Rajiv Gandhi University of Health Sciences Karnataka s22

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BANGALORE,

ANNEXURE - II PROFORMA FOR REGISTRATION OF SUBJECTS FOR M.PHARM DISSERTATION

1. Name of the candidate G SRAVAN SRIKANTH And address. R/O THANAKALAN,M:YEDAPALLY, NIZAMABAD,ANDRAPRADESH. RRKS’s College of Pharmacy, 2. Name of Institution Naubad, Bidar-585 402 M. Pharmacy 3. Course of study and subject. (Pharmaceutics) Date of admission to the 4. 5th July 2011 course FORMULATION AND EVALUATION OF 5. Title of Topic ORODISPERSIBLE TABLETS OF METFORMIN HYDROCHLORIDE.

6. BRIEF RESUME OF THE INTENDED WORK: 6.1. Need for the study:

Geriatric patients may have difficulty in swallowing and chewing the tablets resulting in patient non compliance and ineffective therapy. To overcome these problems mouth dissolving tablets are good option. Since, they disintegrate and dissolve rapidly in saliva without need for drinking water1. Orodispersible tablets are those which disintegrate or dissolved in saliva without the need of water. As tablet disintegrates in mouth this could enhance the clinical effect of the drug through pre-gastric absorption from the mouth, pharynx and esophagus. In such cases bioavailability of drug is significantly greater than those observed from conventional dosage form by avoiding first pass metabolism. Many patients express difficulty in swallowing tablets and hard gelatin capsules tending to non compliance and effective therapy. Recent advances in novel drug delivery systems aim to enhance safety and efficacy of the drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance2,3 Metformin hydrochloride is a biguanide antidiabetic. metformin hydrochloride is chemically 1,1-dimethyl-biguanide hydrochloride. It is given by mouth in the treatment of type 2 diabetes mellitus, and is the drug of first choice in obese patient. Initial dosage is 500mg two or three times daily or 850mg once or twice daily with or after meals. Metformin hydrochloride is white crystals,freely soluble in water,slightly soluble in alcohol, practically insoluble in acetone and in dichloromethane.4

The aim of the present investigation is to develop orally disintegrating tablets of Metformin hydrochloride .

1 6.2 Review of literature

 Zade P.S,kawtikwar P.S,sakarkar DM. 5 have studie 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 tablet was prepared with three superdisintegrants e.g. sodium starch glycolate, croscarmellose sodium and crospovidone. Other tablets were prepared by using camphor as sublimating agent. It was concluded that tablets prepared by addition of superdisintegrant has less disintegration time than those prepared by sublimation method.

 Umalkar D.G, et al 6 have studied fast dissolving tablet of Zopicolon were designed with a view to enhance patient compliance. A combination of superdisintegrants i.e. Ac-di-sol (Crosscarmellose sodium), Polyplasdone XL-10, Microcrystalline Cellulose pH 102 was used along with directly compressible dextrose to enhance mouth feel. The prepared batches of tablet were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Also short term stability studies on the formulation indicated that there is no significant change in drug content and in vitro dispersion time.  Abdelbary G.,et al 7.reported that determine the in vitro disintegration profile of rapidly dissolving tablets and correlate with oral disintegration. They evaluated the disintegration profile of RDT manufactured by main commercialized technologies, using texture analyzer. The evaluation of quantitative values as the disintegration onset (t1) and total disintegration time (t2), the characterization of effects of test variables as the disintegration medium and temperature on the disintegration time of RDT and correlation between in vitro and in vivo oral disintegration times. This showed that the use of the texture analyzer in vitro determination of the disintegration behaviors different RDT was shown very successful, convenient and precise.

 Margaret Chandira et al 8. reported a tablet formulation of amlodipine besilate 10 mg tablets developed using direct compression techniques. The dissolution profile of the formulated formulation was compared with the marketed preparation. The results indicated improved dissolution profile of formulation take 30 minutes for complete drug release. To provide the patient with the most conventional mode of administration, there was need to develop ODTs of amlodipine besilatetablet.  Tejash Serasiya et al 9 Studied Orodispersible tablets of pheniramine maleate by direct compression method using various superdisintegrants like Crospovidone, croscarmellose sodium, sodium starch glycolate, low substituted hydroxypropyl cellulose, pregelatinized starch. The prepared tablets were evaluated for uniformity of weight, hardness, friability, wetting time, in-vitro disintegration time, in-vitro dispersion time and drug release study. The concentration of superdisintegrants had an effect on disintegration time and in-vitro drug dissolution whereas hardness and friability of resulting tablets were found to be independent of disintegrant concentration. The two formulations, one containing 10% of Crospovidone and second containing 10% croscarmellose sodium were found to give the best results.

2  Prameela Rani A, Archana N, Sira Teja10 Studied based on dissolution rate the disintegrants can be ranked as Isphagula husk> crosspovidone. Isphagula husk showed better dissolution and dissolution efficiency (DE5%) than the superdisintegrant (Crosspovidone) studied at two levels (4% and 8%). Hence Isphagula husk was recommended as suitable disintegrant for the preparation of directly compressible mouth dissolving tablets of Met.Hcl as these are a very good alternative drug delivery to geriatric and paediatric patients.

 Maniyar N.R, Ranch K.M, Koli AR11 Studied on the basis of the results obtained in the preliminary screening studies, the batch containing Kyron T- 314 showed the fastest disintegration and sodium starch glycollate is widely used in industry, hence, these superdisintegrants were selected for studies. The crushing strength of the tablets was adjusted to 4 kilopond (kp). Subliming agents such as menthol, camphor, and thymol were used to increase porosity of the tablets in thepreliminary tablet formulations. Camphor-containing tablets exhibited faster disintegration as compared with tablets containing menthol and thymol.11 6.3 Objective of the study:

 To develop an Orodispersible tablet of Metformin hydrochloride.

