FORMULATION AND EVALUATION OF ANTIBIOTIC GASTRIC FLOATING DRUG DELIVERY SYSTEM
DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
BY
ASHOK KUMAR.I
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDENCE OF
Mrs. THAHERA PARVEENMRAZIR ASHFAQ AHMED
DEPARTMENT OF PHARMACEUTICS
M.M.U. COLLEGE OF PHARMACY
RAMANAGARAM-571511
KARNATAKA
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE- II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATE AND ADDRESS (IN BLOCK LETTERS) / ASHOK KUMAR .IS/O VENKATESWARA REDDY,
H.NO.1-131, OLD TOWN, KANIGIRI, PRAKASAM (D.T)
2. / NAME OF THE INSTITUTION / M.M.U COLLEGE OF PHARMACY
RAMANAGARAM-571511
3. / COURSE OF STUDY AND SUBJECT / M.PHARM,
PHARMACEUTICS
4. / DATE OF ADMISSION OF COURSE / 29/6/2009
5. / TITLE OF TOPIC / FORMULATION AND EVALUATION OF ANTIBIOTIC GASTRIC FLOATING DRUG DELIVERY SYSTEM
6. / BRIEF RESUME OF THE INTENDED WORK
6.1 Need For The Study
6.2 Review of the literature
6.3 Objective of the study / ENCLOSURE- I
ENCLOSURE- II
ENCLOSURE-III
7. / MATERIALS AND METHOD
7.1 Source of data
7.2 Method of collection of data
7.3 Does study require any
Investigations or interventions
To be conducted on patients or
Other human or animal? If so,
Please describe briefly.
7.4 Has ethical clearance been
Obtained from your institution in
Case of 7.3 / ENCLOSURE- IV
ENCLOSURE- V
ENCLOSURE-VI
8. / LIST OF REFERENCES / ENCLOSURE-VII
9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF GUIDE / FORWARDED FOR APPROVAL
11. / NAME AND DESIGNATION OF
11.1 Guide / Mrs. THAHERA PARVEENMRAZIR
M.M.U COLLEGE OF PHARMACY
K.K DODDI, RAMADEVERA BETTA ROAD RAMANAGARAM-571511
KARNATAKA
11.2 Signature
11.3 co guide(if any) / Not applicable
11.4 Signature / Not applicable
11.5 Head OF The Department
/ VAZIR ASHFAQ AHAMED
ASST.PROFESSOR
DEPARTMENT OF PHARMACEUTICS,
M.M.U COLLEGE OF PHARMACY
K.K DODDI, RAMADEVERA BETTA ROAD RAMANAGARAM-571511
KARNATAKA
11.6 Signature
12. / 12.1 Remarks Of The
Chairman and Principal
12.2 Signature / SUBMITTED FOR APPROVAL
6 .
/ BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE- I
6.1 Need for the study
Ø Norfloxacin is a second generation synthetic fluoroquinolone chemotherapeutic agent. It has broad spectrum activity and it is effective against Gram-negative and Gram-positive aerobes, it is therapeutically useful for gastrointestinal infections like mild to complicated urinary tract infections, urethral and cervical gonorrhea, diarrohoeas caused due to bacteria, Syphilis, Prostatitis. Norfloxacin possesses a Half life of 3.75 hours and its Bioavailability is 30 to 40%. The therapeutic dose is 400mg t.i.d for 3-7 days depending upon the disease. Hence the present study is to formulate and optimize a controlled release dosage form using Gastric Floating Drug delivery system (GFDDS) using different synthetic and natural polymers, which can provide extended drug release within the therapeutic window for above 24 hours. This dosage form can provide patient compliance and therapeutic efficacy against several mild to complicated disease by improving the bioavailability.
ENCLOSURE- II
6.2 Review of the literature
Ø Bomma Ramesh , et al 1. Floating matrix tablets of Norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using polymers such as hydroxypropyl methylcellulose (HPMC K4M, HPMC K100M) and xanthan gum. Tablets were evaluated for their physical characteristics, viz. hardness, thickness, friability and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium.
