RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
[pic]
M. PHARM SYNOPSIS
YEAR OF ADMISSION - 07/09/2012
TITLE OF THE SYNOPSIS
“FORMULATION AND EVALUATION OF
IN SITU OCULAR GEL OF LEVOFLOXACIN”
BY
Mr. SHASHI RANJAN
M. PHARM, PART- I
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDANCE OF
Professor and Head
DEPARTMENT OF PHARMACEUTICS
INSTITUTION
GAUTHAM COLLEGE OF PHARMACY
R. T. NAGAR, BANGALORE-32,
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
| | | |
|1. |NAME OF THE CANDIDATE AND ADDRESS |SHASHI RANJAN |
| | |DEPARTMENT OF PHARMACEUTICS |
| | |GAUTHAM COLLEGE OF PHARMACY |
| | |SULTHAN PALAYA, R.T NAGAR (PO) |
| | |BENGALURU – 32, KARNATAKA. |
| | | |
|2. |NAME OF THE INSTITUTION |GAUTHAM COLLEGE OF PHARMACY, |
| | |SULTHAN PALAYA, R.T NAGAR (PO) |
| | |BENGALURU – 32, KARNATAKA. |
| | | |
|3. |COURSE OF STUDY AND SUBJECT |MASTER OF PHARMACY IN |
| | |PHARMACEUTICS |
| | | |
|4. |DATE OF ADMISSION TO COURSE |07/09/2012 |
| | | |
|5. |TITLE OF THE TOPIC |FORMULATION AND EVALUATION OF |
| | |IN SITU OCULAR GEL OF LEVOFLOXACIN |
|6. |BRIEF RESUME OF THE INTENDED WORK |
| |6.1 NEED FOR THE STUDY |
| | |
| |Eye is the unique and vital organ of body. It is considered as window of the soul. There are many eye ailments which can affect this |
| |organ and one can even loss the eye sight. Therefore many ophthalmic drug delivery systems are available which are classified as |
| |conventional and novel drug delivery systems1. An ideal ophthalmic formulation should be administrated in eye drop form, without causing|
| |blurred vision or irritation2. |
| |Although various formulation exists in market for ocular drug delivery but are not able to provide highest bioavailability related to |
| |administered dose. Whenever an ophthalmic drug is applied through a conventional dosage form to the anterior segment of the eye, only |
| |small amount (5%) actually penetrates the cornea and reaches the interior tissue of the eyes. Factors that affects drug bioavailability |
| |includes rapid solution drainage by gravity, induced lachrymation, blinking reflex, normal tear turnover, superficial absorption of drug|
| |into the conjunctiva and sclera, rapid removal by the peripheral blood flow and low corneal permeability (act as lipid barrier). The |
| |progress has been made in gel technology for the development of droppable gel. They are liquid upon instillation and undergo phase |
| |transition in the ocular cul-de-sac to form visco-elastic gel and this provides a response to environmental changes3. |
| |In situ gel-forming drug delivery systems prepared from polymers that exhibit sol-to-gel phase transitions due to a change in a specific|
| |physicochemical parameter in the cul-de-sac. Deacetylated gellan gum (an exocellular polysaccharide of microbial origin, commercially |
| |available as Gelrite®) is an interesting in situ gelling polymer that has been tested since it seems to perform very well in humans. |
| |Preparations of Gelrite are dropped into eyes; gel formation takes place, induced by the electrolytes of the tear fluid. The other in |
| |situ gelling compound examined, sodium alginate, is widely used in pharmaceutical preparation. Similarly, aqueous solutions of alginate |
| |(a natural polysaccharide extracted from brown sea algae) also form gels when instilled into the eye4. |
| | |
| |Ideally, an in situ gelling system should be a low viscous, free flowing liquid to allow for reproducible administration to |
| |the eye as drops, and the gel formed following phase transition should be strong enough to withstand the shear forces in the cul-de-sac |
| |and demonstrated long residence times in the eye. In order to increase the effectiveness of the drug, a dosage form should be chosen |
| |which increases the contact time of the drug in the eye. This may then prolong the residence time of the gel formed in situ along with |
| |its ability to release drugs in sustained manner will assist in enhancing the bioavailability, reduce systemic absorption and reduce the|
| |need of frequent administration leading to improved patient compliance5. |
| |Levofloxacin is a broad spectrum antibiotic of the Fluoroquinolone drug class. Its spectrum of activity includes most strains of |
