Impact factor: 3.958/ICV: 4.10 ISSN:

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1 Impact factor: 3.958/ICV: 4.10 ISSN: Pharma Science Monitor 8(1), Jan-Mar 2017 PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES Journal home page: FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE SUSTAINED RELEASE TABLETS M.D.Seema Farheen* 1 Saidulu Sappori 2, Mangulal. Kethavath 3, G.Kalpana 4 1Department of Pharmaceutics, Nizam college of pharmacy, Piglipur (V), R.R(Dist) , Telangana, India. 2Department of Pharmacology, Slc s college of pharmacy, Piglipur (V), R.R(Dist) , Telangana, India. 3Department of Pharmaceutics, Slc s college of pharmacy, Piglipur (V), R.R(Dist) , Telangana, India. 4Department of Pharmaceutical Analysis, Slc s college of pharmacy, Piglipur (V), R.R(Dist) , Telangana, India. ABSTRACT An attempt was to formulate the oral sustained release Metformin hydrochloride matrix tablets by using hydroxyl methyl cellulose polymer (HPMC) as rate controlling factor and to evaluate drug release parameters as per various release kinetic models. It is observed that the basic goal of therapy in the development of Metformin hydrochloride release dosage form is to increase bioavailability; reduce risk of hospitalization, deliver drug at a near constant rate for approximately 12 hrs, independent of food intact and gastrointestinal ph. Method. The dry granulation technique was used to compress the tablet as powder showed the poor flowability; less cohesiveness during direct compression and due to moisture sensitivity and tendency to hydrolyte, wet granulation techniques was not selected for the present work. Dry granulation improves the flow of the powder and reduces the use of excipient.the granules were evaluated for angle of repose, loose bulk density, tapped density, compressibility index, total porosity, drug content, etc and showed satisfactory results. The in-vitro dissolution study was carried out for 12 hours using ph 4.0, 6.8 phosphate buffer in phosphate buffer as dissolution media. All the tablet formulations showed acceptable pharmacotechnical properties and compiled with pharmacopoeial specifications. The mechanism of drug release form matrix tablet is governed by diffusion and as the drug is so highly soluble. KEYWORDS: HPMC, Metformin Hydrochloride, Sustained release, phosphate buffer, Dry granulation. INTRODUCTION Diabetes is one of the major causes of death and disability in the world. Metformin HCl (MTH) is an anti-diabetic agent which is prescribed for the treatment of non-insulin dependent diabetes mellitus. In present investigation the matrix tablet dosage form of MTH was prepared by taking an advantage of naturally occurring LBG and extensively used synthetic polymer, HPMC K15, for sustained release of the drug. The study involves preparation of matrix tablet by non-aqueous granulation method using various combinations of the polymers and evaluation of prepared tablets for their physicochemical properties. Sustained release delivery systems have added

2 Impact factor: 3.958/ICV: 4.10 ISSN: advantages over immediate release dosage form. These include reduction of dosing frequency by administering the drug once or twice a day (1, 2). MATERIALS AND METHODS Metformin Hydrochloride was obtained as gift sample from Aurabindo Pharma Ltd., Hyderabad. HPMC-K100 and HPMC-K15 was obtained as gift sample from KMV Enterprises, Hyderabad. Fumed silica and Magnesium stearate was procured from Signet Chemical Corporation, Mumbai Formulation development of metformin sustained release tablets. Table 1. Formula design of metformin sustained release tablets S.No Ingredient F-1 F-2 F-3 F-4 F-5 F-6 1 Metformin Hydrochloride HPMC-K HPMC-K Microcrystalline cellulose Fumed silica Magnesium stearate Procedure for dry granulation Sifting Sifted the following ingredient through 30 meshes in the following order in a vessel, Metformin hydrochloride, Hydroxy propyl methyl cellulose (HPMC) methocel K 100 M Premium USP/BP, hydroxyl propyl methyl cellulose (HPMC) methocel K -4M premium USP/BP, Microcrystalline cellulose, are was taken in case of fluffy materials. Mixing All the sifted ingredients were mixed thoroughly; not less than 5 minutes and until to get the uniform mixed powder.

