Metformin hydrochloride

Formulation and evaluation of METFORMIN HCL sustained release tabs...

1. By:- G. TARUN KUMAR REDDY B.pharm ., “FORMULATION AND EVALUATION OF PROLONGED RELEASE OF METFORMIN HYDROCHLORIDE TABLETS ”

2. INTRODUCTION :- \ The drug delivery systems are those which control the rate of drug delivery, sustaining the duration of therapeutic activity and targeting the drug to the diseased tissue. Thereby leading the better therapeutic effect with minimum side effects. The different types of drug delivery systems are as follows:-

3. EXTENDED RELEASE TABLETS The medical advances have been made in the area of drug delivery with the development of novel dosage forms. The area of sustained drug delivery has granted as the most promising type of the drug delivery system. The sustained release or extended release drug delivery system can be solve problems concerning the targeting of a drug to a specific organ or tissue. The extended release tablets will provide controlling the rate of drug delivery.

4. The terms used for extended release tablets are:-

5. ADVANTAGES:- 1. Enhance product saftey . 2. Improved Efficacy. 3. Improved patient compliance. 4. More accurate compared to other conventional drug delivery systems. DISADVANTAGES:- 1. Stabilty Problems. 2. Expensive. 3. May Alter With The Food.

6. PHYSICOCHEMICAL PROPERTIES: IUPAC Name : N,N- Dimethyl imidodicarbonimidic diamide DRUG PROFILE Appearance White or almost white crystalline Powder Solubility Soluble in water Freely soluble as HCl salt Molecular formula C4H11N5 Molar mass 129.16 g mol−1 log P 1.254 State Solid Melting point 223-226 o C pKa 12.4 BCS CLASSIFICATION Class-III

7. MECHANISM OF ACTION

8. LITERATURE REVIEW David P Figgitt et al., The purpose of this research was to formulate and characterize solid dispersion (SD) of metformin hydrochloride using methocel K100M as the carrier by the solvent evaporation and cog- rinding method. Characterization was performed by Fourier transform spectroscopy (FTIR), ultraviolet, The optimized formulation was subjected to accelerated stability testing as per ICH guidelines. Basavaraj.k Nanjwade et al., To develop and characterize an oral Prolonged-release matrix tablet of metformin hydrochloride using a combination of a hydrophobic carrier and hydrophilic polymer and two types of formulation techniques.

9. P. K. Bhoyar et al ., An attempt was made to sustain the release of metformin HCl as well as to mask the bitter taste by complexation technique using strong cation -exchange resins. The drug loading into ion-exchange resin was optimized for mixing time, activation, effect of pH, mode of mixing, ratio of drug:resin and temperature. The resinate was evaluated for micromeritic properties, taste masking and characterized using IR. Using resinate sustained release tablets were.

10. AIM Formulation and evaluation of prolonged release of Metformin Hydrochloride Tablets. OBJECTIVE Under these considerations, objective of the work is To design the formula for Metformin Hcl ER tablets. To incorporate selected model drug candidates in the same formula and prepare tablets. To evaluate the prepared tablets of Metformin hydrochloride. To study the in-vitro dissolution profile of prepared tablets. Stability evaluation studies were carried out.

11. PLAN OF WORK Preformulation studies :- *API characterization   *Organoleptic evaluation   *Solubility   *Analytical evaluation   *Bulk density   *Tapped density   *Angle of repose   *Compressibility index    

12. Evaluation Of Tablets Post Formulation Studies:- Hardness Uniformity of thickness Friability Weight variation Content uniformity In vitro dissolution Stability studies.

13. Extented release tablets containing 500 mg of model drug were prepared with a total tablet weight of 750mg. Considering the pre-formulation studies and the literature survey conducted the excipients were selected and an attempt to produce prolonged released tablets. FORMULATION AND DEVELOPMENT

14. + ADD DILUENT

15. METHOD: The powder blend is subjected to drying and was compressed by direct compression method by using Standard concave punches in 8 Station Kambet KMPC8 tablet punching machine Punches of 17.5mm and 7mm diameter were used for compression. Tablet of 748mg and 753mg was prepared in different trials by adjusting hardness and volume screw of compression machine properly.

16. WET GRANULATION METHOD Drug + polymer Pass through sieve No:- 40 Add Diluent , half part of binder Then Pass through sieve(sieve No.40) DM water Prepare granules and lubricated it with Magnesium sterate (pre-sifted through sieve No. 60) mix 5 minutes Subject the blend for tablet formulation (compression)

17. METHOD:- Compress with punches in 8 Station Kambet KMPC8 tablet punching machine. Standard concave punches of 17.5mm, with breakline punches measuring the Tablet of 750mg,770mg,740mg and 760mg was prepared in different trials by adjusting hardness and volume screw of compression machine properly.

