SUSTAINED OCULAR DELIVERY OF SPARFLOXACIN FROM pH-TRIGGERED IN SITUGELLING SYSTEM.
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BY
J. SOWMYA
B. Pharm
UNDER THE GUIDANCE OF
Dr. MOHAMMED GULZAR AHMED
M. Pharm, PhD,
DEPARTMENT OF PHARMACEUTICS
SRI ADICHUNCHANAGIRI COLLEGE OF PHARMACY
B.G.NAGARA
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERATION
1 / NAME OF THE CANDIDATE & ADDRESS / J. SOWMYA ,SRI ADICHUNCHANAGIRI COLLEGE OF PHARMACY,
B. G. NAGARA-571448,
NAGAMANGLA(TALUK),
MANDYA (DIST),
KARNATAKA.
PERMANENT ADDRESS:
D/O J. AVANENDHAR REDDY,
H.NO:6-87, BANK COLONY,
SANGAREDDY,
MEDAK (DIST),
ANDHRA PRADESH – 502295.
2 / NAME OF THE INSTITUTE / SRI ADICHUNCHANAGIRI COLLEGE OF PHARMACY,
B.G. NAGARA,
NAGAMANGALA TALUK,
MANDYA DISTRICT,
KARNATAKA -571448.
3 / COURSE OF THE STUDY / MASTER OF PHARMACY (PHARMACEUTICS)
4 / DATE OF ADMISSION / 20-07-2011.
5 / TITLE OF THE TOPIC / SUSTAINED OCULAR DELIVERY OF SPARFLOXACIN FROM pH-TRIGGERED IN SITU GELLING SYSTEM.
06
7 / 6.
BRIEF RESUME OF INTENDED WORK
6.1 Need for study:
Eye diseases are commonly encountered in day to day life, which are cured or prevented through the conventionally used dosage forms like eye drops, ointments etc., Delivery to the internal parts of the eye still remains troublesome due to anatomical and protective structure of the eye1.
Poor ocular bio-availability of drug which is less than 1% from conventional eye drops is due to the physiological barriers of the eye2. Most of the topically applied drugs in the form of eye drops are washed off from the eye by various mechanisms include lacrimation, tear dilution and decrease in residence time3. The primary advantage of ophthalmic ointments over ophthalmic solutions is its increased ophthalmic contact time of drug. Ointmentsalso has disadvantages such as Sticking of eyelids, Blurred vision, Poor patient compliance, Drug choice limited bypartition coefficient4.
Ocular efficiency is closely related to ocular drug bioavailability which may be enhanced by increasing corneal drug penetration and prolonging pre-corneal drug residence time.A significant increase in the pre-corneal residence time of drug and consequently better bio-availability can be achieved by using delivery systems based on the concepts of in-situ gel formation5.
Ocular in-situ drug delivery systems consists of polymer that exhibit sol-to-gel phase transitions due to change in specific physicochemical parameters (pH) and results in ease of application, reduction in frequency of administration, improved patient compliance and comfort6.
Sparfloxacin is a synthetic broad spectrum flouroquinolone group of antibacterial agent, can be administered orally and showed in-vitro anti-bacterial activity against wide range of gram-positive and gram-negative micro-organisms. The minimum inhibitory concentration for sparfloxacin is found to be less than 0.25-10µg/ml7. Sparfloxacin is effective against gram-positive microorganisms such as staphylococci, streptococci, enterococci and gram-negative organisms such as Enterobacteriaceae, Pseudomonas spp., Haemophilus influenzae, and various species8.
The antibacterial activity of sparfloxacin results from the inhibition of DNA gyrase and topoisomerase IV, which is required by bacteria for DNA replication, transcription repair and recombination7.
6.2 REVIEW OF THE LITERATURE:
- Abdul Hasan Sathali A et al.,3has formulated and evaluated of pH-triggered in situGelling Systemof Levofloxacin and concluded that this formulation is an alternate to conventional eye drops toimprove the bioavailability through its longer precornealresidence time and ability to sustain drug release. The patientcompliance may be improved due to the decrease infrequency of drug administration.
- Amin P.D et al.,9 has developed Sustained ophthalmic delivery of ofloxacin from a pH triggeredin situ gelling system and concluded that thedeveloped formulation is a viable alternative toconventional eye drops by virtue of its ability to enhance bioavailability through its longerprecornealresidence time and ability to sustain drug release. Also important is the ease of administration affordedand decreasedfrequency of administration resultingin better patient acceptance.
