FORMULATION AND EVALUATION OF RAPIDLY DISINTEGRATING ORAL TABLETS OF FAMOTIDINE
M. Pharm. Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore – 560041
By
Mr. LOKESH SIDRAM SAJJANSHETTE B.Pharm
Under the Guidance of
Prof. S.P. THAKKER M.Pharm
DEPT. OF PHARMACEUTICS
Department of Pharmaceutics
SET’s College of Pharmacy, S. R. Nagar,
Dharwad, Karnataka – 580002.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE
KARNATAKA
ANNEXURE-II
PROFORMA OF REGISTRATION OF SUBJECT OF DISSERTATION
1. / NAME OF THE CANDIDATEAND ADDRESS / Mr. LOKESH SIDRAM SAJJANSHETTE
DEPARTMENT OF PHARMACEUTICS
SET’s COLLEGE OF PHARMACY,
S. R. NAGAR, DHARWAD -580002.
2. / NAME OF THE INSTITUTION / SET’s COLLEGE OF PHARMACY, S.R. NAGAR DHARWAD- 580002.
3. / COURSE OF THE STUDY AND SUBJECT / MASTER OF PHARMACY IN
PHARMACEUTICS
4. / DATE OF ADMISSION TO THE COURSE / JUNE-2010
5. / TITLE OF THE TOPIC:
FORMULATION AND EVALUATION OF RAPIDLY DISINTEGRATING ORAL TABLETS OF FAMOTIDINE
6.
7.
8. /
BRIEF RESUME OF THE STUDY
6.1 NEED FOR THE STUDY:Oral dosage forms like tablets and capsules possess great problem of swallowing mainly for pediatrics, geriatrics, and bedridden, nauseous or non-compliant patients’. Orally disintegrating dosage form has to be placed in mouth and then it will get dispersed in saliva without the need of water. Orally disintegrating tablets are also called as orodispersible, mouth dissolving, rapidly disintegrating, fast melt, and quick dissolve system. From past decade, there has been an increased demand for more patient-friendly and compliant dosage forms. As a result, the demand for developing new technologies has been increasing day by day. United States Food and Drug Administration (FDA) define orally disintegrating tablets as “A solid dosage form which contain a medicinal substance or active ingredient which disintegrates rapidly within a matter of seconds when placed upon a tongue”. US Food and Drug Administration Center for Drug Evaluation and Research (CDER) defines, in the ‘Orange Book’, an oral disintegrating tablet as “a solid dosage form containing medicinal substances, which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue.”1
Famotidine is categorized under H2 receptor antagonist. The H2 receptor antagonist inhibits acid production by reversibly competing with histamine for binding to H2 receptor on the basolateral membrane of parietal cells. The bioavailability of the drug is about 20-66 % and protein binding is about 15-22 % in plasma. It bypasses the first pass hepatic metabolism. The elimination half life of the drug is about 3.3 hr. The dose of the drug is 20-40 mg once or twice a day.
The bioavailability and plasma protein binding of famotidine is less. The aim of the present work is to formulate oral disintegrating tablets for the improvement of pharmacological action.