| |bacterial pathogens responsible for respiratory, urinary tract, gastrointestinal, and abdominal infections, including Gram negative |
| |bacteria, Gram positive bacteria and atypical bacterial pathogens. It is used for the treatment of bacterial conjunctivitis caused by |
| |organisms like Corynebacterium species, Staphylococus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus and |
| |Serratia marcescens. Levofloxacin inhibits bacterial type II topoisomerases, topoisomerase IV and DNA gyrase. Levofloxacin, like other |
| |fluoroquinolones, inhibits the subunits of DNA gyrase, two subunits encoded by the gyrA gene. This results in strand breakage on a |
| |bacterial chromosome, supercoiling, and resealing; DNA replication and transcription are inhibited. Levofloxacin and other |
| |fluoroquinolones are valued for this broad spectrum of activity, excellent tissue penetration, and for their availability in both oral |
| |and intravenous formulations. The plasma half-life of the drug has been estimated to range from 6 to 8 hours. It is subjected to renal |
| |metabolism6. Levofloxacin is a zwitterion at physiological pH, possessing a carboxylic group with pKa = 5.5, a piperazinyl group with pKa|
| |= 8.0 and another proton accepting function with pKa = 6.8 ± 0.37. |
| |Levofloxacin is available in tablet form, injection, oral solution, as well as used in prescription eye and ear drops. The aim of the |
| |present study is to prepare in situ ophthalmic gel of Levofloxacin to enhance ocular bioavailability and reduce dose frequency and |
| |thereby increasing patient compliance. |
| |6.2 REVIEW OF LITERATURE |
| |Srividya et al (2001)., describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, ofloxacin, |
| |based on the concept of pH triggered in situ gelation. Polyacrylic acid (Carbopol 940) was used as the gelling agent in combination with|
| |hydroxypropylmethyl cellulose (Methocel E50LV) which acted as a viscosity enhancing agent. The developed formulation was therapeutically|
| |efficacious, stable, non-irritant and provided sustained release of the drug over an 8 h period. The developed system is thus a viable |
| |alternative to conventional eye drops8. |
| |Harish et al (2009)., developed in situ oral topical gels of clotrimazole based on the concept of pH triggered and ion activated |
| |systems. The system utilizes polymers that exhibit sol-to-gel phase transition due to change in specific physico-chemical parameters. A |
| |pH triggered system consisting of carbopol 934P (0.2-1.4% w/v) and ion triggered system using gellan gum (0.1-0.75% w/v) along with |
| |hydroxyl propyl methyl cellulose E50LV was used to prolong the release of clotrimazole (0.1% w/v). Formulations were evaluated for |
| |gelling capacity, viscosity, gel strength, bioadhesive force, spreadability, microbiological studies and in vitro release. The use of |
| |carbopol as in situ gel forming system was substantiated by the property to transform into stiff gels when the pH was raised, whereas in|
| |gellan gum this transformation occurred in the presence of monovalent/divalent cations. Effect of calcium carbonate and other process |
| |parameters optimized and found that increase in calcium ions produced stronger gels. The drug content, clarity and pH of the formulation|
| |were found to be satisfactory. The viscosity was found to be in the range 5 to 85 centipoise for the sol, whereas for the gels it was up|
| |to 16000 centipoise. The formulation showed pseudoplastic flow with thixotrophy. The maximum gel strength (using texture analyzer) and |
| |bioadhesion was found to be up to 6.5 g and 4 g respectively. The optimized formulations were able to release the drug up to 6 h. The |
| |formulation containing gellan gum showed better sustained release compared to carbopol based gels9. |
| |Kamel et al (2002)., developed Pluronic F-127 based formulations of timolol maleate to enhance its ocular bioavailability. The effect of|
| |isotonic agents and PF-127 on concentrations on the rheological properties of the prepared formulations was examined. Different |
