M. PHARM DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIVGANDHIUNIVERSITY OF HEALTH
SCIENCES, KARNATAKA. BENGALURU.
.
BY
MD. ASHADUZ ZAMAN
B.Pharm.,
UNDER THE GUIDANCE OF
Mr.SHANKRAYYA. MM.Pharm., (Ph.D).
ASSISTANT. PROFESSOR
P. G. DEPARTMENT OF PHARMACEUTICSS. C. S. COLLEGE OF PHARMACY,
HARAPANAHALLI-583131
2011-2012
Rajiv Gandhi University of Health Sciences,
Karnataka. Bengaluru.
Annexure – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
01 / Name and Address of the Candidate / MD.ASHADUZ ZAMANS/O MD. ABDUL KADIR .
VILL-GERUATI.
P.O-GERUATI BAZAAR.
DIST-NAGAON.
STATE-ASSAM.
PIN-782140
02 / Name of the Institution /
T. M. A. E. SOCIETY’S
S. C. S. COLLEGE OF PHARMACY,HARAPANAHALLI – 583 131
KARNATAKA.
03 / Course of the Study Branch / M.PHARM. (PHARMACEUTICS)
04 / Date of Admission to course / 06/07/2011
05 / Title of the Topic / FORMULATION AND EVALUATION OF SITE SPECIFIC DELIVERY SYSTEM OF GEMIFLOXACIN FOR THE TREATMENT OF PERIODONTAL DISEASES
06 / Brief resume of the intended work
6.1. Need for the Study / Enclosure – I
6.2. Review of the Literature / Enclosure – II
6.3. Objective of the Study / Enclosure – III
07 / Materials and Methods
7.1. Source of data / Enclosure – IV
7.2. Methods of collection of data / Enclosure – V
7.3. Does the study require any
Investigations on animals?
If yes give details / No
7.4. Has ethical clearance been
obtained form your institution
in case of 7.3. / Not applicable
08 / List of References / Enclosure – VI
09 / Signature of the Candidate / (MD.ASHADUZ ZAMAN)
10 / Remarks of the Guide / The work is well designed with best of my knowledge upon extensive literature review. This work will be carried out in the pharmaceutics laboratory by the above said student under my supervision.
11 / Name and Designation of
(In Block Letters)
11.1. Guide
ACA/CDC/PGT-M.Ph/SCS/02/2010-11
11.2.Signature
11.3.Co-Guide (if any)
11.4.Signature
11.5. Head of the Department
11.6.Signature / Mr.SHANKRAYYA.M
M. Pharm., (Ph.D)
ASSISTANT PROFESSOR
P.G.Department ofPharmaceutics
S.C.S. College of pharmacy,
Harapanahalli-583131, Karnataka.
Prof. VENKATESH. J.S.
B.Sc., M.Pharm.,( Ph. D).
Professor and Head
P.G.Department ofPharmaceutics
S.C.S. College of pharmacy,
Harapanahalli-583131, Karnataka.
Prof. VENKATESH. J.S.
B.Sc., M.Pharm.,( Ph. D).
12 / Remarks of the Principal
12.1. Signature / The present study is permitted to perform in the Pharmaceutics laboratory of our institution by above said student.
DR.R.NAGENDRA RAO
ENCLOSURE-I
06. Brief resume of the intended work
6.1 Need for study-
Periodontal disease is one of the world’s most prevalent chronicdiseases, which has been considered as a possible risk factor inother systemic diseases such as cardiovascular disease, includingcoronary heart disease and stroke and pre-term low birthweight infants.1
Periodontitis (pyorrhoea) is a plaque-induced chronic inflammatory condition leading to the loss of tooth-supporting structures, namely periodontal ligament and alveolar bone. The current microbiological treatment of periodontitis is through either the mechanical cleaning of the teeth with systemic antibiotics or a localized delivery system incorporating an antibiotic. The use of systemic antibiotics raises a number of issues, like bacterial resistance to administered antibiotic and unpleasant or toxic side effects. Large doses must be taken in order to achieve sufficient concentrations in the gingival crevicular fluid of the periodontal pockets; this brings with it the associated side effects of antibiotics and problems regarding antibiotic resistance.
Because of these considerations, a variety of specialized local delivery systems (i.e., intrapocket devices) were designed to maintain the antibiotic in the gingival crevicular fluid at a concentration higher than that achieved by systemic administration2.
Gemifloxacin is novel fluoroquinolone derivative.It is active against Gram positive and Gram negative microorganisms. It is freely soluble in water. Its bioavailability is 71% and its half life is 1-2 hrs. It is administered orally3.
In view of all above reasons, an attempt will be made to optimize the therapeutic effect of gemifloxacin in the treatment of periodontitis as dental inserts.
ENCLOSURE-II
6.2 Review of Literature:
Bansal K., Rawat M.K. et al., (MAY 2009)2developed satranidazole-containing mucoadhesive gel for the treatment of periodontitis. Different mucoadhesive gels were prepared, using various gelling agents like sodium carboxymethylcellulose (SCMC), poloxamer407, Hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl celluloseand the mucoadhesive polymer carbopol 934P. The gels were studied for different mechanical properties, such as Mucoadhesivestrength, hardness, compressibility, adhesiveness, and cohesiveness through Texture Profile Analyzer. In vitro satranidazole release from the prepared formulations was also determined and compared with marketed preparation of metronidazole (Metrogyl® gel).
