DEVELOPMENT OF SUSTAINED RELEASE MUCOADHESIVE FLOATING TABLETS OF CLARITHROMYCIN FOR H.PYLORI ERADICATION
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BY
TANVEER KHAN
B.Pharm.
UNDER THE GUIDANCE OF
DR.DEHGHAN MOHAMMED HUSSAN
M.Pharm.,Ph.D
Professor
PG Dept. of Pharmaceutics
DEPARTMENT OF PHARMACEUTICS
LUQMAN COLLEGE OF PHARMACY
GULBARGA-585102
2012-2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
Name of the Candidate and Address (In block letters) / TANVEER KHANAT+P.O-MAJHARIA, V.I.A-RAMGARHWA
P.S-ADAPUR, DISTRICT-EAST CHAMPARAN
STATE-BIHAR, PIN-845433
Name of the Institution / Luqman College of Pharmacy,
P & T COLONY,OLD JEWARGI ROAD,
gULBARGA – 585 102
Course of Study and Subject / M.PHARM (PHARMACEUTICS)
Date of Admission to Course / 29/06/2012
Title of the Research Topic / DEVELOPMENt OF SUSTAINED RELEASE MUCOADHESIVE FLOATING TABLETS OF CLARITHROMYCIN FOR H.PYLORI ERADICATION
6. Brief resume of the intended work
6.1. Need for the study
Floating Drug delivery system (FDDS) are designed to prolong the gastric residence time after oral administration, at particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability. Improved drug absorption, because of increased GRT and more time spent by the dosage form at its absorption.1 Floating systems are the low-density systems that have sufficient buoyancy to float over gastric contents and remain in the stomach for a prolonged period. While the system floats over gastric contents, the drug release slowly at the desired rate.2
Helicobacter pylorus (H.pylori) is a Gram-negative, motile, microaerophilic spiral bacterium. Helicobacter species cause peptic ulcer disease. Gastric (mainly peptic) ulcer is one of major aliments affecting about 60% of human adults and nearly 80% of child population, all H.pylori species cause some degree of persistent inflammation .3
Clarithromycin is a macrolide antibiotic widely prescribed in H.pylori mediated peptic ulcers, upper respiratory tract infections. The recommended adult oral dosage of clarithromycin is 500 mg twice daily for the effective treatment of H.pylori caused peptic ulcer. The biological half life of drug is 3–5 h and the oral bioavailability of clarithromycin is 55%.4 Clarithromycin is stable in gastric acidic medium and has a narrow absorption window in gastrointestinal tract, rapid gastrointestinal absorption, highly soluble at acidic pH.5
In the present work sustained release mucoadhesive floating tablets of clarithromycin will by prepared by using different natural and synthetic hydrogel forming polymers along with oil or bicarbonates as a floating carriers.
6.2 Review of the literature
Literature survey was carried out on the proposed research work by referring various scientific research journals, internet and Helinet facilities, no work has been reported on the proposed research topic and few articles related to the topic are listed below.
1. Nallasamy V. et al6 prepared floating microspheres by emulsion solvent evaporation technique. These microspheres stay in stomach for prolonged periods and could ensure the stability of amoxicillin in gastric environment, which eventually resulted in better eradication of H. pylori than the conventional dosage forms.
2. Kotwal A. et al7 prepared floating tablets of amoxicillin by wet granulation technique. The prepared intragastric buoyant tablets of amoxicillin will provide site-specific drug delivery and there by extend its duration of action.
3. Singh PK, et al8 prepared floating tablets of clarithromycin using sodium CMC, carbopol974P and sodium alginate as bioadhesive polymers to impart mucoadhesion.
4. Laxmikant RZ, et al3 prepared floating mucoadhesive tablets of clarithromycin for the treatment of H.pylori infection. Tablets were prepared by direct compression method using directly compressible polymers such as HPMC K4M, HPMC K15M and carbopol 974P.