Ø Patel VF, et al.6 developed Ranitidine floating tablets; in which they optimized types of filler, different viscosity grades of HPMC and its concentration. Two fillers namely Avicel pH 102 and Tablettose 80 were used. Three different viscosity grades of HPMC namely K100 LV, K4M and K15M were used. The drug release from hydrophilic matrices occurred via diffusion mechanism following square root of time profile (Higuchi equation). Hardness of tablets had greater influence on floating lag time.
Ø Shrivastava AK, et al.7 prepared floating matrix tablets of atenolol to prolong gastric residence time and increase drug bioavailability. The tablets were prepared by direct compression technique,
using polymers such as HPMC K15M, K4M, Guargum (GG), and sodium carboxy methylcellulose (SCMC), alone or in combination, and other standard excipients. In vitro release mechanism was evaluated by linear regression analysis. GG- and SCMC-based matrix tablets showed significantly greater swelling indices compared with other batches.
Ø Fell, et al.8 prepared floating alginate beads by incorporating Amoxycillin. The beads were produced by drop wise addition of alginate into calcium chloride solution, followed by removal of gel beads and freeze-drying. The beads containing the dissolved drug remained buoyant for 20 hours and high drug-loading levels were achieved
Ø Baumgartnar, et al.9 developed a matrix-floating tablet incorporating a high dose of freely soluble drug. The formulation containing 54.7% of drug, HPMC K4 M, Avicel PH 101, and a gas-generating agent gave the best results. It took 30 seconds to become buoyant.
Ø Yang, et al.10developed a swellable asymmetric triple-layer tablet with floating ability to prolong the gastric residence time of triple drug regimen (Tetracycline, Metronidazole, and Clarithromycin) in Helicobacter pylori–associated peptic ulcers using hydroxy propyl methyl cellulose (HPMC) and poly (ethylene oxide) (PEO) as the rate-controlling polymeric membrane excipients. The floating feature aided in prolonging the gastric residence time.
Ø Ziyaur rahman, et al.11 developed a bilayer-floating tablet (BFT) for Captopril using direct compression technology. HPMC, K-grade and effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained captopril and various polymers such as HPMC-K15M, PVP-K30 and Carbopol 934p, alone or in combination with the drug.
Ø Mahesh Chavanpatil, et al.13 prepared sustained release (SR)-gastroretentive dosage forms (GRDF) for Ofloxacin preferably once daily. Different polymers, such as psyllium husk, HPMC K100M, crosspovidone and its combinations were tried in order to get the desired sustained release profile over a period of 24hrs. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines.
ENCLOSURE- III
6.3 Objectives of the study
1. Preparation and evaluation of floating tablet of Norfloxacin that retains in the stomach for 24 hours and improves its bioavailability.
2. Provide an increased gastric residence time resulting in prolonged drug delivery in stomach using different polymers.
3. To study and optimize the various formulations and process variables that ultimately affects the drug release.
4. Selection and optimization of polymer concentration, type of filler and amount of polymer that has pronounced effect on tablet properties and drug release profile as well as buoyant properties of the formulations.
7. MATERIALS AND METHODS
MATERIALS
Drug : Norfloxacin
Polymers : Carbomers, Carboxymethylcellulose ,HPMC,
Ethylcellulose, Xanthan gum,Guar gum,
and other natural gums.
Other Additives : Sodium bicarbonate, Dicalcium phosphate,
Talc, Magnesium stearate,Crosspovidone
METHODS:
The tablets will prepared by direct compression technique and Wet granulation method depending on the compatibility of drug and excepients , using polymers such as HPMC K15M, K4M, Guargum (GG), and sodium carboxy methylcellulose (SCMC), alone or in combination, and other standard excipients, to optimize the formulation.