- Milan C Satia et al.,10has evaluated the ocular pharmacokinetics of sparfloxacin (0.3% w/v) in the aqueous humour of rabbits and concluded thatthe sparfloxacin levels in aqueous humour of rabbits are sufficiently high up to the 6 hours after instillation in the conjunctival sac to provide bactericidal effect against most of the ocular pathogens. Both Cmax: MIC and AUC: MIC ratios are high enough to provide bactericidal effect against most of the ocular pathogens. Sparfloxacin (0.3%) ophthalmic preparation has excellent penetration through cornea.
- Yasmin sultana et al.,11has developed an ophthalmic delivery system of a flouroquinolone antibiotic, based on the concept of ion-activated in situ gelation and concluded that the developed formulation was effective against selected micro-organisms in antimicrobial efficacy studies. The formulation demonstrated better therapeutic efficacy compared with standard eye drops because it improved the clinical parameters monitored for prolonged periods. The developed formulations can be considered as a viable alternative to conventional eye drops.
- Barrett MS et al.,12 has evaluatedsparfloxacin, a novel pyridine carboxylic acid flouroquinolone derivative andwas compared to six other compounds for antimicrobial activity against erythromycin-resistant pneumococci (50 strains).They concluded that sparfloxacin was four-fold more active than ciprofloxacin and ofloxacin. Sparfloxacin appears to possess excellent in vitro activity against erythromycin-resistant S. pneumonia that were often highly resistant to beta-lactams.
- Balasubramaniam, J., et al.,13has performed in vitroand in vivo evaluations of the gellan gum based ocular delivery system for developing an ophthalmic delivery system based on the concept of ion activated insitugelation. Gellan gum, a novel ophthalmic vehicle, which gels in the presence of mono or divalent cations present in the lacrimal fluid, was used as the gelling agent. They concluded that the developed formulations were therapeutically efficacious and provided sustained release of the drug over an 8‐hour period in vitro.
- Nirmal H.B14has developed new trends in controlled and sustained drug delivery system and concluded that the primary requirement of a successfulcontrolled release product focuses on increasingpatient compliance which the in situ gels offer. Sustainedand prolonged release of the drug, good stability and biocompatibility characteristics make the in situ geldosage forms very reliable.
- Nanjwade et al.,15has evaluated sustained ophthalmic in situ gel of ketorolac tromethamine and concluded that 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 sustain drug release. Also importantly is the ease of installation afforded and decreased frequency of instillation resulting in better patient acceptance.
- To develop in situ gel for the ocular local drug delivery.
- To evaluate the in situ gel as a vehicle in local drug delivery system.
- To evaluate the developed gel for various characterizations.
- To evaluate antibacterial activity of sparfloxacin in situ gel.
- To evaluate the effectiveness by means of animal studies.
7.1 MATERIALS:
Drug: sparfloxacin
Polymer: Gellangum, poly acrylic acid (carbopol 940) and hydroxyl propyl methyl cellulose (HPMC).
All other materials used were analytical grade.
7.2 METHOD:
Preparation of solution
Step.1:- Different concentrations of polymers were dissolved in phosphate buffer and allowed to hydrate then surfactant was added.
Step.2:- sparfloxacin was dissolved in suitable alkaline solution separately and adjust the pH.
Step.3:- The drug solution was then added to the polymeric solution under constant stirring until a uniform solution was obtained. Final volume was made up with distilled water.
7.3 SOURCE OF DATA:
- The literature survey will be done by referring the abstracts of all the National and International journals of pharmaceutical sciences.
- The day to day development in this area will be updated by literaturesurveythrough E-publishing and current periodicals in library of SAC College of Pharmacy, B G Nagara.
- Preformulation studies such as:-
- Solubility.
- Compatibility drugs with excipients.
- Calibration (melting point, pH etc.).
- Laboratory investigations such as
7.5Does the study require any investigation or interventions to be conducted on animals/ patients?
yes
7.6Has ethical clearance been obtained from your institution in case of
above?
Will be obtained
7.7 Duration of the study:
The study will be conducted over a period of 9 months.
7.8 Place of study:
,Department of pharmaceutics, Sri Adichunchanagiri College of pharmacy,
B.G.Nagara.
