FORMULATION AND DESIGN OF METFORMIN HYDROCHLORIDE EXTENDED RELEASE TABLETS

 

{ DOWNLOAD AS PDF }

ABOUT AUTHORS
Goundla Uday Bhasker Goud1*, Jakkampudi Sri Venu Prakash1, Avadhanam Pranav Kumar2, Gangi Reddy Sreenivas Reddy2, Manikanta Sai Krishna2.
1Department of Industrial Pharmacy
2Department of Pharmaceutics
Bharat Institute Of Technology, Mangalpally, Hyd, Telangana, India.
gouds.uday04@gmail.com

ABSTRACT
Aim:
The current paper was an attempt to design a extended release dosage form of Metformin hydrochloride using various grades of hydrophilic polymers, hydroxy propyl methyl cellulose (HPMC K4M, HPMC K15M, HPMC K100M and HPMC K200M) and MCC.
Materials and Methods:
Laboratory scale batches of 4 tablet formulations were prepared by wet granulation technique. Precompression parameters of the granules were evaluated prior to compression. Tablets were characterized as crushing strength, friability, weight variation, thickness, drug content or assay and evaluated for in-vitro release pattern for 12 hr using Phosphate buffer of pH 6.8 at 37 ± 0.5°C.
Results and Discussion:
The results obtained revealed that HPMC K100M in formulation (F3) was able to sustain the drug release for 12 h and followed the Higuchi pattern quasi-Fickian diffusion. and charged for stability testing, parameters were within the limit of acceptance. There was no chemical interaction found between the drug and excipients during Fourier Transform Infrared Spectroscopy (FTIR).
Conclusion:
Hence it can be concluded that formulation F3 containing HPMC K100M is suitable for development of extended release tablets of Metformin Hydrochloride.

REFERENCE ID: PHARMATUTOR-ART-2272

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 11

Received On: 20/08/2014; Accepted On: 10/09/2014; Published On: 01/11/2014

How to cite this article: GUB Goud, SVP Jakkampudi, PK Avadhanam, GRS Reddy, MS Krishna; Formulation and Design of Metformin Hydrochloride Extended Release Tablets; PharmaTutor; 2014; 2(11); 112-119

INTRODUCTION
Diabetes a global public health problem is a chronic disease and is now growing as an epidemic in both developed and developing countries. Around 150 million people suffer from diabetes in the world out of which above 35 million are Indians. Current drugs used for managing TYPE II Diabetes and its precursor syndromes, such as insulin resistance, fall within five classes of compound such as the biguanides, thiazolidinediones, the sulfonylureas, benzoic acid derivatives and alpha glucosidase inhibitors. Metformin is an oral antidiabetic drug from the biguanide class[1]. Metformin is the most popular antidiabetic drug that requires controlled release owing to its short biological halflife of 3.4 ± 0.7 hours[2]. Metformin hydrochloride is an orally administered biguanide, which is widely used in the management of and the type -II diabetes, is a common disease that combines defects of both insulin secretion and insulin action. It is a hydrophilic drug and is slowly and incompletely absorbed from the gastrointestinal tract, and the absolute bioavailability is reported to be of 50% - 60%[3]. An obstacle to more successful use of metformin therapy is the high incidence of concomitant gastrointestinal symptoms, such as abdominal discomfort, nausea, and diarrhea that especially occurs during the initially period of treatment. The compound has relatively short plasma half life of 1.5-4.5 hours and the low absolute bioavailability of 50%-60%. Side effects, short half lives, low bioavailability and the need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 hrs might besufficient for daily dosing for metformin sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances[4].

Extended release drug delivery system achieves a slow release of the drug over an extended period of time or the drug is absorbed over a longer period of time.[5] Extended release dosage form initially releases an adequate amount of drug to bring about the necessary blood concentration (loading dose, DL) for the desired therapeutic response and therefore, further amount of drug is released at a controlled rate (maintenance dose, DM) to maintain the said blood levels for some desirable period of time.[6] Extended release drug delivery system (ERDDS) have emerged as an effective mean of enhancing the bioavailability and controlled delivery of many drugs. ERDDS play an important role in reducing the dosing frequency as well as by enhancing the biological half life of specific certain drugs. In recent years, various efforts were made to reduce the dosing frequency of certain patent drugs by this approach.[4,7]

The present study undertaken aims at the formulation development and evaluation of extended release tablets of metformin HCl, which releases the drug in a sustained manner over a period rime. different grades of Hydroxy Propyl Methyl Cellulose (HPMC) namely K4M, K200M, K15M, K100M andMicro crystalline cellulose were used for the preparation of tablets.