1) Preformulation studies.
a) Physicochemical properties of drugs.
i). pharmaceutical evaluation:-
Bulk density, Tapped density, True density, Angle of repose,
Hausner’s ratio, Carr’s index, etc
ii). Preparation of tablet:-
· Dry granulation/ suitable other method.
· Evaluation parameters:- weight variation, Hardness ,friability,
Dissolution parameters, Swelling index, In vitro study
2. Comparative dissolution studies with marketed formulation.
Comparative dissolution studies with marketed formulation and final formulations will be performed to evaluate the drug release performance.
ENCLOSURE- IV
7.1.SOURCE OF THE DATA:
1) Review of literature from:
a. Journals: such as/
-Indian journal of pharmaceutical sciences. - -International journal of pharmaceutical.
-Biomaterials.
. -Pharmaceutical research.
-European journal of pharmaceutical sciences.
-Drug development and industrial pharmacy.
b. Internet browsing.
c. Standard books
2) Laboratory based studies
3) Library: M.M.U. college of pharmacy
ENCLOSURE- V
7.2 Method of collection of data:
Data on drug collection through literature survey and from physiochemical database. Extensive preformulation trials would provide the basis of section the excipient and system for final formulation development.
ENCLOSURE- VI
7.3 Does the study require any investigation or intervention to be conducted on patients or other? Humans or animals? If so, please mention briefly.
Not applicable
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable.
ENCLOSURE- VII
LIST OF REFERENCES:
1. BommaRamesh, SwamyNaidu, RongalaAppala, Yamsani, Madhusudan Rao;
Devolopment and evalution of Gastro retentive Norfloxacin floating tablets. Acta pharma 29(2009),211-221.
2. Hardman J., Limbard L.. Goodman and Gilman’s The Pharmacological Basis of therapeutics. New Delhi: MacGraw-Hill; 2001,11:1119-1122.
3. Tayade P. Gastroretentive drugs: A review., Express Pharma pulse,2003;14:1-4.
4. Jose GR, Omidian H and shah k. Progress in gastroretentive Drug Delivery systems, Pharmatech,2003,13:152-160.
5. "EMEA Restricts Use of Oral Norfloxacin Drugs in UTIs". UK: DGNews. 24 July2008.
6. Patel VF, Patel NM, Yeole PG. Studies on formulation and evaluation of ranitidine floating tablets. Ind. J Pharm Sci 2005;67(6):703-9.
7. Shrivastava AK, Wadhwa S, Ridhuekar D, Mishra B. Oral sustained delivery of atenolol from floating matrix tablets-formulation and in vitro evaluation. Drug Dev Ind Pharm. 2005;31(4):367-371.
8. Whitehead L, and Collett J.H. Fell J.T., Amoxycillin release from a floating dosage form based on alginates. Int. J. Pharm., 2000,210,45-49.
9. Baumgartnar S., Kristel J, Vreer F, Vodopivec P, Zorco B. Optimization of floating matrix tablets and evaluation of their gastric residence time. Int. J. Pharm., 2000,195(1-2):125-135.
10. Yang L., Eshragi J.and Fassihi R.J. A new intra gastric delivery system for the treatment of Helicobacterpylori associated gastric ulcers: invitro evaluations. J.Control Release., 1999,57(3):215-222.
11. Rahman Z, Mushir A, Khar RK. Design and evaluation of bilayer floating tablets of captopril. Acta Pharm. 2006;56:49–57.
12. Patel VF, Patel NM. Intragastric floating drug delivery system of cefuroxime axetil: In vitro evaluation[Online]. [cited 2006 jul 18];[7 screen]. Available from: URL:http://www.AAPS Pharm Sci Tech
13. Chavanpatil M, Jain P, Chaudhari S, Shear R, Vavia P. Development of sustained release gastroretentive drug delivery system for ofloxacin: In vitro and in vivo evaluation. Int J Pharm.2005;304(1-2):178-84.