FORMULATION AND IN VITRO EVALUATION OF GRANISETRON HYDROCHLORIDE FAST DISINTEGRATING TABLETS
M. Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore.
By
DANAKKA SPANDANA
B.Pharm.
Under the Guidance of
Dr. JAGADEESH G. HIREMATH
Asst. Professor
DEPARTMENT OF PHARMACEUTICS
N.E.T. PHARMACY COLLEGE
RAICHUR.
2009
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of candidate and address (In Block Letters) / DANAKKA SPANDANAD/O DANAKKA NARSAIAH,
H.NO.23-8/3.MILINIUM TOWN SHIP, LINGAREDDY GUDA ROAD, SHADNAGER, MAHABUBNAGER DISTRICT.AP.PIN 509216
2 / Name of the Institute / N.E.T.PHARMACY COLLEGE, RAICHUR.
3 / Course of study and subject: / M.PHARM. PHARMACEUTICS.
4 / Date of admission of course: / 23-05-2009
5 / Title of the topic:
“FORMULATION AND IN VITRO EVALUATION OF GRANISETRON HYDROCHLORIDE FAST DISINTEGRATING TABLET”
6 / Brief Resume of this intended work:
6.1 Need for the study Enclosure-I
6.2 Review of Literature Enclosure-II
6.3 Objectives of study Enclosure-III
7 / Materials and Methods:
7.1 Source of data Enclosure-IV
7.2 Method of collection of data (Including sampling procedure, if any)
Enclosure-V
7.3 Does the study require any investigation or interventions to be conducted on patients of humans or animals? If so, please describe briefly.
------NO------
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
------NOT APPLICABLE------
8 / List of References Enclosure-VI
9 / Signature of the candidate
10 / Remarks of the Guide / The proposed work can be carried out in the laboratory.
11 / Name and designation of (in block letters)
11.1 Guide
11.2 Signature /
Dr. JAGADEESH G. HIREMATH
Asst. Professor
Dept. of Pharmaceutics
N.E.T. Pharmacy College,
Raichur-584 103.
11.3 Co-Guide (if any)
11.4 Signature / ------
------
11.5 Head of Department
11.6 Signature /
Dr. H DODDAYYA
Professor
Dept. of pharmaceutics
N.E.T. Pharmacy college,
RAICHUR- 584 103.
12 / 12.1 Remarks of the Chairman and Principal
12.2 Signature / Dr. H. DODDAYYA
Principal
N. E. T. Pharmacy College,
RAICHUR-584 103.
Enclosure-I
6) Brief resume of the intended work:
6.1) Need for the study:
The oral route of administration still continues to be the most preferred route due to its manifold advantages including ease of ingestion, pain avoidance, versatility and most importantly patient compliance1. Oral solid dosage forms are popular because of ease of administration, accurate dosage, self medication, pain avoidance and most importantly patient compliance2. Among the pharmaceutical dosage forms, the conventional tablet seems to be most popular, because of its ease of transportability and comparatively lower manufacturing cost3.
There are several factors other than physicochemical properties of the drug that may influence the dissolution rate, bioavailability of drugs from the solid dosage forms. It has been shown that, the dissolution rate of pure drugs can be altered significantly by the proper selection of formulation components as well as processing methods4. Reports related to effect of formulation excipient like diluents5, disintegrants6, surfactants7, granulating agents and binders are available8, 9.
Granisetron hydrochloride is soluble in water, sparingly soluble in methyl chloride and slightly soluble in methanol having half life about 6-8 hrs, protein binding 65%, bioavailability 60% and dose 1 mg twice a daily and 2 mg once daily10. Granisetron hydrochloride is serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting centre in medulla oblongata. Granisetron hydrochloride is also available in the form of multi dose vials but the drawback associated with this formulation is headache, constipation, weakness, sleepness, diarrhea or abdominal pain, anemia. Few articles are available on fast dissolving tablet of granisetron hydrochloride.
