><p>10 REMARKS OF THE GUIDE Recommended to carryout the dissertation</p><p>11 NAME AND DESIGNATION OF </p><p>11.1 GUIDE Dr. CHANDRA PRAKASH M.Pharm, PhD PROFESSOR & HEAD, DEPARTMENT OF PHARMACEUTICS, M.E.S COLLEGE OF PHARMACY , ARADESHAHALLYGATE, BANGALORE-562110, KARNATAKA. 11.2 SIGNATURE </p><p>11.3 CO-GUIDE NOT APPLICABLE</p><p>11.4 SIGNATURE </p><p>11.5 HEAD OF THE DEPT. Dr. CHANDRA PRAKASH M.Pharm, PhD PROFESSOR & HEAD, DEPARTMENT OF PHARMACEUTICS, M.E.S COLLEGE OF PHARMACY , ARADESHAHALLYGATE, BANGALORE-562110, KARNATAKA. </p><p>11.6 SIGNATURE </p><p>12 REMARKS OF THE PRINCIPAL</p><p>12.1 SIGNATURE </p>