18. DEVELOPMENT OF METFORMIN OF PROLONGED RELEASE TABLETS Formula INGREDIENTS Mg/Tab(T1) API 500 Polyox-303 50 Lactose monohydrate 190 Mg Stearate 10 Total Weight 750

19. PRE-FORMULATION OF API I . Pre Compression Parameters 1.Angle of Repose The angle of repose has been used to characterize the flow properties of solids. This is the maximum angle possible between surface of pile of powder or granules and the horizontal plane. It was calculated using the following equation:- Tan θ = h / r θ = tan –1 h / r    Where, h = height of the powder heap r = radius of the powder heap θ = angle of repose

20. 2.Bulk density: Bulk de nsity defined as the mass of many particles of the material divided by the total volume they occupy. The total volume includes particle volume, inter-particle void volume, and internal pore volume. Bulk density is not an intrinsic property of a material. Bulk density = Weight of powder(g) / Bulk volume(ml)

21. 3.Tapped density:- Tapped densitiy of the drug was determined by pouring 25 gm through a glass funnel into a 100 ml cylinder. The cylinder was tapped from height of 2 inches until a constant volume was obtained. The volume occupied by the sample after tappings were recorded and the tapped density was calculated by the formula below Tapped density = Weight of powder(g) / Tapped volume(ml)  

22. 4.Carr’s compressibility index:- Compressibility is the ability of powder to decrease in volume under pressure. It is one of the method to determine the flow properties by comparing the bulk and tapped densities . % Compressibility Flow description <10 Excellent 11-15 Good 16-20 Fair 21-25 Passable 26-31 Poor 32-37 Very poor >38 Extremely poor

23. Carr’s index of each formulation was calculated according to equation given below:- Tapped density – Bulk density Tapped density X 100 Carr’s index =

24. II. Post- compression parameters: The quantitative evaluation of a tablet’s chemical, physical and bioavailability properties are important in the design of tablets and to monitor product quality. • General appearance:- The general appearance of tablets, its visual identity is essential for consumer acceptance, control of lot-to-lot uniformity and general tablet-to-tablet uniformity. The control of general appearance involves measurement attributes such as Tablet’s size Shape Color Presence or absence of odour Taste Surface textures & etc.

25. • Hardness or crushing strength:- The resistance of tablets to capping, abrasion or breakage under conditions of storage, transportation and handling before usage depends on its hardness. It is measured either by Monsanto or Stokes hardness tester , by applying pressure diametrally to the tablet. Monsanto Hardness Tester

26. RESULT IDENTIFICATION OF DRUG: By UV Spectroscopy: Determination of  max of Anti hyperglycemic agent: On the basis of preliminary identification test the drug scanned and it was concluded that the drug had  max of 232 nm which was equal to  max 232nm as reported (std.) . SPECTRUM POINT PICK METHOD

27. STABILITY STUDIES The stability studies were carried out by storing in HDPE containers under the Accelerated stability conditions of 40ºC /70% RH for a period of 1 month. The tablets were evaluated for the parameters like weight variation, hardness, friability, thickness, and percentage of drug content were evaluated for initial, 1 st , 2 nd , 3 rd and 1month. The tablets displayed all parameters of optimized formulation F10 within specified limits indicating the stability of the formulation . Parameters 1 st week 2 nd week 3 rd week 4 th week Weight variation (mg) 750±5 750±4 750±4 750±4 Thickness (mm) 5.75±0.6 5.75±0.7 5.75±0.7 5.74±0.6 Hardness (N) 180 ± 10 190 ± 10 185±10 180 ± 20 Friability (%) 0.045 0.15 0.15 0.015 Drug Content (%) 97 96 95 94 Stability Studies Of Metformin Prolonged Release Tablets

28. Stability Effect On In-Vitro Dissolution Of Optimized Formulation (F10) at 1,2,3&4 week . Time (Hours) % Drug Release 1 st week 2 nd week 3 rd week 4 th week 1 30 25 28 27 2 42 40 39 44 3 54 54 52 53 6 76 773 74 74 10 98 96 96 95 Stability Effect On In Vitro Drug release profile of Trial-10

29. BIBLIOGRAPHY United States pharmacopoeia (2008) Bulk density and tapped density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-232. Indian Pharmacopoeia (2012) Uniformity of weight of single dose preparations, Friability, 2010, vol-1, page no: 140, 192-193. Lachman L. and Lieberman H.A., Pharmaceutical Dosage Forms, In; Tablets, Vol. 2, Marcel Dekker, Inc., New York ,1989 pp.367-414 Martin,A .; Physical pharmacy; Fourth edition ; PP 444-445. www.wikipedia.org/wiki/tablets www.pharmainfo.net/tablets/types-tablets Remington The Science and Practice of Pharmacy, 21 st edition Vol.-1, Page No.1178-1198 www.Drugbank.com

30. Brahmankar D.M., Jaiswal S.B., “ Biopharmaceutics & Pharmacokinetics”; First Edition; p-335 (1995). Tripathi KD, Essential of medical pharmacology, 5th ed.New Delhi: Jaypeebrothepublishing house;2003, 254-275. United States pharmacopoeia (2012) Bulk density and tapped density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-232. Indian Pharmacopoeia (2012) Uniformity of weight of single dose preparations, Friability, 2010, vol-1, page no: 140, 192-193. British Pharmacopoeia (2012) Angle of repose, vol-5, Appendix-A465.

31. http://www.researchwikis.com/Generics_Market_Analysis_Marketing_ Research. United States pharmacopoeia (2012) Bulk density and tapped density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-232.