5. Tripathi GK, et al9 prepared pectin based oil entrapped micro gel floating beads by ionic gelation technique using castor oil and mineral oil. The results provides evidence that optimized gel bead may be used to incorporate antibiotics like amoxicillin and may be effective when administered locally in the stomach to cure microbial infection.
6. Sheela N.B.S, et al5 prepared floating sustained release tablets of clarithromycin by using a combination of hydrophilic polymers (different grades of hydroxypropyl methylcellulose), kollidon SR and an effervescent substance (sodium bicarbonate). The drug release of optimized formulation was found to follow Zero order, Higuchi and Korsmeyer‐Peppas kinetic models.
7. Arya R.K.K, et al10 prepared gastro resistant double walled floating microspheres. The primary wall composed of mucoadhesive polymer sodium CMC and a release controlling polymer sodium alginate. The second wall coating the primary microspheres was composed of eudragit S-100.
8. Singh PK, et al.6 prepared gastroretentive floating matrix tablets of clarithromycin which were prepared by direct compression method using hydroxypropyl methylcellulose K4M (HPMC K4M ), HPMC K15M, HPMC K100M, with sodium bicarbonate as gas forming agent.
9. Nama M, et al.4 prepared floating tablets by wet granulation method loaded with barium sulphate to justify the increased gastric residence time in vivo. The formulations developed by using 66.2% clarithromycin, 12% HPMC K4M, 8% sodium bicarbonate give floating lag time less than 3 min with a floating time of 12 h.
10. Tejaswi BS, et al.2 prepared floating microspheres of clarithromycin were prepared by solvent evaporation technique using ethyl cellulose as a polymer. It was concluded that the required amount of clarithromycin for eradication of H.pylori was significantly less in microspheres than from corresponding clarithromycin suspension.
11. Nimase PK, et al.11 prepared multiple-unit floating beads of clarithromycin using sodium alginate solution containing hydroxypropyl methylcellulose K100M and sunflower oil by emulsion gelation method. These beads were evaluated for entrapment efficiency, drug loading, buoyancy and in vitro drug release.
12. Dinesh BG, et al.12 prepared metronidazole floating dosage forms that retain in the stomach for a long time and have better eradication of H.pylori in peptic ulcer diseases. Hydroxy propyl methyl cellulose (HPMC) and sodium alginate in different concentrations were used as mucoadhesive agents and sodium bicarbonate and citric acid as effervescent agents.
13. Radhakrishna M, et al.13 prepared floating matrix tablets of amoxicillin trihydrate with different natural and synthetic polymers such has HPMC K4M, HPMC K15M, HPMC K100M by taking single polymer in the formulation. Thus the concentration and resident time of amoxicillin trihydrate in stomach would be effective for complete eradication of H.pylori.
6.3 Objectives of study:
The aim of present work is to prepared sustained release mucoadhesive floating tablet of
clarithromycin so as to prolong residence time in stomach to effectively eradicate H.pylori
and to improve the bioavailability. The main objective are;
1) To develop sustain release mucoadhesive floating tablets of clarithromycin by using different natural and synthetic hydrogel polymers along with oil or bicarbonate as floating carriers.
2) To study the physico-chemical interaction of polymers-drug by FTIR spectroscopy and DSC.
3) To evaluate the prepared tablets for tableting properties like weight variation, hardness, friability, drug contents.
4) To study the invitro buoyancy time, invitro mucoadhesion and invitro release of drug.
5) To study the effect of concentration of oil or bicarbonate on invitro buoyancy time and to study the effect of different polymer or polymer concentration on mucoadhesion and in vitro release.
7. Materials and methods
7.1 Materials:
Drug: Clarithromycin
Polymers: chitosan / sodium alginate / guar gum / xanthan gum / hydroxy propyl methyl cellulose / carbopol / pectin etc.
Other excipients: Bicarbonates like sodium/calcium bicarbonates or fixed oils like vegetable oil.