3 Impact factor: 3.958/ICV: 4.10 ISSN: Lubrication Sifted colloidal silicon dioxide (Aerosil) 50% through the 30 meshes and mixed with that blended powder, sifted magnesium stearate 50% through the 30 meshes and mix with that blended powder. Slugging Above blended powder was then slugged by tablet punching machine, keeping moderate hardness to get granules. Milling These slugged tablets were then milled and passed through 20 meshes. Final lubrication Sifted remaining aerosil through 30meshes and mixed well with that milled granules. Sifted magnesium stearate remaining portion through 30 meshes and mixed thoroughly with these granules [52]. Compression Compressed the above granules with the help of 20 X 9 mm punch size (4, 5, 6 ). Evaluation of sustained release tablets Physical appearance The tablets were inspected for smoothness, absence of cracks, chips and other undesirable characteristics. Weight variation test 20 tablets were randomly selected from each formulation and their average weight was calculated using digital balance. Hardness The hardness test is performed to measure the tablet strength. Tablet should be hard enough to withstand packing and shipping ( 7,8,9, 10 ) Thickness Thickness was determined for 20 pre weighed tablets of each batch using a digital vernier scale and the average thickness was determined in mm. Percentage Friability The friability test gives an indication of tablets ability to resist chipping and abrasion on handling during packaging and shipping. Usually for conventional tablets friability value of 1.0% or less is desirable.

4 Impact factor: 3.958/ICV: 4.10 ISSN: Dissolution study (By UV method) The dissolution test measures the rate of release of the drug from the dosage form in vitro, it is usually expressed as extent of dissolution (% drug content) occurring after a given time under specified conditions. For effective absorption of oral solid dosage form, simple disintegration of the dosage form is not adequate and the dissolution of the drug into the surrounding medium plays a vital role (11, 12, 13 14) RESULTS Pre- formulation parameters Table 2. Pre-compression parameters for formulations F-1 to F-6 Formula Angle of Compressibility LOD Hausner ratio repose Index (%) (%) F ± ± ± ±0.4 F ± ± ± ±0.2 F ± ± ± ±0.2 F ± ± ± ±0.3 F ± ± ± ±0.3 F ± ± ± ±0.3 LOD-Loss on drying In-process evaluation parameters Table 3. Post compression parameters for formulations F-1 to F-6 Avg.weight Thickness Hardness Formula (mg) (mm) (kp) Friability (%) F ± ± ± ±0.4 F ± ± ± ±0.4 F ± ± ± ±0.3 F ± ± ± ±0.5 F ± ± ± ±0.6 F ± ± ± ±0.4

5 Impact factor: 3.958/ICV: 4.10 ISSN: In vitro dissolution profile Table 4. Cumulative percentage release of different formulation Sampling Time (hrs) Cumulative Percentage Drug Release F-1 F-2 F-3 F-4 F-5 F ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± Cumilative percentage of drug release Cumulative percentage of drug release F-6, 76.8 F-5, 67.3 F-4, 57.3 F-3, 48.8 F-2, 39.9 F-1, 34.2 F-1 F-2 F-3 F-4 F-5 F-6 Hours Figure : 1 Comparison of percentage of drug release of different formulations

