“DESIGN AND evaluation of CONTROLLED GASTRo retentive drug delivery system OF MOXIFLOXACIN”
DISSERTATION PROTOCOL
Submitted to the
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
BY
A. JANARDHANA REDDY
M.Pharm, Part-1
DEPARTMAENT OF PHARMACEUTICS
UNDER THE GUIDANCE OF
Dr. R.RAMESH, M.Pharm.,Ph.D
Department of Pharmaceutics,
Dr. H.L.T College of Pharmacy,
Kengal, chennapatna -562 161
Ramanagaram (Dist), Karnataka.
2011-2012
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE, BANGALORE, KARNATAKA.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate andAddress (In Block Letters) / A.JANARDHANA REDDY
M. PHARM, PART-I
DEPARTMENT OF PHARMACEUTICS
Dr. H. L. T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-562 161
RAMANAGARAM DIST. KARNATAKA.
2. / Name of the Institution / Dr. H. L. T. COLLEGE OF PHARMACY,
KENGAL, CHANNAPATNA-562 161
RAMANAGARAM DIST. KARNATAKA
3. / Course of the Study and
Subject / MASTER OF PHARMACY IN PHARMACEUTICS
4. / Date of Admission to the
Course / 06-07-2011
5. / Title of the Topic / “DESIGN and evaluation of CONTROLLED GASTRo retentive drug delivery system of MOXIFLOXACIN”
6. BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY:
Gastric ulcers1 are induced due to many factors like excessive intake of alcohol, chronic smoking, irregular dietary habits, influence of external and internal stress factors, other factors like bacterial infection caused due to helicobacter Pylori.The current therapy involves administration of antacid preparations, proton pump inhibitors, H2–receptor antagonists & surgery as last option, parallel therapy with antibiotics is recommended if the ulcers are induced due to bacterial infection.
The present study is aimed to design a controlled gastric floating drug delivery system (CFDDS) incorporating antibiotic drug like moxifloxacin to cure bacterial infection caused due to helicobacter pylori, respiratory infection, Cellulitis, anthrax, Intraabdominal infection. In the adult population its oral and intravenous is limited to the treatment proven serious and life-threatening bacterial infections. It may also show benefit for the maintenance treatment of meningitis, the treatment of duodenal and gastric ulcers, the prevention of gastro-duodenal damage in patients taking NSAIDs, and as adjunctive therapy with antiulcerative drugs for the eradication of Helicobacter pylori.
FDDS is chosen as it has site specific drug delivery, long resident time in stomach is achieved and offers prolonged drug release GFDDS are buoyant tablets which release co2, swell & float in gastric fluid & remain as such for long duration & release the drug in a controlled manner as polymers are used .so, once a day (OD) dose can be designed for effective and prolonged therapy throughout the day and offers patient compliance.
Floating tablets2 are novel dosage forms wherein drug delivery is controlled by diffusion through polymers, therefore this work is planned to formulate controlled release floating tablet using drug like Moxifloxacin, is a fourth-generation synthetic fluoroquinolone antibacterial agent and evaluate the tablet for its floating ability, hardness, friability, drug release rate, buoyancy etc. it is also planned to conduct stability studies at different temperature and humidity.
Floating drug delivery system provides better bioavailability for the drugs that are unstable in intestinal or colonic environment3
Based on the mechanism of floatation, delivery system can be classified into two types
1. effervescent floating drug delivery system
2. Non- effervescent floating drug delivery system4.
Advantage of floating drug delivery system are5
1. Site specific drug delivery
2. Patient compliance
6.2 Review of literature:
1. S N borkar, R suresh, VA sawant, VS shende, VJ mokale, G dama , were given an approach to formulate bilayered gastro retentive floating drug delivery system of cefpodoxime proxetil and evaluated for floating lag time, compatibility studies , bioavailability studies, total floating time and in-vitro study by using different polymers and evaluated that the drug released decreases with an increase in polymer concentration4.