Equipments:
1. UV/ Visible spectrophotometer 1700 (Shimadzu)
2. Digital PH mater
3. Digital Over head stirrer
4. Electronic Balance (Shimadzu Corporation BL-220H Pune)
5. Thermostatic hot plate with magnetic stirrer (Remi motors. Mumbai)
6. Hot air oven
7. Elecrolab dissolution apparatus (USP XXIII)
8. IR spectrophotometer (JASCO/FT/IR-5300)
9. Tablet compression machine (Remek)
10. Hardness tester (Monsanto)
7.2 Methods:
1. UV/ vvisible spectrophotometric estimation of clarithromycin.
2. Physico-chemical interaction of drug with polymers and other excipient by FTIR Spectroscopy and DSC.
3. Sustained release mucoadhesive floating tablets of clarithromycin will be prepared by direct compression method using single station tableting machine.
4. Evaluation of prepared floating tablets for weight variation, drug content, hardness, thickness, friability, in vitro mucoadhesion, in vitro dissolution study, in vitro buoyancy.
7.3 Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please described briefly.
------Not under the plan of our work ------
7.4 Has ethical clearance been obtained from your institution in case of 7.2
------Not Applicable ------
8. LIST OF REFERENCES :
1. Bhowmik D, Chiranji B, Chandira M, Jayakar B, Sampth K.P.K. “floating drug delivery system”. Der Pharmacia Lettre, 2009; 1(2): 199-218.
2. Tejaswi BS, Sivadasan D, Phalini DP. Formulation and in vitro evaluation clarithromycin floating microspheres for eradication of H.pylori. Der Pharmacia Lettre, 2011; 3(6): 90-101.
3. Laxmikant RZ, Pankaj JS, Sanjay BB, Surendra GG. Formulation and evaluation of floating mucoadhesive tablet of clarithromycin.” IJPBS, 2010; 1(2): 1-10.
4. Nama M, Gonugunta CSR, Veerareddy PR.Formulation and evaluation of gastroretentive dosage forms of clatithromycin.”AAPS Pharm Sci Tech, 2008; 9(1): 231-237.
5. Sheela NBS, Damodharan N, Madhukar BS, Surekha I, Srinivas RT. Formulation and evaluation of clarithromycin gastroretentive dosage form. IJPPS, 2010; 2(3): 48-55.
6. Nallasamy V, Sambathkumar P. Formulation and evaluation of stomach specific amoxicillin loaded mucoadhesive microspheres. Iranian Journal of Pharmaceutical Sciences, 2010; 6(4): 227-233.
7. Kotwal A,Pathak AK. Formulation and evaluation of intragastric buoyant gastric tablets of amoxicillin trihydrate. Int. J. of Pharm. & Life Sci 2011;2(2):546-50.
8. Singh PK. “Formulation development and evaluation of mucoadhesive oral dosage form containing clarithromycin using different mucoadhesive polymers.” 2012; 2(2): 159-171.
9. Tripathi GK, Singh S. Formulation and In-vitro evaluation of pH sensitive oil entrapped buoyant beads of amoxicillin. International Journal of Drug Delivery 3 , 2011; 125-132.
10. Arya R.K.K, Juyal V, Singh R. “Development and evaluation of gastroresistant microspheres of pentoprazole . Int J Pharmacy and Pharm Sci, 2010; 2(3): 112-116.
11. Nimase PK, Vidyasagar G. Preparation and evaluation of floating calcium alginate beads of clarithromycin. Der Pharmacia Sinica, 2010; 1 (1): 29-35.
12. Dinesh BG, Chandra SR, Devi AS, Reddy BVV, Latha NS. Formulation and evaluation of novel effervescent metronidazole floating tablets. 2011; 2(4): 1657-1662.
13. Radhakrishna M, Parthiban KG, Ramarao N, Deepika NS, Abhishek P. Formulation and evaluation of floating drug delivery system of amoxicillin trihydrate. IRJP, 2012; 3(8): 233-237.