6 Impact factor: 3.958/ICV: 4.10 ISSN: DISCUSSION In present work attempts have been made to formulate sustained release matrix tablets of Metformin hydrochloride by using polymer, which is preferably used as an anti-diabetic and in case of type-2 diabetic mellitus. Matrix tablets prepared using polymer with HPMC-K100, in different concentration by Dry granulation technique. Metformin hydrochloride meets all the ideal characteristics to formulate as matrix type sustained release drug delivery system. Under preformulation study, the organoleptic properties were complies with the USP specifications. Physical properties such as bulk density and tapped density were more in case of granules ready for compression than that of Metformin raw powder. Melting point determinations were given the information about distribution purity of the drug powder respectively. Loss on drying was with in the USP limit and the result of angle of repose of drug powder showed poor flow properties, slugging of powder with other excipients were done to improve its flow as well as to increase the bulk and true density. The physical compatibility evaluation was performed in visual basic. The study complies with other, as there was no change of physical description. All formations were evaluated on the basis of pharmacopoeial specification. Hardness, thickness, weight variation, dissolution were carried out for all cases. Selected formulation was compared with the marketed product in same strength. Selected formulation (F -1) of 500 mg showed as same as drug release (15, 16, 17, 18) CONCLUSION In present study the attempts were made to formulate 500mg sustained release once day formulations, which can provide effective drug release for 12 hours. Sustained release matrix tablets Metformin hydrochloride, were prepared by dry granulation. In vitro study showed, for 500mg and batch label claim were well suited to be sustained release formulation. All of the batches were governed by diffusion through swollen matrix. REFERENCES 1. Koester L.S., Xavier, C.R., Mayorga, P., Bassani, V.L. Influence of β-cyclodextrin complexationon carbamazepine release from hydroxypropyl methylcellulose matrix tablets. Eur. J. Pharm. Biopharm. 55: 85-91, Wells, J.I. Tablet Testing. In Encyclopedia of Pharmaceutical Technology. Swarbrick, J., Boylan,J.C. (eds), Marcel Dekker Inc., New York,. 14, , Madden, H., Butler, J., Polli, J., Madden, S., Corrigan, O., Devane, J. Impact of dissolution medium on the release of a highly soluble drug from a hydrophilic matrix tablet. Pharm Sci AAPS, 1: 643, 1998.

7 Impact factor: 3.958/ICV: 4.10 ISSN: Bhalla, H.L., Handa, A.K. Development and Evaluation of Controlled Release Tablets of Metformin Hcl. Indian Drugs, 3: , Narasimhan, B Accurate Models in Controlled Drug Delivery Systems. Wise, D.L. (ed.). In Handbook of Pharmaceutical Controlled Release Technology. Marcel Dekker Inc., NY, pp , Giunchedi, P., Conte, U., La Manna, A. Carbamazepine Modified Release Dosage Forms. Drug Dev. Ind. Pharm. 17: , Controlled Drug Delivery, Fundamental and Applications. Robison, J.R., Lee, V.H.L. Marcel Dekker, Inc., New Cork, 11-42, , Hogan, J.E. Hydroxyl Propyl Methyl Cellulose. Sustained Release Technology. Vol. 15 (6 and 7), 1989, pp Reynolds, T.D., Mitchell, S.A., Balwinski, K.M. Investigation of the effect of tablet surface area/volume on drug release from HPMC controlled-release matrix tablets. Drug. Dev. Ind. Pharm, 28: , Ritger, P.L., Peppas, N.A. A simple equation for description of solute release I. Fickian and Non- Fickian Release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J. Control. Rel, 5: 23-36, Williams III, R.O., Reynolds, T.D., Cabelka, T.D., Sykora, M.A., Mahaguna, V. Investigation of Excipient Type and Level on Drug Release from Controlled Release Tablets Containing HPMC. Pharm. Dev. Tech, 7: , Wang. DS., Jonker. JW., Kato. Y., Kusuhara. H., Schinkel. AH., Sugiyama. Y., Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther, 30:510-5, Zolk O: Current understanding of the pharmacogenomics of Metformin.Clin harmacol Ther, 86: 595-8, Banker. G, Peck. G., Williams. E., et al. Microbiological considerations of polymer solutions used in aqueous film coating. Drug Dev Ind Pharm, 8: 41 51, Velazquez. D., Cruz. G., Torres. J., Martin-Polo. M., Temperature effects on the moisture sorption isotherms for methylcellulose and ethylcellulose films; J Food Engin, 48: 91 94, Raymond C Rowe, Paul J Sheskey, Marian E Quinn, Handbook of Pharmaceutical Excipients, 6th ed. Pg.no , , , , United States Pharmacopoeia XXX, 2002; Vol 1 and 2, Pg. no. 242,643,731.

8 Impact factor: 3.958/ICV: 4.10 ISSN: Nicole.Kavanagh., Owen Corrigan., Swelling and erosion properties of Hydroxypropylmethylcellulose (Hypromellose) matrices: influence of agitation rate and dissolution medium composition, Inter. J. Pharm, 279: , M Farouk, A., programmable drug delivery system for oral administration., Int. J. Pharm, 184: , 1999.