2. Shoufeng Li, Senshang Lin, Bruce P. Daggy, Haresh L. Mirchandani, Yie W. Chien , were described about Effect of Formulation Variables on the Floating Properties of Gastric Floating Drug Delivery System (GFDDS) using a continuous floating monitoring system and statistical experimental design methods, which consisted of an electric balance interfacing with a PC, was designed to perform the continuous monitoring of floating kinetics of GFDDS. Several formulation variables, such as different types of hydroxyl propyl methyl cellulose (HPMC), varying HPMC/Carbopol ratio, and addition of magnesium stearate, were evaluated using Taguchi design, and the effects of these variables were subjected to statistical analysis. The combination of HPMC and Carbopol polymer shows good results.6
3. Nirav S sheth, Rajan b mistry , worked on formulation and evaluation of floating drug delivery system of Clarithromycin, to achieve controlled plasma level and improving bioavailability , for the treatment of H. Pylori infection by using HPMC as a polymer. This study shows that tablet composition and mechanical strenghth have great influence on floating properties and Drug release5.
4. S.C.Basak et al, were studied formulation and evaluation of an Oral Floating Matrix tablet of Ciprofloxacin and evaluated as Ciprofloxacin being absorbed well in stomach and upper small intestine was formulated as floating matrix tablets using gas generating agent (sodium bicarbonate) and hydrophilic polymer Hydroxy propyl methyl cellulose (HPMC). Formulation was optimized on the basis of floating time and in-vitro drug release. Two batches of fabricated tablets containing Ciprofloxacin(580 mg), Sodium bicarbonate (200mg), Hydroxypropylmethylcellulose-K100M (100 mg), lactose 9.7-12% and polyvinyl pyrrolidine 4.8% having hardness between 14-14.6% kg/cm2. Showing floating time of about 8 hrs and more.The drug release rate was about 80-89% at the end of 8 hours. Thus showing that gas powered floating matrix tablet is a promising gastric floating delivery system.8
5. Arunachalam.A , B.stephen rathinary, Ch.Rajveer, D. kumarswamy, A.M.umarunnisha , worked on Design and evaluation of Levofloxacin Hemihydrate floating tablets which is done by Melt granulation method using HPMC K100M with different amount of excipients , for sustained release drug delivery system. Levofloxacin tablets drug delivery system showed improved in-vitro bioavailability and extended drug release which may favour the reduced dose frequency and patient compliance6.
6. Sharma S, et al, were developed low density multiparticulate system for pulsatile release of Meloxicam they combined the principles of floating and pulsatile drug delivery system. they prepared multiparticulate floating pulsatile drug delivery system using porous calcium silicate and sodium alginate for the time and site specific drug release of Meloxicam.11
7. EL-Kamal, A.H, et al, were prepared and evaluated Ketoprofen floating oral delivery system the designed sustained release system for Ketoprofen to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microparticles by the emulsion solvent diffusion technique. they used four different ratio of eudragit S100 with eudragit RL to form the floating microparticals. it was found that release rates were generally low in 0.1N Hcl especially in presence of high content of eudragit S.100 while in phosphate buffer PH 6.8, high amounts of eudragit S 100 tended to give a higher release rate.12
8. Streubel A. et al, were prepared floating microparticles consisting of (1) polypropylene foam powder (2) Verapamil Hcl as model drug and (3) eudragit RS, ethyl cellulose (EC) or polymethyl methacrylate (PMMA) as polymers were prepared with an o/w solvent evaporation method. The effect of various formulation and processing parameters on the internal and external particle morphology, drug loading in-vitro floating behaviour in vitro drug release kinetics, particle size distribution and physical state of the incorporated drug was studied. They reported that the type of significant affected the drug release rate, which increased in the following rank under PMMA<EC< eudragit RS.13
9. Ravindra S dhumal, Samitkumar T rajmane, Sanjay T dhumal ,were worked on design and evaluation of Bilayered floating tablets of Cefuroxime Axetil for bimodal release. Which showed that bimodal drug release comprising of immediate release for quick one-set of action followed by controlled release minimizing concentration of unabsorbed drug entering colon was achieved7.
6.3 MAIN OBJECTIVES OF THE STUDY:
In this present investigation we propose:
- To formulate Gastric Floating tablet using polymers like Hydroxy Propyl Methyl Cellulose (HPMC) , Ethyl Cellulose (EC), Na CMC, NaHCO3 Effervescent mixtures.