Cardinal Health was the first company to develop and market a fast disintegrating, freeze-dried porous wafer known as Zydis (Seager, 1998; Katou et al., 1993). CIMA also marketed an effervescent tablet known as Orasolve (Wehling et al., 1991). Others include Eisai and Ethypharm, who developed the EMP tablet (Tushima, 2001) and Flashtab (Cousin et al., 1995), respectively. However, some of these technologies have disadvantages i.e. new equipment, such as freeze-driers and specially molded tableting machines, were required for their production. Furthermore, these formulations were difficult for the aged to handle because of inadequate strength.
The objectives of the study is to prepare granisetron hydrochloride containing fast disintegrating tablets(FDT), by using natural/synthetic super disintegrnants alone or their combinations for the preparation of FDT, to achieve sufficient hardness for handling/disintegrate rapidly and can be manufactured by direct compression method to improve patient compliance.
Enclosure-II
6.2) Review of literature:
1) Kumar ND et al., prepared the fast dissolving tablet of granisetron hydrochloride using low and high compressible saccharides along with super disintegrnants like crospovidone, croscarmellose sodium and Low- hydroxyl propyl cellulose. They found that the prepared tablets showed in vitro dispersion with improved mouth feel with good robustness of the tablet. The prepared tablets were found with drug content in the range of 98.42- 99.37%, hardness in the range of 2.86-3.86 kg/cm2 and friability below 1% indicates good mechanical resistance of the tablets. Among prepared formulations by varying the concentration of three superdisintegrant tablets prepared with crospovidone (8%w/w), crosscarmalose sodium (8%w/w), and low-hydroxyl propyl cellulose (8%w/w), were found to be promising and displayed an in vitro dispersion time ranging from 12-23 second which facilitates their faster dispersion in mouth11.
2) Sreenivas et al., formulated ondansetron HCl mouth disintegrating tablets by direct compression method by taking various disintegrnants like crospovidone, croscarmellose sodium, pregelatinized starch, sodium starch glycolate and L-hydroxypropyl cellulose. Results suggested that rapid disintegration was observed with crospovidone and croscarmellose sodium due to the rapid uptake of water and swelling effect. In conclusion 10% w/w disintegrant concentration was suitable for the preparation of ondansetron HCl with croscarmellose sodium and crospovidone respectively12.
3) Sharma S et al., developed the FDT of promethazine theoclate by direct compression method by using different superdisintegrants Ac-Di-Sol, sodium starch glycolate (SSG) and crospovidone in different concentrations. Tablets containing Ac-Di-Sol showed faster disintegration time 52.17 sec. with in vitro release of 72.57% in 5 min compared to tablets from other formulations13.
4) Singh SK et al., prepared fast disintegrating tablets of omeprazole and domperidone combination using pertinent disintegrant (kollidon CL, Ac-Di-Sol and SSG) using mannitol as diluents and sodium saccharin as sweetening agent by direct compression method. Omeprazole and domperidone were well resolved and retention times were around 9.01 and 6.2 respectively. Their obtained results suggested that, the tablet formulation prepared with 4.76% Ac-Di-Sol i.e. 10 mg showed disintegration time of 15 seconds in vitro. Hardness friability, dissolution time and assay of prepared tablets were found to be acceptable according to standard limits14.
5) Jha SK et al., formulated the novel melt-in-mouth tablets of haloperidol by incorporating different superdisintegrants, croscarmellose sodium, sodium starch glycolate and crospovidone by direct compression method. Among all formulations tablets containing 16% w/w of crospovidone disintegrate faster (24.62±0.04 sec) compared to other tablets from different formulation with 98.32±0.02% of drug release in 12 min with hardness, friability and drug content within the specifications15.