MATERIALS AND METHODS
Materials:
Metformin HCl was obtained from universal medicament, Nagpur, India. Microcrystalline cellulose (MCC PH 102), HPMC (K4M,K200M, K15M, K100M), Aerosil, povidone where purchased from S.D Fine Chem. Labs (Mumbai, India). HPMC (K15M and K100M) was obtained as gift sample from Apex Pharmaceuticals, Chennai, India. All other ingredients used throughout the study were of analytical grades and were used as received.

Methods
Calibration curve of metformin HCl:
Calibration curve of metformin HCl was prepared in 0.1N HCl and phosphate buffer of pH 6.8 at using spectrophotometric method at absorbance 233 nm of UV region.

Formulation of Metformin Hydrochloride Extended Release Tablets: Metformin Hydrochloride Extended release tablets were prepared by Wet granulation method. Accurately weighed Metformin Hcl, MCC and HPMC (of required grade) were sifted using # 60 and placed in separate poly bags. The sifted materials were mixed for 5 min and granulated with required quantity of binder by kneading method (Hand granulation) or in FBP. The granules were passed through sieve and dried at an inlet temperature of 80 0C and Product temperature of 50 0C in FBD, until the required moisture content is obtained. Then the granules are size reduced, using sieve#20.The granules were finally lubricated using magnesium stearate after sifting it through #60, for 5minutes. The lubricated granules were compressed into tablet each containing 500mg Metformin hydrochloride and a total weight of 800mg using 16.7 x 8.1 mm punches. The formulation of Metformin Hydrochloride extended release tablets are listed in (Table 1)[8]

Table no-1 Formulation of Extended Release Tablets of Metformin Hydrochloride

S.No

Ingredients

FORMULATION BATCH CODE

F 1

F 2

F 3

F 4

1

Metformin Hcl

500

500

500

500

2

HPMC K4M(mg)

200

-

-

-

3

HPMC K15M(mg)

-

200

-

-

4

HPMC K100M(mg)

-

-

200

-

5

HPMC K200M(mg)

-

-

-

200

6

Micro crystalline cellulose

80

80

80

80

7

Magnesium stearate

10

10

10

10

8

Aerosil

10

10

10

10

9

IPA

QS

QS

QS

QS

10

Water

QS

QS

QS

QS


TOTAL WT

800

800

800

800

PRECOMPRESSION PARAMETERS
The granules were evaluated for Angle of repose, Bulk density, Tapped density, Compressibility index and Hausner’s ratio.

Angle of repose[4,9]: Angle of repose is a relatively simple technique for estimation of the flow property of a powder. Powders with low angle of repose are free flowing and those with a high angle of repose are poorly flowing powders.10 gm of granules were passed through funnel and the pile was formed. The height and weight of the pile was measured and the angle of repose was calculated by using the formula:-

                                       h
Angle of repose (tan θ) =  -----
                                       r

Where, h and r are height and radiusof the pile respectively.
Angle of repose as an indication of powder flow properties.

Bulk density[9,10]: The powder sample (blend) under test was screened through sieve #18 and the sample equivalent to 20g was accurately weighed and filled in a 100ml graduated cylinder and the powder was leveled and the unsettled volume (V0) was noted. The bulk density was calculated in g/cm3 by the formula,

                              M
Bulk density (ρ0) =  ------
                             V0

Where,
M = mass of powder taken
V0= apparent untapped volume.

Compressibility Index[9]: Percentage compressibility or Carr’s index (CI) Based on the poured density and tapped density, the percentage compressibility of the granules was computed using the Carr’s compressibility index by the formula,

                            poured density-tapped density

Carr’s index (%) =    -----------------------------   X100
                                     poured density

Hausner’s ratio[11]: Hausner’s ratio is called as index of flowability and is Calculated using the formula,

                            V1
Hausner’s ratio =  -------
                            V2

Where V1 is the volume before taping and V2 is the volume after tapping.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


Pages

FIND MORE ARTICLES