6.2 REVIEW OF LITERATURE:
Rangole US et.al; formulated fast disintegrating tablets of hydrochlorothiazide using different concentrations (2%, 3%, 4% and 5%) of superdisintegrants like croscarmellose sodium and crospovidone. crospovidone in the concentration of 4% gives fast disintegration in 16 sec and showed 100% drug release within 14 min.2
Sawarikar PP et.al; studied development and evaluation of inclusion complex of isoxsuprine hydrochloride with β-cyclodextrin using kneading and coprecipitation methods. Fast dissolving or disintegrating tablets composition with 20 mg equivalent isoxsuprine HCl were prepared using superdisintegrants like sodium starch glycolate, ac-di-sol and crospovidone by direct compression method. The tablets were disintegrated within 8 to 20 sec and almost 100% of drug released from all formulations within 10 min. The formulation consisting of 5% ac-di-sol showed complete release of drug within 4 min.3
Gudas GK et.al; studied preparation of fast dissolving tablets of Chlorpromazine HCl in the oral cavity with enhanced dissolution rate. The tablets were prepared with five diffrent superdisintegrants e.g. sodium starch glycolate, crospovidone, croscarmellose, L-hydroxypropyl cellulose (L-HPC), pregelatinized starch. It was concluded that the fast dissolving tablets with proper hardness and rapid disintegration time can be made using selected superdisintegrants.4
Rampure MV et.al; studied formulation of fast dissolving phenobarbitone tablets by direct compression method with a view to enhance patient compliance. The work was carried out by using three different superdisintegrants (2-8% w/w) i.e., L-hydroxypropyl cellulose (L-HPC), pregelatinized starch, crospovidone with varying concentration of microcrystalline cellulose (5-15% w/w) and directly compressible mannitol (Pearlitol SD 200) used as a diluent to enhance the mouth feel. Among the promising formulations, the formulations containing 8% w/w of crospovidone and 15% w/w of microcrystalline cellulose emerged as the overall best formulation based on the in vitro drug release compared to conventional commercial tablet.5
Zade PS et.al; prepared bitterless fast dissolving tablet of tizanidine hydrochloride using eudragit E 100 as a taste masking agent. Mass extrusion was the technique used for preparing taste masked granules. The tablets were prepared with three diffrent superdisintegrants e.g. sodium starch glycolate, croscarmellose sodium and crospovidone. Disintegration in oral cavity was tested and found to be 22 sec. Other tablets were prepared by using sublimating agent. It was concluded that tablets prepared by addition of superdisintegrants has less disintegration time than those prepared by sublimation method.6
Sheth SK et.al; developed a taste masked oral disintegrating tablet of poorly soluble lornoxicam by direct compression technique with β-cyclodextrin (BCD) complexes using various superdisintegrants like sodium starch glycolate, crospovidone and croscarmellose sodium. The different formulations showed disintegration time between 22 to 58 sec. Drug release times were ranged between 8 to 20 min. Among all the formulations, formulation containing β-cyclodextrin (BCD) 11.23 mg, croscarmellose sodium 15 mg showed 99.85 % drug release within 8 min. Thus, it was considered best among the other formulations.7
Prajapati BG et.al; formulated directly compressible orally disintegrating tablets of piroxicam with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age group for easy administration. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied. Release of drug was quick from formulations containing 7% crospovidone compared to the other orally disintegrating tablets prepared.8
Gandhi PP et.al; studied the effect of different resins as a superdisintegrants and comparison of their superdisintegrants action. Orodispersible tablets of metformin hydrochloride were prepared by using Indio294, Tulsion349, Doshion, Amberlite388 as superdisintegrants by direct compression. All the formulations showed low weight variation with dispersion time less than 30 sec and rapid in vitro dissolution. The results revealed that the tablets containing superdisintegrants had a good dissolution profile.9
6.3 OBJECTIVE OF THE STUDY:
· To carry out compatibility studies.
· To develop oral disintegrating tablets of famotidine.
· To evaluate formulations for various quality control parameters.
METHOD OF COLLECTION OF DATA
7.1 SOURCE OF DATA:
· Reference books.
· www.Helinet.in.
· International journal of drug delivery.
· International journal of pharm tech research.
· International journal of pharm and bio sciences.
· Research journal of pharm and technology.
· Journal of chemical and pharmaceutical research.
· Journal of current pharmaceutical research.
7.2 MATERIALS AND METHODS:
MATERIAL:
· Famotidine.
· Various superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, etc will be used.
· Tablet additives.
METHOD:
The active agent and excipients will be formulated into tablets by suitable method.