Mohammed Gulzar Ahmed, Charyulu RN et al.,(AUG 2009)4PreparedChitosan films containing tetracycline in three different concentrations were prepared by the solution casting method, using 1% v/v acetic acid solution for therapy of periodontal desease. The prepared films were evaluated for various properties such as weight variation, tensile strength, stability studies, in-vitro release and mass balance studies. The stability studies did not show any significant changes. Static dissolution studies showed a burst release initially followed by a progressive fall in the release of the drug, and also showed extendedrelease when cross-linking was attempted. The in-vitro release kinetics of tetracycline followed the zero order pattern.
Prabhushankar G.L., Gopalkrishna B. et al.,(2010)5 Prepared Levofloxacin films by solvent casting technique using ethyl cellulose and other co‐polymers in chloroform: dichloromethane (1:1) solvent with dibutyl phthalate and PEG 400 as plasticizers. FT‐IR and UV spectroscopic methods revealed no interaction between Levofloxacin and polymers. The films were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, tensile strength, surface pH and invitro antibacterial activity.
Mohammed Gulzar Ahmed, Harish, NM et al., (FEB.2009)6PreparedChitosan films containing ciprofloxacin alone and in combination with diclofenac sodium were prepared by solvent casting method. Some of the drug-loaded films were cross linked with 2% glutaraldehyde for 2 and 4 h, respectively. The films were then evaluated for their physicochemical properties including weight variation, thickness, tensile strength, in vitro release, stability and antibacterial activity. Mean weight and thickness data showed that the different films were uniform. Tensile strength was maximum for drug-free films and minimum for films containing the highest amount of drug(s). In vitro drug release data indicate that the films showed an initial burst release followed by sustained release of the drug(s). Films stored at refrigerated conditions exhibited slower degradation rate. The drug-loaded films that were cross linked for 4 h had inhibitory effect on Staph mutans for up to 24 days.
Mastiholimath V.S., Dandagi P.M. et al.,(FEB.2006)7Prepared dental implant of 0.25sq cm.for site specific one-time continuous delivery of ornidazole an antimicrobial compound with excellent activity against anaerobic micro-organism in the treatement of periodontal disease was prepared by solvent casting technique using ethyl cellulose, hydroxyl propyl cellulose, hydroxypropylmethyl cellulose K4M and eudragit RL-100 With dibutyl phthalate is plasticizer.The physiochemical parameters like thickness, weight variation, content uniformity and release characteristics were evaluated .The drug release was initially high on day one to achieve immediate therapeutic level of drug in pocket, fallowed by marked fall in release by day two and progressive moderate release profile to maintain therapeutic level following anomalous transport mechanism .Formulation V6 released 97.07 % of drug at the end of 120h and was considered as best formulation. In vitro antibacterial activity was carried out on Streptococcus Mutans.
Barat R., Srinatha Anegundha et al., (2007)8Prepared chitosan based metronidazole inserts were fabricated by the casting method and charactorized with respect to mass and thickness uniformity, metronidazole loading and in vitro metronidazole release kinetics. The fabricated inserts exhibited satisfactory physical characteristics the mass of inserts was in the range of 5.63 ± 0.42 to 6.04±0.89 mg. The thickness ranged from 0.46 ±0.06 to 0.49 ±0.08 mm.Metronidazole loading was in the range of 0.98 ±0.09 to 1.07±0.07 mg except for batch CM3 with MZ loading of 2.01V± 0.08 . The inserts exhibited an initial burst release at the end Of 24 hr, irrespective of drug to polymer ratio plasticizer content or cross linked. However further drug release was sustained over the next 6 days , cross linking With 10%(m/m) of glutaraldehyde inhibited the burst release by~30 % and increased the mean dissolution time (MDT) from 0.67 to 8.59 days .The decrease In drug release was a result of reduced permeability of chitosan due to cross Linking.
Senel S, IkicI G, etal., (2007)9 developed the formulation containing chitosan for local delivery of chlorhexidine gluconate (chx) to the oral cavity. Gels at (1or2% concentration) or film forms of chitosn were prepared containing 0.1-0.2%chx (chlorhexidine gluconate) and their in vitro release properties were studied. The antifungal activity of chitosan itself as well as their various formulations containing chlorhexidine gluconate (chx) was also examined. Release of chlorhexidine gluconate (chx) from gels was maintained for 3hr.A prolong release was observed with film formulation .No lag time was observed in release of chx from either gels or films.The highest antifungal activity was obtained with 2% chitosan gel containing 0.1% chlorhexidine gluconate (chx.).