- To evaluate pre- compression and post-compression parameters.
- To evaluate its floating properties like floating lag time, floating time, buoyancy.
- To perform in-vitro dissolution studies.
- To evaluate the stability studies according to ICH guidelines.
- Drug interaction studies by FTIR and DSC.
7. MATERIALS AND METHODS:
1. Materials:
Moxifloxacin,Ethylcellulose,Sodium carboxy methylcellulose,Sodium bicarbonate etc.
2. Methods:
Wet granulation,Dry granulation or Direct compression method.
7.1 SOURCE OF DATA:
The preliminary data required for the experimental study is obtained from .
- CD-Rom search available at national center for scientific information (NCSI), Indian institute of Sciences, Bangalore.
- Journal
- Analytical chemistry Books
- Library
- Relevant Books
- Internet Source
- Scientific abstracts.
7.2 METHODS OF COLLECTION OF DATA :
1. The selected drug will be characterize for various physicochemical properties like organoleptic properties, solubility etc.
2. an analytical method for estimation of drug will be developed and validated using U.V Spectrophotometer (UV-1700,SHIMAZDU,JAPAN)
3. Formulation of Floating tablets by using various polymers like different grades of HPmC, Carbapol, EC etc.,
4. the various powder characteristics like bulk density, angle of repose, carr’s index, compressibility index etc.., will be evaluated.
5. tablets will be compressed on ten station rotary tablet compression machine (REMIC INDIA, Ahmedabad ) and evaluated for floating time, weight variation, content uniformity etc.
6. the effect of polymers and their ratios on drug release will be studied.
7. in-vitro dissolution studies will be carried out using USP Dissolution Apparatus (DISSO
2000, LAB INDIA).
7. Stability studies will be carried out according to ICH guidelines.
8. All the data obtained will be subjected for statistical analysis.
7.3 Does the study require any investigation to be conducted on patients/Humans /
animals? If so, please briefly
noT APPLICABLE
7.4 Has ethical clearance been obtained from your institution in case of 7.3
NOT APPLICABLE
8. LIST OF REFERENCES:
1. http://www.medicinenet.com/peptic_ulcer/page4.htm
2. AroraS,AliJ,AhujaA,KharRK,BabootaS.Floating Drug Delivery Systems: A Review.AAPS PharmSciTech, 2005;06(03):E372-E390.
3. Dave BS Amin AF Patel M., Gastro retentive drug delivery system of Ranitidine Hcl formulation and in-vitro evaluation. AAPS pharmaSciTech, 2002; 5:1-10
4. S N borkar, R suresh, VA sawant, VS shende, VJ mokale, G. dama, Bilayered gastro retentive floating drug delivery system of cefpodoxime, international journal of chemtech research codon USA, 2010; 2 (2):1229-1242.
5. Nirav S sheth, Rajan B mistry, Formulation and evaluation of floating drug delivery system of clarithromycin, international journal of pharmaceutical and biosciences, 2011; 2(1) :571-580.
6. Arunachalam .A, B.stephen rathinary, Ch. Rajveer, D. kumaraswamy, A. M. umarunnisha, Design and evaluation of levofloxacin floating tablet, International journal of applied biology and pharmaceutical technology, 2010;1(2):260-268.
7. Ravindra S dhumal, Samithkumar T rajmane, Sanjay T dhumal, Design and evaluation of Bilayered floating tablet of Cefuroxime Axetil for bimodal release, Journal of scientific and industrial research, 2006;65:812-816.
8. S.C.Basak, et al, Development and in-vitro evaluation of an Oral Floating Matrix tablet Formulation of Ciprofloxacin, Indian.J.Pharm.Sci, 2004; 66(3):313-316.
9. K. Himasankar,et al, Design and Biopharmaceutical evaluation of Gastric floating Drug Delivery System of Metformin Hydrochloride. Indian J.Pharm Edu & Research, 2006;40 (1):61-62.
10. Kale RD , Tayade PT . A multiple unit drug delivery system of Pyroxicam using eudragit polymer, Indian J. Pharma sci, 2007; 69 (1):120-23.