6) Zade PS et al., developed the tizanidine HCl fast disintegrating tablet using different superdisintegrants, e.g. sodium starch glycolate, croscarmellose sodium and crospovidone. The blend was examined for angle of repose, bulk density, tapped density and hausner’s ratio as well as hardness, drug content and friability disintegration and dissolution time which found within the limits. Among all the formulation, tablets prepared with crospovidone (57%w/w) as less disintegration time of 10.33 sec and drug release was found to be 100.57% within 20 min. While the tablets prepared with camphor (30%) disintegrated faster in 1.31 min16.
7) Shirsand SB et al., prepared fast dissolving of clonazepam with three superdisintegrants viz., crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios by direct compression method and microcrystalline cellulose used as directly compressible vehicle, mannitol (Pearlitol SD 200) to enhance mouth feel. Among the three promising formulations, the formulation prepared by using 10%w/w of crospovidone and 35%w/w of microcrystalline cellulose emerged as the overall best formulation (t50% 1.8 min) based on the in vitro drug release characteristic compare to conventional tablet formulation (t50% 16.5 min )17.
8) Patel DM et al., formulated the etorocoxib granules containing menthol, ammonium bicarbonate, camphor as subliming agents with crospovidone, aspartame and mannitol by wet granulation technique. Menthol was sublimed from the granules by exposing the granules to vacuum then compressed into tablets. The tablets were evaluated for percentage friability and disintegration time. The tablets prepared with mannitol (10%w/w) showed least disintegration time and concentration dependent disintegration was observed in the tablets prepared with camphor as a subliming agent18.
9) Rangasamy M et al., developed fast dissolving tablets of terbutaline sulfate by the direct compression method by incorporating superdisintegrants such as Explotab, Ac-Di-Sol and polyplasdone XL in different concentrations. The prepared tablets were evaluated for weight variation, thickness, and hardness, friability, wetting time, drug content, water absorption ratio, in vitro disintegration time and in vitro drug release. Tablets prepared with different concentration of superdisintegrants hardness, thickness and friability were observed in specified limits. Among all formulation tablets prepared with 5% w/w polyplasdone XL were considered best with 99.33% of in vitro drug release in 10 min19.
10) Amin P et al., prepared mouth dissolving tablets with different concentrations of superdisintegrants in different ratios with three different drugs, after evaluation of tablet the result was found that tablets containing drug: Indion 204 complex were found with good dispersion time 99-101.09 sec and in vitro drug release was found to be 87.26-95.49% in 30 min which indicates good disintegrating property of Indion-204 compared with sodium starch glycolate, crospovidone and crosscarmalose sodium20.
Enclosure-III
6.3) Objective of the study:
The present study is planned with the following objectives:
- To develop FDT formulation for granisetron hydrochloride by using different super disintegrnants and technologies.
- To evaluate pre and postcompressional parameters.
- To characterize the drug-excipient interaction.
- To evaluate the formulations for various physicochemical parameters.
- To carry out the in vitro release studies.
- To carry out stability studies as per ICH guidelines
Enclosure-IV
7) Materials and Methods:
7.1) Source of data:
Primary data: This data will be collected by conducting laboratory experiments and recording the observation.
Secondary data: This will be collected from various journals and textbooks.
Enclosure-V
7.2) Method of collection of data:
The data for the study is planned to collect from the laboratory based experiments, which include the following
- Preparation of newer fast disintegrating tablet formulations of granisetron hydrochloride using different super disintegrnants like crospovidone, sodium starch glycolate, Indion 214, croscarmellose adopting different methods like direct compression, wet granulation etc.
- Evaluation of precompressional parameters such as bulk density, tapped density, angle of repose, Carr’s index, Hausner’s ratio by adopting reported/official methods.
- Evaluation of postcompressional parameters such as hardness, friability, weight variation, drug content, wetting and disintegration time by using reported/official methods.
4. Evaluation the physicochemical characterization of drug and excipients by Furiour Transformer infra-red spectroscopy, Differential Scanning Colorimetry and X-ray diffraction.