8 / LIST OF REFERENCES:
- Patel V, Agarwal YK. Current status and advanced approaches in ocular drug delivery system. Journal of Global Trends in Pharmaceutical Sciences2011;2(2):131-48.
- Himeshu G, Aqil MD. Sparfloxacin loaded PLGA nanoparticles for sustained ocular drug delivery.Nanomedicine: nanotechnology, biology and medicine 2010;6(2):324-33.
- Hassan AS, Mohanambal E, Arun K. Formulation and evaluation of ph triggered insitu gelling system of levofloxacin. Indian Journal of Pharmaceutical Education and Research 2011;45(1):58-64.
- Mahesh NM,Ashok AH. In situ gel-forming systems for sustained ocular drug delivery.European Industrial Pharmacy2010;5:17-20.
- Tanvi PP, Moin.KM, Vishnu MP. Sustained ophthalmic delivery of ciprofloxacin hydrochloride from an in situ gelling system. Scholars Research Library 2011;3(3):404-10.
- Bharath S, Sindhu A, Sharon F, Basavaraj BV,Deveswaran R, Madhavan V. Sustained Ophthalmic Delivery Of OfloxacinFrom An Ion-Activated In SituGelling System.Pak. J. Pharm. Sci 2009;22(2):175-79.
- Gulzar MD, Narayana charyulu R, Hareesh NM, Prabhakar P. Polymeric strips containing sparfloxacin for the long term treatment of periodontitis. International Journal of Pharma Research 2008;48-53.
- Georgopoulos G, Feistauer SM, Graninger M, Pfleger S, Georgopoulos M. Antibacterial Activity Of Sparfloxacin Against Experimental Renal Infections In Mice. Antimicrobial Agents and Chemotherapy 1992;36(2):505-07.
- Amin PD, Srividya B, Rita MC. Sustained ophthalmic delivery of Ofloxacin from a pH triggeredin situ gelling system. Journal of Controlled Release 2001;73:205–11.
- Milan CS, Vandana DM, Rajiv IM, KabraPK, Myuri K. Pharmacokinetics of topically applied Sparfloxacin in rabbits. Official Publication of All India Ophthalmological Society2005;53(3):177-81.
- Yasmin S, Aqil M,Asgar Ali. Ion-Activated, Gelrite®-Based in Situ Ophthalmic Gels of Pefloxacin Mesylate: Comparison with Conventional Eye Drops 2006;13(3):215-19.
- Barrett MS, Jones RN. Antimicrobial activity and spectrum of Sparfloxacin tested against erythromycin-resistant Streptococcus pneumonia isolates. Diagn Microbial Infect Dis 1996;24(2):113-16.
- Balasubramaniam J, Pandit JK. Ion-Activated In Situ Gelling Systems for Sustained Ophthalmic Delivery of Ciprofloxacin Hydrochloride 2003;10(3):185-191.
- Nirmal HB, Bakliwal SR, Pawar SP. Insitu gel: new trends in controlled and sustained drug delivery systems. International Journal of Pharm tech research 2010;2(2):1398-1408.
15.Manjappa A.S, Basavaraj K, Nanjwade, Manvi FV, Murthy RSR. Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studies. Drug Development Research 2009;70(6):417-24.
9 / SIGNATURE OF THE CANDIDATE10 / REMARKS OF THE GUIDE / The proposed research work is original and designed on rational basis. It would be a good contribution.
11 / 11.1 NAME AND DESIGNATION OF
GUIDE
Guide ship reference No. of RGUHS
11.2 SIGNATURE / Dr. MOHAMMED GULZAR AHMEDM.Pharm, PhD.
PROFESSOR AND HEAD
Department of Pharmaceutics,
S.A.C .College of pharmacy,
B.G. Nagara-571448.
ACA/CDC/PGT-MPh/SACP/86/2008-09
11.3 CO-GUIDE
11.4 SIGNATURE / NOT APPLICABLE
NOT APPLICABLE
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE / Dr. MOHAMMED GULZAR AHMED
M.Pharm, PhD.
PROFESSOR AND HEAD
Department of Pharmaceutics,
S.A.C. College of pharmacy,
B. G. Nagara-571448,
12 / 12.1 REMARKS OF THE PRINCIPAL
12.2 SIGNATURE / Recommended
1