9. Signature of the Candidate / (TANVEER KHAN)
10. Remarks of the Guide: / The proposed research work may improve the therapeutic efficacy of the drug by increased in GI residence time and by controlled release. Hence recommended for registration.
11. Name & Designation (in BLOCK LETTERS)
11.1 Guide / Dr. DeHghan MohammEd Hussan
Professor
Department of pharmaceutics,
Luqman College of Pharmacy,
GULBARGA. KARNATAKA.
11.2 Signature of Guide
11.3 Co-Guide
11.4 Signature of Co-Guide
12.1 Remark of the principal / We will provide all the necessary facilities required for the proposed research work. So, recommended for registration.
12.2 Signature of principal
9. / Signature of Candidate / (TANVEER KHAN)
10. / Remarks of the Guide / The Proposed Research topic is Chosen with a hope that, it may improve the therapeutic efficacy of the drug with the increased G.I retention time and by controlled release.
So, recommended for registration.
11. / Name and Designation of
(in block letters)
11.1 / Guide / M.A.SALEEM
M. Pharm.
PROFESSOR & H.O.D.
P.G. DEPARTMANT OF PHARMACEUTICS
LUQMAN COLLEGE OF PHARMACY,
P & T COLONY,OLD JEWARGI ROAD,
GULBARGA.
11.2 / Signature
11.3 / Co-guide
11.4 / Signature
12. / 12.1 / Remarks of the Chairman & Principal / We will provide all the necessary facilities required for the proposed research work.
So, recommended for registration
12.2 / Signature
9. / Signature of Candidate / (TANVEER KHAN)
10. / Remarks of the Guide / The Proposed Research topic is Chosen with a hope that, it may improve the therapeutic efficacy of the drug with the increased G.I retention time and by controlled release.
So, recommended for registration.
11. / Name and Designation of
(in block letters)
11.1 / Guide / M.A.SALEEM
M. Pharm.
PROFESSOR & H.O.D.
P.G. DEPARTMANT OF PHARMACEUTICS
LUQMAN COLLEGE OF PHARMACY,
P & T COLONY,OLD JEWARGI ROAD,
GULBARGA.
11.2 / Signature
11.3 / Co-guide
11.4 / Signature
12. / 12.1 / Remarks of the Chairman & Principal / We will provide all the necessary facilities required for the proposed research work.
So, recommended for registration
12.2 / Signature
9. / Signature of Candidate / (TANVEER KHAN)
10. / Remarks of the Guide / The Proposed Research topic is Chosen with a hope that, it may improve the therapeutic efficacy of the drug with the increased G.I retention time and by controlled release.
So, recommended for registration.
11. / Name and Designation of
(in block letters)
11.1 / Guide / M.A.SALEEM
M. Pharm.
PROFESSOR & H.O.D.
P.G. DEPARTMANT OF PHARMACEUTICS
LUQMAN COLLEGE OF PHARMACY,
P & T COLONY,OLD JEWARGI ROAD,
GULBARGA.
11.2 / Signature
11.3 / Co-guide
11.4 / Signature
12. / 12.1 / Remarks of the Chairman & Principal / We will provide all the necessary facilities required for the proposed research work.
So, recommended for registration
12.2 / Signature
9. / Signature of Candidate / (TANVEER KHAN)
10. / Remarks of the Guide / The Proposed Research topic is Chosen with a hope that, it may improve the therapeutic efficacy of the drug with the increased G.I retention time and by controlled release.
So, recommended for registration.
11. / Name and Designation of
(in block letters)
11.1 / Guide / M.A.SALEEM
M. Pharm.
PROFESSOR & H.O.D.
P.G. DEPARTMANT OF PHARMACEUTICS
LUQMAN COLLEGE OF PHARMACY,
P & T COLONY,OLD JEWARGI ROAD,
GULBARGA.
11.2 / Signature
11.3 / Co-guide
11.4 / Signature
12. / 12.1 / Remarks of the Chairman & Principal / We will provide all the necessary facilities required for the proposed research work.
So, recommended for registration
12.2 / Signature