| |formulations containing combinations of PF -127 with HPMC/CMC/MC in various concentrations were also prepared and the effects of these |
| |agents on the viscosity and drug release characteristics of PF-127gels were studied. In vivo studies on albino rats showed highest % |
| |(15%) with PF-127 in combination with 3% MC when compared with 0.5% timolol maleate aqueous solution10. |
| |Yadav et al (2008)., evaluated and compared the efficacies of eye drops and in situ forming gel of pefloxacin mesylate in pseudomonas |
| |induced conjunctivitis in 40 rabbits. The in situ forming gel of pefloxacin mesylate was formulated as a liquid and when administered in|
| |the cul-de-sac, it gets converted to gel. The objective of the present research work was to demonstrate the in vivo activity of in situ |
| |gelling formulation and compared with marketed eye drops. No difference was obtained in all parameters of conjunctivitis on day 0, |
| |between in situ gelling formulation and marketed eye drops, indicating that severity of conjunctivitis was similar initially between the|
| |two groups. Comparison of scores obtained with marketed eye drops and in situ gel formulation indicated that In situ gelling formulation|
| |was faster in relieving symptoms of conjunctivitis. The findings of the present study indicate that in situ forming gel of pefloxacin |
| |mesylate is a potential delivery system for the treatment of pseudomonas induced conjunctivitis11. |
| |Shivsharan et al (2011)., developed three simple, precise and economical UV methods for the estimation of norfloxacin in pharmaceutical |
| |dosage form. Method A is absorbance maxima method, norfloxacin has the absorbance maxima at 277 nm. Method B is the first order |
| |derivative spectra, the absorbance was measured at λmax =287 nm and λmin =264 nm and the difference was measured for the respective |
| |concentration of standard and was plotted against concentration and regression equation was calculated. Method C applied was area under |
| |curve (AUC), in the wavelength range of 262-289 nm. Linearity for detector response was observed in the concentration range of 1-6μg/mL |
| |for all three methods. The proposed methods were successfully applied for the determination of norfloxacin in commercial pharmaceutical |
| |preparation12. |
| |Hongyi et al (2007)., developed a thermo-sensitive in situ gelling and mucoadhesive ophthalmic drug delivery containing puerarin based |
| |on poloxamer analogs (21% (w/v), poloxamer407/5% (w/v), poloxamer188 and carbopol (0.1% (w/v) or 0.2% (w/v), carbopol 1342P NF). The|
| |combined solutions would convert to firm gels under physiological condition and attach to the ocular mucosal surface for a |
| |relative long time. The incorporation of carbopol 1342P NF not only affected the pseudoplastic behavior with hysteresis of the|
| |poloxamer analogs solution and lead to higher shear stress at each shear rate, but also enhanced the muco-adhesive |
| |force significantly. In vitro release studies demonstrated diffusion-controlled release of puerarin from the combined |
| |solutions over a period of 8 hour. In vivo evaluation indicated the combined solutions had better ability to |
| |retain drug than poloxamer analogs or carbopol alone. It appeared that ocular bioavailability can be increased more |
| |readily by using in situ gelling and mucoadhesive vehicle13. |
| |J. Varshosaz et al (2008)., formulated thermosensitive chitosan/poloxamer in situ gel for ocular delivery of ciprofloxacin. Aqueous |
| |solutions of drug in chitosan/ Pluronic (poloxamer) were prepared to identify suitable compositions with regard to gel forming |
| |properties and drug release behavior. Mixtures of solutions of Pluronic (10-25% w/w) with chitosan (0.1-0.3% w/w) of different molecular|
| |weights (Mw) were prepared. The formulation consisted of 15% Pluronic and 0.1% low Mw chitosan, with the highest release efficiency |
| |(46.61 ± 0.41%) and an acceptable mean release time (1.94 ±0.27hr), is suggested as asuitable ophthalmic preparation for sustained |
| |release of ciprofloxacin14. |
| |Basavaraj K Nanjwade et al (2009)., formulated and evaluated an opthalmic delivery system for non steroidal anti-inflammatory drug, |
