FABRICATION AND EVALUATION OF RANITIDINE HYDROCHLORIDE FLOATING TABLETS
M.Pharm. Dissertation Protocol
Submitted to
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA
BANGALORE
BY
D.SANJAY
UNDER THE GUIDENCE OF
Mr.MANJUNATHU.MACHALE
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
C.N.K REDDY COLLEGE OF PHARMACY
BANGALORE-560091
KARNATAKAPDEPARTM
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) / D.SANJAYS/O RAMA RAO.D,
KESANUPALLI(pt), DACHEPALLI(md), GUNTUR(D.T)
A.P pin.no-522414.
2. / NAME OF THE INSTITUTION / C.N.K REDDY COLLEGE OF PHARMACY
MAHADESHWARNAGAR, VISHWANEEDAM POST,BANGALORE-560091.
3. / COURSE OF STUDY AND SUBJECT / M.PHARM,
PHARMACEUTICS
4. / DATE OF ADMISSION OF COURSE / 22-11-2011.
5. / TITLE OF TOPIC / FABRICATION AND EVALUATION OF RANITIDINE HYDROCHLORIDE FLOATING TABLETS
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
6 . / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE- I
6.1 Need for the study
Ranitidine is a histamine H2-receptor antagonist similar to cimetidine and Famotidine. H2 RAs bind competitively to gastric H2 receptors to reversibly inhibit acid secretion. Blockade of perietal cell histamine receptors inhibit all phases of gastric acid secretion induced by histamine, gastrin and acetylcholine. The net effect is an increase in the pH of the stomach.Ranitidine Hydrochloride possessesaHalf life of 2.1 ± 0.2 hr and its bioavailability is 52 ± 11 %. The therapeutic dose is 150-300mg. Hence the present study is to formulate and optimize a controlled release dosage form using GastricFloating 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.
Mechanism of action:
The H2 antagonists are competitive inhibitors of histamine at the perietal cell H2 receptor. They suppress the normal secretion of acid by perietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms histamine released by ECL cells in the stomach is blocked from binding on perietal cell H2 receptors which stimulate acid secretion, and other substances that promote acid secretion(Such as gastrin and acetylcholine) have a reduced effect on perietal cells when the H2 receptors are blocked.10
THERAPEUTIC USES
- The major therapeutic indications are for promoting healing of gastric and duodenal ulcers.
- Treatment of uncomplicated Gastro esophageal Reflux disease (GERD).
- For prophylactic treatment of stress ulcers.
- In addition, it is employed in combination with antibiotics to treat infection with Helicobacter pylori i.e. in the treatment of Gastritis.
The empirical formula is C13H22N4O3S•HCl, representing a molecular weight of 350.87.
Ranitidine HCl is a white to pale yellow, granular substance that is soluble in water. It has a slightly bitter taste and sulphur like odour.
ENCLOSURE- II
6.2 Review of the literature
1.Shahi S.R, Shinde N.V. et al.had developed an optimizedgastric floating drug delivery system. Clarithromycin was used with two formulation variables: X1 (HPMC K4M) and X2 (citric acid). The two formulation variables were found to be significant for the release properties (P < 0.05), while citric acid loading was found to be significant for floating log time1.
2.Shishu, Gupta N. et al.had investigated on single unit floating tablets of 5-FU which, after oral administration,are designed to prolong the gastric residence time, increase drug bioavailability and target the stomach cancer. The optimized formulation could sustain drug release for 24 h and remain Buoyant for 16 h. The mechanism of drug release was predominantly diffusion with a minor contribution from polymeric relaxation. It was Found that the tumor incidence was reduced by 75% using FDDS of 5-FU whereas only a 25% reduced by conventional tablet2.
3.SauzetC, Claeys-BrunoM.et al.had developed an innovative floating gastro retentive dosage form. The developed technology induces a low-density dosage form containing high active pharmaceutical ingredient concentration by using a hydrophobic dusty powder excipients under specific conditions. The new dosage form was obtained by state of the art wet granulation manufacturing process. The GRDF was characterized for apparent density, buoyancy, porosity and dissolution using in vitro experimentations3.