 To carry out compatability studies.

 To evaluate formulation for various quality control parameters

 Stability studies on selected formulatios. .

To permit the arbitrary selection of a batch of tablets with improved dissolution profile and subsequently good bioavailability.

7. MATERIALS AND METHOD 7.1 Source of data:  Internet.  R.G.U.H.S. Library, Bangalore.  International pharmaceutical abstract.

7.2 Materials: Drug: Metformin Hydrochloride Directly Compressible Filler: Microcrystalline cellulose, Mannitol. Sublimating agent: Camphor or Menthol Fast Disintegrant: Croscarmellose Sodium, Crospovidone, Sodium starch glycolate etc. Sweetener: Aspartame Flavorant: Mixed fruit flavor Glidant: Colloidal silicon dioxide Lubricant: Magnesium stearate

7.3 Methods of the preparation of Orodispersible tablets:

3 a) Direct compression: In this method, addition of superdisintegrants in optimum concentration so as to achieve rapid disintegration along with good mouth feels. Superdisintegrants like sodium starch glycollate, crosspovidone, croscarmallose sodium etc; will be used.

b) Sublimation: In this method, mannitol is used as diluent and camphor as a volatile material to prepare highly porous compressed tablets. After compression tablets will be heated in hot air oven at 800 C until a constant weight is obtained to ensure that complete removal of volatilisable component.

c) Use of sugar based excepients: In this method, highly soluble sugar based excepients such as aspartame, dextrose, fructose, etc; are used in order to produce disintegration with good taste masking.

7.4 Evaluation of Mouth dissolving tablets:

Various Orodispersible tablet formulations of Metformin hydrochloride will be formulated and evaluated for hardness, friability, weight variation, disintegration time, drug content, In vitro dissolution rate, short-term stability and drug excepients interaction (IR spectroscopy).

a) Estimation of Drug content: The drug content of Orodispersible tablets will be determined spectrophotometrically at 233 nm.10

b) Disintegration time: Disintegration time of the Orodispersible tablets will be determined by using distilled water at 37±20C as a medium using tablet disintegration test apparatus (USP).

c) In vitro dissolution study: In vitro drug release study of the prepared Orodispersible tablets will be carried in 900ml of 6.8 pH phosphate buffer tablet dissolution tester using paddle stirrer at 50 rpm.10

d) Short term stability: Promising Orodispersible tablets of the drug will be stored at a temperature of 40±20C with 75±5% relative humidity for 1 month and evaluated for drug content, disintegration time and drug-excepients interaction.

7.5 Does the study require any investigation or intervention to be conducted on patients or other humans or animals? (If so please describe briefly)

------Not under the plan of work ------

7.6 Has ethical clearance been obtained from your institution in case of 7.5.

------Not applicable ------

4 8. LIST OF REFERENCES

1) Sudhir Bhardwaj et al, Formulation and evaluation of fast dissolving tablet of aceclofenac. Int. J. Drug Del. 2010; 2: 93-97

2) Raghvendra Rao N. G, Thube Ketan and Suresh D. K.. Formulation and evaluation of mouth dissolving tablet of metoprolol tartrate by sublimation method. Int. J. Pharma. Bio. Sci. ; Vol 1 (2), 2010, 1-14

3) Zhao NA, et al. Functionality Comparison of 3 Classes of Superdisintegrants in Promoting Aspirin Tablet Disintegration and Dissolution, AAPS PharmSciTech.; Vol 6(4), 2005, 634-640.

4) Martindale, The complete drug reference, 34 editions, Page 342.

5) Zade P.S., Kawtikwar P.S., Sakarkar D.M., Formulation, Evaluation and Optimization of Fast dissolving tablet containing Tizanidine Hydrochloride. Int. J. PharmTech. Res.; 1(1), 2009, 34-42

6) Umalkar D.G., Design and Evaluation of Fast Dissolving Tablet of Zopiclone. Int. J. Pharma. Rec. Res.; 2 (2), 2010, 86-91

7) Abdelbary G. et al, Determination of the in vitro disintegration profile of rapidly disintegrating tablets and correlation with oral disintegration. Int. J. Pharm.; 292, 2005, 29–41

8) Margaret Chandira et al, Design, development and optimization of Amlodipine Besylate tablets. Scholars Research Library.; 2 (1), 2010, 528-539

9) Tejash Serasiya, Shailesh koradia, Subhash Vaghani, JivaniI N. P., Design, Optimization and In Vitro Evaluation of Orodispersible Tablets of Pheniramine Maleate. Int. J. Pharma. Res. & Dev.; 1 (10), 2009, 1-18

10) Prameela Rani A. et al, Formulation and Evaluation of orodispersable Metformin tablets: A Comparative study on Isphagula husk and crosspovidone as a superdisintegrants. Int. J. of applied pharmaceutics.,2(3), 2010,15-21.

11) Maniyar N.R. et al, Formulation and optimization of fast disintegrating tablet of Metformin using disintegrant blends for improved efficacy. Pharm sci. monitor an int j of ph. Sci.,2(2), 2011, 1-11.

5 9. Signature of the candidate

10. Remarks of the Guide

11. Name and Designation of (in block letters) 11.1 Guide DATTATREYA B. UDGIRKAR PROFESSOR RRKS COLLEGE OF PHARMACY NAUBAD, BIDAR. 11.2 Signature

12. Name and Designation (In block letters) NOT APPLICABLE

12.1 Co – Guide ------

------12.2 Signature 13. 13.1 Remarks of the Chairman and Principal.

13.2 Signature

( Dr. K SREENIVASA RAO )