Hong Hua, Chi ping, et al., (2007)10Prepared multilayer membranes which were loaded with drug for guided tissue regeneration were prepared using an immersed precipitation phase inversion technique, single layer, bilyer and trilayer mechanism were fabricated withchitosan used as carrier and tinidazole as medicine model which was loaded on the membrane. The influence of layer on structure and properties of membrane were studied by SEM, UV spectrometer and mechanical test. Drug release properties of three types of layer membrane also investigated .The result showed that release rate could be shown in both bilayer and trilayer membrane (11 days and 14 days respectively )and trilayer membrane lastest the longest.
ENCLOSURE-III
6.3 Objectives of the study:
The purpose of the study is -
1. To develop a chitosan/poly e caprolactone inserts containing Gemifloxacin.
2. To cross link the prepared inserts for extending the drug release.
3. Evaluation of prepared inserts for physical characteristics such as thickness, tensile strength, folding endurance, content uniformity and weight variation.
4. To study the in-vitro drug release pattern of the drug dosage forms before and after cross linking.
5. To study the drug-polymer interactions by using DSC and FT-IR
6. To carry out the stability studies at different temperature.
7. In-Vitro antibacterial activity.
ENCLOSURE-IV
07. Materials and methods:
7.1 Source of Data:
References from library - S.C.S. college of pharmacy, harapanahalli-583131.
Textbook and standard reference books.
Internet-
National and international journals and publications.
Medline
Helinet for the RGUHS
ENCLOSURE-V
7.2 Methods of collection of data (including sampling proceduresif any)
- From the available literature.
- Attempts will be made to design chitosan/ poly e caprolactone inserts containing gemifloxacin by solvent casting method.
- Attempts will be made to cross link the prepared inserts by using
Glutaraldehyde/TPP (tripolyphosphate pentasodiumsalt) and optimization.
- Prepared inserts will be evaluated for-
Thickness.
Weight variation.
Folding endurance.
Tensile strength and percentage elongation.
Moisture content determination.
Drug content and content uniformity.
In-vitro drug release pattern by using static dissolution test apparatus.
Stability studies.
- Thickness: The thickness of polymer strips (4×4cm) is determined by using digital screw gauge (Mitutoyo).
- Weight variation: Twenty strips of same size (7×2mm) are weighed on electronic balance and average weight will calculate.
- Tensile strength Tensile strength of the films is determined byUniversal strength testing machine.
- Drug content and content uniformity: The drug loaded strips of known weight and dimension is shaken until it dissolved. The drug solution will suitably dilute with buffer and absorbance is measured.
- In-vitro drug release pattern by using static dissolution test apparatus: A static dissolution method reported in the literature will adopt in this method. Sets of six strips of know weight and dimension (7×2 mm) are placed in a small test tube containing 1ml off phosphate buffer, pH.6.6.The tubes are sealed and kept at 37 o C for 24 hours .The buffer medium is then drained off and replaced with a fresh 1ml phosphate buffer pH6.6. The concentration of drug in the buffer is measured
- Stability studies: The stability of drug loaded strips are studied at different temperature and at ambient humid condition, at room temperature (27±2oc) ,oven temperature (40±2oc) and in refrigerator (5-8oc) for a period of 3 months. The samples are analyzed for physical changes and drug content.
ENCLOSURE-VI
08. List of references
1)PattnaikSnigdha, Lalatendu Panigrahi and Rayasa S.R. Murthy1, Periodontal
Muco-Adhesive Formulations for the Treatment of Infectious Periodontal
Diseases. 2007; 4(4):306-323.
2)Bansal.MK, Rawat, et al. Development of Satranidazole Mucoadhesive Gel
for the Treatment of Periodontitis- AAPS PharmSciTech.2009;10(3):716.
3)
4) Mohammed Gulzar Ahmed, Charyulu R N et al., Formulation and in-vitro
evaluation of chitosan films containing tetracycline for the treatement of
Periodontitis.Asian Journal of Pharmaceutics. 2009; 3(2):113-119.
5) Prabhushankar GL,Gopalkrishna B, et al.Formulation and evaluation of
Levofloxacin dental films for periodontitis desease. International Journal of
Pharmacy and Pharmaceutical Sciences.2010; 2(1):162-166.
6) Mohammed Gulzar Ahmed, Harish NM, et al. Formulation of chitosan-based
ciprofloxacin and diclofenac film for periodontitis therapy. Tropical Journal of
Pharmaceutical Research. 2009; 8(1):33-4.
7) MastiholimathVS, DandagiPM, et al. Formulation and evaluation of
ornidazole dental implants for periodontitis. Indian Journal of Pharmaceutical
science. 2006;68(1):68-71.
8)BaratRomi, SrinathaAnegundha, et al.Chitosan inserts for periodontitis:
influence the drug loading plasticizer and cross linking on invitro metronidazole
release Acta -pharma.2007; 57:469-477.
9) Senel SG, Ikinci.et al. Chitosan films and hydrogels of chlorhexidine gluconate
for oral mucosal delivery. International Journal of Pharmaceutics 2000;193:197-203.
10) Hong Hua, CHI ping, LIU Changsheng. Fabrication and properties of multilayer
Chitosan membrane loaded with Tinidazole. Journal of Wuhan University of
technology-Mater sci.2007; 22(1):102-7.