4.Sandra Stubbing, Hendrik Metz et al.had developed Propranolol HCL containing matrix. Tablet floating started immediately and continued for 24h. Furthermore, thenew method of bench top was introduced to study the water diffusion and swelling behaviour non-invasively and continuously4.
5.Srisagul Sungthongjeen, SriamornsakP. et al.had designed floating tablets based on gas formation. The system consists of a drug-containing core tablet coated with a protective layer (HPMC), a gas forming layer (NaHCO3) and a gas-entrapped membrane, respectively. The increased amount of a gas forming agent increased the drug release from the floating tablets while increasing coating level of gas-entrapped membrane increased time to float and retarded drug release5.
6.MallikarjunV, RaviP,et al.had investigated on gastro retentive drug delivery system of Glipizide. It was observed that the tablet remained buoyant for 12-20 hours. The tablets with HPMCK15M were found to float for longer duration as compared with formulations containing HPMCK4 M6.
7.Ramesh Bomma, Rongala Appala Swamy Naidu. et al.had developed Floating matrix tablets of norfloxacin. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets. The best formulation was remained in the stomach for 180 ± 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle7
8.Mahesh Chavanpatil, Para’s Jain,et al. had prolonged the continuous input of the drug to the upper parts of the gastrointestinal (GI) track. Stability of the formulation increases with the increasing psyllium husk concentration. In vitro drug release rate increased with increasing amount of crospovidone due to the increased water uptake. The developed formulation shows promise to be bioequivalent to the marketed product8.
9.StreubelA, SiepmannJ. et al. had developed the Physico chemically characterized single unit, floating controlled drug delivery systems consisting of (i) polypropylene foam powder, (ii) matrix-forming polymer(s), (iii) drug, and (iv) filler. Foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCL at 37.8C. The release rate modified by varying the ‘‘matrix-forming polymer/foam powder’’ ratio, the initial drug loading, the tablet radius and height9.
10.Ramji Anil Kumar Arza et al.worked on drugs with of 5-Fluro uracil narrow absorption window in the gastrointestinal tract which have poor absorption. The drug release follows the Higuchi kinetic model, and the mechanism is found to be non-Fickian. In vivo nature of the tablet at different time intervals is observed in the radiographic pictures of the healthyvolunteers and Mean resident time in the stomach is found to be 320±48.99 min (n=6)10.
11.Havaldar V.D, Kulkarni A.S, Dias R.J. et al.The purpose of the study was to prolong the gastric residence time of atenolol by designing its floating tablets and to study the influence of different polymers on its release rate. The floating matrix tablets of atenolol were prepared by direct compression method. The prepared tablets were evaluated for physicochemical parameters such as hardness, floating properties (floating lag time, floating time and matrix integrity), swelling studies and drug content. All the formulations showed good matrix integrity and retarded the release of drug for eight hours. Diffusion exponent (n) value was found in the range of 0.52-0.99 indicating diffusion as a release mechanism. The swelling studies of all the formulations showed that formulations containing Xanthan gum has higher swelling indices than HPMC K100M and HPMC K4M. It can be concluded that formulations with higher swelling indices retarded the release of drugs more than those with lower swelling indices11.
ENCLOSURE- III
6.3 Objectives of the study
1.Preparation and evaluation of floating tablet of Ranitidine HCl 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 : Ranitidine Hydrochloride.
Polymers : Carbomers,
Carboxymethylcellulose,
HPMC K15M, K4M,
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 excepients, to optimize the formulation.
1.Preformulation studies.
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:-
Hardness,
Friability,
Dissolution parameters,
Swelling index,
In vitro study.
- Comparative dissolution studies with marketed formulation.
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.
- Internet browsing.
- Standard books
3)Library: C.N.K Reddy College of Pharmacy, Bangalore-91.
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.Shahi S, Shinde N.V, Statistical Optimization of Gastric Floating System For Oral Controlled Delivery Of Clarithromycin. Rasayan J.Chem 2008; 1(2): 367-377.
2.Shishu, Gupta N. A, gastro-retentive floating delivery system for 5-fluorouracil. Asian Journal of Pharmaceutical Sciences 2007; 2 (4): 143-149.