EVALUATION STUDIES:
1. Precompression studies.
Ø Bulk density
Ø Tapped density
Ø Angle of repose
Ø Hausner’s ratio
Ø Carr’s index
2. Post compression studies.
Ø Thickness
Ø Hardness
Ø Friability
Ø Weight variation
Ø Water absorption ratio
Ø Wetting time
Ø Drug content
Ø In-vitro disintegrating time
IN-VITRO DISSOLUTION STUDY:
In-vitro dissolution study will be carried out using USP XXIII dissolution test apparatus with suitable dissolution medium. A 900 ml of the dissolution fluid is used at 37±0.50C with stirring speed of 50 RPM. Samples are withdrawn at 2, 4, 6, 8 and 10 minutes time interval by replacing with same volume of the dissolution medium. Samples are then analyzed by measuring the absorbance at 265 nm using UV spectrophotometer.4
7.3 DOES THIS STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.
- No.
7.4 ETHICAL CLEARANCE:
- Not applicable.
LIST OF REFERENCES:
1) Wagh MA, Kothawade PD, Salunkhe KS, Chavan NV, Daga VR. Techniques used in orally disintegrating drug delivery system. Int J Drug Deliv 2010;2:98-107.
2) Rangole US, Kawtikwar PS, Sakarkar DM. Formulation and in-vitro evaluation of rapidly disintegrating tablets using hydrochlorothiazide as a model drug. Res J Pharm Tech 2008 Oct-Dec;1(4):349-52.
3) Sawarikar PP, Sridhar BK, Shivkumar S. Formulation and evaluation of fast dissolving/ disintegrating tablets of isoxsuprine hydrochloride. J Cur Pharm Res 2010;3(1):41-6.
4) Gudas GK, Manasa B, Rajesham VV, Kumar SK, Kumari JP. Formulation and evaluation of fast dissolving tablets of chlorpromazine HCl. J Pharm Sci Technol 2010;2(1):99-102.
5) Rampure MV, Bendegumble B, Raju SA, Deshpande R, Swamy PV. Formulation design of rapidly disintegrating phenobarbitone tablets by direct compression method. Int J Pharm Bio Sci 2010 Oct-Dec;1(4):62-8.
6) Zade PS, Kawtikwar PS, Sakarkar DM. Formulation, evaluation and optimization of fast dissolving tablet containing tizanidine hydrochloride. Int J Pharm Tech Res 2009 Jan-March;1(1):34-42.
7) Sheth SK, Patel SJ, Shukla JB. Formulation and evaluation of taste masked oral disintegrating tablet of Lornoxicam. Int J of Pharm Bio Sci 2010;1(2):1-9.
8) Prajapati BG, Patel B. Formulation, Evaluation and optimization of orally disintegrating tablet of piroxicam. Int J Pharm Tech Res 2010 July-Sept; 2(3):1893-9.
9) Gandhi PP, Vaidya KA, Shelake GT, Yadav JD, Kulkarni PR. Formulation and evaluation of metformin hydrochloride fast disintegrating tablets by using polacrilin potassium NF from different sources as superdisintegrants. Int J Pharm Pharm Sci 2010;2(2):55-7.
9. / SIGNATURE OF THE STUDENT
10. / REMARK OF THE GUIDE
The above mentioned information and literature has been extensively investigated, verified and was found to be correct. The present study will be carried out under my supervision and guidance.
11. / 11.1 NAME AND DESIGNATION
OF THE GUIDE
11.2 SIGNATURE / PROF. S.P. THAKKER M. Pharm,
DEPARTMENT OF PHARMACEUTICS,
SET’S COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580002.
11.3 NAME AND DESIGNATION
OF CO-GUIDE
11.4 SIGNATURE / ------
11.5 HEAD OF THE
DEPARTMENT
11.6 SIGNATURE / PROF. S.P. THAKKER M. Pharm,
DEPARTMENT OF PHARMACEUTICS,
PROFESSOR AND HEAD,
SET’S COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD- 580 002.
12. / 12.1 REMARK OF THE
PRINCIPAL
12.2 SIGNATURE / The above mentioned information is correct and I recommend the same for approval.
Dr. V.H. Kulkarni M. Pharm, Ph.D.,
PROFESSOR & PRINCIPAL,
SET’s College of Pharmacy,
S.R.NAGAR, DHARWAD- 580 002.
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