| |ketorolac tromethamine, based on the pH triggered in situ gelation. Polyacrylic acid was used as a gelling agent along with |
| |hydroxypropylmethylcellulose (Methocel K4M) which acted as a viscosity enhancing agent. Compatibility studies of the drug and excipients|
| |were carried out using differential scanning calorimetry (DSC). The developed formulation was therapeutically efficacious, stable, |
| |non-irritant, and provided sustained drug release over an 8h. The developed formulation is a viable alternative to conventional eye |
| |drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to produce sustained |
| |drug release15. |
| | |
| |6.3 OBJECTIVES OF THE STUDY |
| |The main objective of the present study is to formulate and evaluate Levofloxacin in situ ocular gel to |
| |Improve the local bioavailability |
| |Reduce dose concentration |
| |Improve patient acceptability |
| |Increase contact time |
| |Increase precorneal residence time |
| |Decrease nasolacrimal drainage of the drug |
| |Prolong the effect of the drug hence frequent instillation of the drug is not required. |
|7. |MATERIALS AND METHODS |
| | Drug : Levofloxacin |
| |Polymer : HPMC, HEC, HPC, Carbomer, Carbopol-934P, Chitosan, Methylcellulose, Tween 90, EDTA, PVA or any other |
| |suitable polymers. |
| |Excipients : HPMC, HEC, HPC, Carbomer, Carbopol-934P, Chitosan, Methylcellulose, Tween 90, EDTA, PVA or any other |
| |suitable polymers. |
| |Method : Ocular in situ gelling system of Levofloxacin drug can be prepared by any one of the method |
| |pH induced in situ gelation |
| |Ion activated in situ gelation |
| |Thermo- sensitive in situ gelation |
| | |
| |7.1 EVALUATIONS |
| |Pre formulation studies includes |
| |Complete characterization of drug and polymers and its analytical method development |
| |Drug excipient compatibility studies can be confirmed by carrying out FTIR spectral studies16 |
| |Melting point |
| |Formulation studies includes |
| |Determination of pH17 |
| |Clarity 17 |
| |Gelation studies18 |
| |Rheology19 |
| |a. Viscosity |
| |b. Spreadability |
| |Phase transition temperature20 |
| |Isotonicity studies19 |
| |Sterility studies19 |
| |Drug content uniformity17 |
| |In vitro drug release study in simulated tear fluid18 |
| |Ocular irritancy test19 |
| |Accelerated stability studies21 |
| | 7.2 METHOD OF COLLECTION OF DATA |
| | |
| |Literature review including pub med/med line and internet search |
| |Lab experiment |
| |Does the study require any investigations or invention to be conducted on patients or other human or animals? If so, please mention |
| |briefly. |
| |Yes |
| |7.4 Has ethical clearance been obtained from your institution in case of |
| |7.3? |
| |Yes |
|8. |REFERENCES |
| |Mohan EC, Jagan MK, Venkatesham A. Preparation and evaluation of in situ gels for ocular drug delivery, J. Pharm. Res, 2009, |
| |2(6),1089-1094. |
| |Ganguly S, Dash AK. A novel in situ gel for sustained drug delivery and targeting. Int. J. Pharm, 2004, 276, pp. 83–92. |
| |Swati G, Suresh PV. Carbopol/chitosan based pH triggered in situ gelling system for ocular delivery of Timolol Maleate, Pharm. Sci. |
| |2010, 78, pp. 959-976. |
| |Balasubramaniam J, Kant S, Pandit JK. In vitro and in vivo evaluation of the Gelrite gellan gum-based ocular delivery system for |
| |indomethacin, Acta Pharm, 2003, 53(4), pp. 251-61. |
| |Indu PK, Manjit S, Meenakshi K. Formulation and evaluation of ophthalmic preparations of Acetazolamide, Int. J. Pharm, 2000, 199, pp. |
| |119–127. |
| | Laurence B, John L, Keith P. Goodman & Gilman's The Pharmacological Basis of Therapeutics. McGraw-Hill Prof |
| |Med/Tech. ISBN 978-0-07-142280-2. Retrieved 30 October 2012. |
| |Michot JM, Seral C, Van Bambeke F, Mingeot-Leclercq MP, Tulkens PM. Influence of efflux transporters on the accumulation and efflux of four|
| |quinolones (ciprofloxacin, levofloxacin, garenoxacin, and moxifloxacin) in J774 macrophages. Antimicrob. Agents Chemother, 2005, 49(6), pp.|
| |2429-2437. |
| |Srividya B, Cardoza RM, Amin PD. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system, J. Control. Rel,|
| |2001, 73(2‐3), pp. 205‐211. |