3.Sauzet C.Claeys-Bruno M, An innovative floating gastro retentive dosage system: Formulation and in vitro evaluation. International Journal of Pharmaceutics 2009; 378: 23–29.
4.Sandra S, Hendrik M, Characterization of poly (vinyl acetate) based floating matrix tablets. Journal of Controlled Release 2008; 126:149–155.
5.Srisagul S, Pornsak S, Design and evaluation of floating multi-layer coated tablets based on gas formation. European Journal of Pharmaceutics and Biopharmaceutics 2008; 6: 255–263.
6.Mallikarjun V, Ravi , Design and evaluation of Glipizide floating tablets. Journal of Pharmacy Research 2009; 2(4): 691-693.
7.Ramesh B, Rongala A, Swamy N, Development and evaluation of gastro retentive norfloxacin floating tablets. Acta Pharm 2009; 59:211–221.
8.Mahesh C, Para’s Jain, Development of sustained release gastro retentive drug delivery system for Ofloxacin: In vitro and in vivo evaluation. International Journal of Pharmaceutics 2005; 304:178–184
9.Streubel A, Siepmann J, Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release. European Journal of Pharmaceutical Sciences 2003; 18:37–45.
10.Ramji A.K.A, Chandra S, Formulation and Evaluation of Swellable and Floating Gastro retentive Ciprofloxain Hydrochloride Tablets. AAPS Pharm SciTech 2009; 10(1): 220-226.
11.Havaldar V.D, Kulkarni A.S, Dias R.J, Floating matrix tablets of atenolol: Formulation and in vitro evaluation. Asian J Pharm 2009; 3(4):286-291.
12.
13.Desai S Bolton S, “A floating controlled release system: In-vitro in-vivo evaluation” Pharma
Res.1993; 10:1321-5.
14.Muthusamy K, Govindarajan G and Ravi T K, “Preparation and evaluation of Lansoprazole Floating Micropellets”, Ind. J. Pharm. Sci. 2005, 67(1):75-79.
15.Daharwal S J; Gastro retentive drugs: A novel approach towards floating therapy. pharma info.net . 2007; 5(1): 1-20.
16.Bomma R, Veerbrahma K; Development and evaluation of gastroretentive norfloxacin floating tablets. Acta Pharm.2009; 59:211-221.
17. Bomma R, Veerbrahma K; Development and evaluation of gastroretentive norfloxacin floating tablets. Acta Pharm. 2009; 59:211-221.
18.Reddy B A, Rani S B, Vedha hari B N, Punita S; The recent developments on gastric floating drug delivery system: An overview. Int J Pharm Sci Tech. 2010; 2(1): 524-534.
.
19.Yadav S K, Kavita K, Tamizhamani T; Formulation and evaluation of floating tablets of ranitidine hydrochloride using natural and synthetic polymers. Int J pharm Tech Res. 2010; 2(2): 1513-1519..
20.W.Muller, E.Anders, WO Patent 89/06956 1989 Floating system for oral therapy.
9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF GUIDE / FORWARDED FOR APPROVAL
11. / NAME AND DESIGNATION OF
11.1 Guide / Mr. MANJUNATH U. MACHALE
PROFESSOR, DEPT.OF PHARMACEUTICS,
C.N.K REDDY COLLEGE OF PHARMACY,
MADESHWANAGAR, VISHWANEEDAM POST,
BANGALORE-560091, KARNATAKA.
11.2 Signature
11.3 co guide(if any) / Not applicable
11.4 Signature / Not applicable
11.5 Head OF The Department / Mr. MANJUNATH U. MACHALE
PROFESSOR, DEPT.OF PHARMACEUTICS,
C.N.K REDDY COLLEGE OF PHARMACY,
MAHADESHWARNAGAR, VISHWANEEDAM POST, BANGALORE-91,KARNATAKA.
11.6 Signature
12. / 12.1 Remarks Of The Principal / SUBMITTED FOR APPROVAL
12.2 Principal / PROF. SYED ASADULLA, PRINCIPAL, C.N.K REDDY COLLEGE OF PHARMACY, BANGALORE-560091 , KARNATAKA.
12.3 Signature