- The selected formulation will be subjected for stability studies using stability chamber as per ICH guidelines.
Enclosure- VI
8) List of references:
1. Kuchekar BS, Bhise SB, Arumugam V. Design of fast dissolving tables. Ind J Pharm Edu 2001; 35(4): 150-52.
2. Chien YW. Novel drug delivery systems. 2nd Ed. New York: Marcel Dekker; 1992.
3. Reddy LH, Ghosh B, Rajneesh. Fast dissolving drug delivery systems: A review of the literature. Indian J Pharm Sci 2002; 64(4): 331-36.
4. Abdou HM. (Ed). Factors affecting the rate of dissolution of solid dosage forms. In; Dissolution, bioavailability and bioequivalence. Mack publishing company eastonpennsvivanio: 73-105.
5. Albertini B, Cavallari C, Passerini N. Evaluation of beta- lactose, PVP K12 and PVP K90 as excipients to prepare piroxicam granules using two wet granulation techniques. Eur J Pharm Biopharm 2003; 56: 479-87.
6. Solvang S, Finhold P. Phenobarbital tablets by wet and dry granulation methods. J Pharm Acta Helv 1970; 59: 49-56.
7. Chen LR, Wesley JA, Bhattachar S, Ruiz B, Bahash K, Babu SR. Dissolution behaviour of a poorly water soluble compound in the presence of tween 80. Pharm Res 2003; 20(5): 797-801.
8. Marlowe E, Shagraw R. Sodium salicylate tablet using wet granulation and direct compression methods. Indian J Pharm Sci 1967; 56: 498-503.
9. Chebli C, Cartilier L. Cross linked cellulose as a tablet excipient: A binding/disintegrating agent. Indian J Pharm 1998; 171: 101-10.
10. Drug Information AHFS: American Society of Health-System Pharmacists® 2004.
11. Kumar ND, Raju SA, Shrisand SB, Para MS. Formulation design of novel fast dissolving tablets using low and high compressible saccharides. IJPRIF 2009; 1(4): 1585-88.
12. Sreenivas SA, Gadad AP, Dandagi PM, Mastiholimath VS, Patil MB. Formulation and evaluation of ondansetron hydrochloride directly compressed mouth disintegrating tablets. Indian Drugs 2005; 43 (1): 35-38.
13. Sharma S, Gupta DG. Formulation and characterization of fast-dissolving tablet of promethazine theoclate. Asian Journal of Pharmaceutics 2008: 70-72.
14. Singh SK, Mishra DN, Jassal R, Soni P. Fast disintegrating combination tablets of omeprazole and domperidone. Asian Journal of Pharmaceutical and Clinical research 2009; 2(4): 54-62.
15. Jha SK, Vijayalaxmi P, Karki R, and Goli D. Formulation and evaluation of melt-in-mouth tablets of haloperidol. Asian Journal of Pharmaceutics 2008: 255-60.
16. Zade SP, Kawtikwar SP, Sakarkar MD. Formulation, evaluation and optimization of fast dissolving tablets containing tizanidine hydrochloride. Int J Pharm Tech Res 2009; 1(1): 35-42.
17. Shirsand SB, Suresh S, Swamy PV, Kumar ND and Rampure MV. Design and evaluation of fast dissolving tablets of clonazepam. Indian J Pharm Sci 2008; 70(8): 791-95.
18. Patel MD, Patel MM. Optimization of fast dissolving etorocoxib tablets prepared by sublimation technique. Indian J Pharm Sci 2008; 70(1): 71-76.
19. Rangasamy M, Ayyasamy B, Raju S, Gummadevelly S. Design and evaluation of the fast dissolving tablet of terbutaline sulfate. Asian Journal of Pharmaceutics 2009: 215-17.
20. Amin P, Prabhu N, and Wadhwani A. Indion 414 as superdisintegrant in formulation of mouth dissolve tablets. Indian J Pharm Sci 2009; 71(2): 116-19.
3