| |Harish NM, Prabhu P, Charayu RN, Subrahmanyam. Formulation and evaluation of in situ gel containing clotrimazole for oral candidiasis, |
| |Indian J. Pharm. Sci, 2009, 71(4), pp. 421‐427. |
| |Kamel LAH. In vitro and in vivo evaluation of pluronic F 127-based ocular delivery system for timolol maleate, Int. J. Pharm, 2002, 241,|
| |pp. 47-56. |
| |Yadav S, Parvez N. A comparative evaluation of 0.3% eye drops and in situ forming gel of pefloxacin mesylate in experimentally induced |
| |Pseudomonas conjunctivitis. Continental J. Pharmacol. Toxicol. Res, 2008, pp. 1-579. |
| |Shivsharan T, Ghante MR, Sawant SD. Three simple spectrometric methods for norfloxacin in bulk and tablet dosage form, Int. J. Pharm. |
| |Tech, 2011, 3(2), 2757-2764. |
| |Hongyi Q, Wenwen C, Chunyan H, Chuming C, Wenmin L, Chunjie W. Development of a poloxomer analogs /carbopol in situ Gelling and |
| |mucoadhesive ophthalmic delivery system for puerarin, Int.J.Pharm, 2007,337, pp. 178-187. |
| |Varshosaz J, Tabbakhian M, Salmani Z. Designing of a thermoreversible chitosan/poloxamer in situ gel for ocular delivery of |
| |ciprofloxacin, The open drug delivery, 2008, 2, pp. 61-70. |
| |Basavaraj K, Nanjwade, MAS, Murthy RSR, Yuvaraj P D. A novel pH-triggered in situ gel for sustained ophthalmic delivery of Ketorolac |
| |tromethamine. Asian J pharm sci, 2009, 4(3), pp. 189-99. |
| |Rahul N, Venkatakrishnakiran P, Dhanalakshmi P, Prasannaraju Y: Formulation and evaluation of in situ gelling systems for ocular |
| |delivery of Doxycycline hyclate. Journal of Innovative Trends in Pharmaceutical Sciences, 2012, 3(1), pp. 1-7. |
| |Shashank N, Bharani S, Thakur RS. Formulation and evaluation of pH triggered in situ ophthalmic gel of moxifloxacin hydrochloride, Int. |
| |J. Pharm. Sci, 2012, 4(2), pp. 452-459. |
| |Jagdish B, Shri k, Jayanta KP. In vitro and in vivo evaluation of the gelrite gellan gum-based ocular delivery system for indomethacin, |
| |Acta Pharm, 2003, 53, pp. 251-261. |
| |Lekhraj V, Mohammad S, Navdeep S, Ritu M, Gilhotra, Siddharth M. Development of phase change solutions for ophthalmic drug delivery |
| |based on ion activated and pH induced polymers, Int. J. Pharm, Professional’s Res, 2010, 1(2), pp. 137-144. |
| |Mansour M, Mansour S, Mortada N. In situ Forming Gels Ocular Poloxamer-based ciprofloxacin hydrochloride in situ forming gels, Ind. |
| |Pharm, 2008, 34, pp. 744-752. |
| |Bhoyar BS, Agnihotri VV, Bodhankar MM. Design of polyethylene polyoxypropylene block Co-Polymer based in situ gelling system for |
| |localized ocular drug delivery, Int. J. Res. Pharm and Chem, 2011, 1(3). |
|9. |Signature of Candidate | |
|10. |Remarks of the guide |
| |The above information is true to the best of my knowledge and the work will be done under my guidance. |
|11. |11.1 Name and Designation of Guide |Dr. PRASANTH V.V, M. Pharm., PhD |
| | |Department of Pharmaceutics |
| | |Gautham College of Pharmacy |
| | |Sulthan palaya, R.T Nagar (P.O) |
| | |Bangalore – 560 032, Karnataka. |
| |11.2 Signature | |
| |11.3 Co-Guide (IF ANY) | |
| |11.4 Signature | |
| |11.5 Head of the Department |Dr. PRASANTH V.V ,M. Pharm., PhD |
| | |Professor & Head |
| | |Department of Pharmaceutics |
| | |Gautham college of Pharmacy |
| | |Sulthan palaya, R.T Nagar (P.O) |
| | |Bangalore – 560 032, Karnataka. |
| |11.6 Signature | |
|12. |12.1 Remarks of the Chairman and Principal |
| |The above mentioned information is correct and I recommend the same for approval. |
| |12.2 Signature |Mrs. ARCHANA SAMY,M. Pharm, (PhD) |
| | |Principal |
| | |Gautham college of pharmacy |
| | |Sulthan playa, R.T Nagar (P.O) |
| | |Bangalore-32, Karnataka. |
................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- archives of biological sciences journal
- definition of social sciences pdf
- blackrock health sciences fact sheet
- list of social sciences degrees
- blackrock health sciences trust
- blackrock health sciences stock
- archives of biological sciences impact
- institute of mathematical sciences chennai
- university of natural health scam
- university of texas health system
- university of tampa health center
- university of medical sciences ondo