11. Sharma S, Pawar A. Low density multipurticulate system for pulsatile release of Meloxicam Current drug delivery, 2006; 3:87-96.
12. EL-Kamel AH , Sokar MS, Al Gamal SS, Naggar VF, Preparation and evaluation of Ketoprofen floating oral delivery system. Int J pharmaceutics, 2001; 220:13-21.
13. Streubel A, Siepmann J, Bodmeier R, Floating microparticles based on low density foam powder. Int. J. pharma, 2002; 241 (2):279-92.
14. P.G Yeole, Shaguftha khan and V.F Patel, Floating drug delivery system Need and development, Ind.J. Pharm, 2006;7(3):265-272.
15. Patel DM, Patel NM, Patel VF, Bhatt DA. Floating Granules of Ranitidine hydrochloride Geliucire 43/01. Formulation optimization using factoral design ,AAPS pharma Sci Tech, 2007;8(2):22-24.
16. SinghBN,KimKH.Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention.J Control Release.2000;63:235-259.
17. TimmermansJ,AndreJM.Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy.J Pharm Sci.1994;83:18-24.
18. DesaiS,BoltonS.A floating controlled release drug delivery system: in vitro- in vivo evaluation.Pharm Res.1993;10:1321-1325.
19. YangL,EsharghiJ,FassihiR.A new intra gastric delivery system for the treatment of helicobacter pylori associated gastric ulcers: in vitro evaluation.J Control Release.1999; 57:215-222.
20. ChoiBY,ParkHJ,HwangSJ,ParkJB.Preparation of alginate beads for floating drug delivery: effects of CO2 gas forming agents.Int J Pharm.2002; 239:81-91.
21. LiS,LinS,DaggyBP,MirchandaniHL,ChienTW.Effect of formulation variables on the floating properties of gastric floating drug delivery system.Drug Dev Ind Pharm.2002; 28:783-793.
22. LiS,LinS,ChienTW,DaggyBP,MirchandaniHL.Statistical optimization of gastric floating system for oral controlled delivery of calcium.AAPS PharmSciTech.2001; 2:E1.
23. ThanooBC,SunnyMC,JayakrishnanA.Oral sustained release drug delivery systems using polycarbonate microspheres capable of floating on the gastric fluids.J Pharm Pharmacol. 1993; 45:21-24.
24. StreubelA,SiepmannJ,BodmeierR.Floating matrix tablets based on low density foam powder: effect of formulation and processing parameters on drug release.Eur J Pharm Sci.2003; 18:37-45.
25. ErniW,HeldK.The hydrodynamically balanced system: a novel principle of controlled drug release.Eur Neurol, 1987; 27:215-220.
26. ShethPR,TossounianJ.The hydrodynamically balanced systems (HBS): a novel drug delivery system for oral use.Drug Dev Ind Pharm.1984;10:313-339.
27. HiltonAK,DeasyPB.In-vitro and in-vivo evaluation of an oral sustained release floating dosage form of Amoxycillin trihydrate.Int J Pharm, 1992; 86:79-88.
28. J.Timmermans and A.J Moes, How well do floating dosage forms float, Int.J.pharm, 1996; 62:207-216.
9. / Signature of the candidate10. / Remarks of the Guide / Topic selected for Dissertation work is satisfactory.
This can be carried out in our Laboratory.
11. / Name and Designation of
(In Block Letters)
11.1 Guide
11.2 Signature / Dr. R.RAMESH, M.Pharm., Ph.D
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
Dr. H.L.T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA- 562 161
RAMNAGARAM (DIST), KARNATAKA.
11.3 Co-Guide (If any)
11.4 Signature / ------
11.5 Head of the Department
11.6 Signature / Dr. R. RAMESH. M.Pharm., Ph.D
PROFESSOR,
DEPARTMENT OF PHARMACEUTICS
Dr. H.L.T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA-562161
RAMNAGARAM (DIST), KARNATAKA.
12 / 12.1 Remarks of the
Chairman and Principal
12.2 Signature / The above mentioned information is correct and recommend the same for approval.
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