Journal of Pharmaceutical Research International

33(59B): 397-405, 2021; Article no.JPRI.80157

ISSN: 2456-9119
(Past name: British Journal of Pharmaceutical Research, Past ISSN: 2231-2919,
NLM ID: 101631759)

Formulation, Characterization and Release

Behaviour of Metformin Hydrochloride Modified
Release Tablet by Using Hydrophilic Polymers
J. Thirumaran a*, S. Tamilarasi a, S. Punitha a, T. Sivakumar a, C. N. Marimuthu b
and D. Kiruthika c
a
Department of Pharmaceutics, Nandha College of Pharmacy, Erode, Tamil Nadu, India.
b
Nandha Engineering College, Erode, Tamil Nadu, India.
c
Nandha College of Physiotherapy, Erode, Tamil Nadu, India.

Authors’ contributions

This work was carried out in collaboration among all authors. All authors read and approved the final
manuscript.

Article Information
DOI: 10.9734/JPRI/2021/v33i59B34395

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Received 08 October 2021

Original Research Article Accepted 17 December 2021
Published 18 December 2021

ABSTRACT

Amongst the many public health problems, the diabetes mellitus is considered as a chronic life-
style related disease which is now growing as an epidemic in both developed as well as developing
countries. The current study is about formulation of metformin hydrochloride tablet to confirm their
sustained release property by using various polymers. The tablets are prepared by granulation
techniques using binding solution containing polyvinyl pyrolline K30. The possible interaction
between the pure metformin hydrochloride and polymers are identified by Fourier transform-
infrared spectroscopy. Tablets were formulated with different polymers like Hydroxy propyl methyl
cellulose K100 and sodium carboxymethyl cellulose. Matrix prepared with high concentration of
HPMC K100 polymer retards the drug release up to 6 h at 59 %, but the formulation 2 (F2) showed
72.72% of drug release in 6 h. The release of drug from the F2 formulation was found to be
prolonged drug release when compared to other formulations. Hence our study conclude that the
HPMC K100 polymer containing formulation showed good sustained release property owing to the
high gel strength and well high viscosity nature of the polymer.

Keywords: Metformin hydrochloride; HPMC K 100; PVP K 30; CMC; sustained release tablet.
_____________________________________________________________________________________________________

*Corresponding author: E-mail: thiru.mrn@gmail.com;

 Thirumaran et al.; JPRI, 33(59B): 397-405, 2021; Article no.JPRI.80157

1. INTRODUCTION Lactose, PVP K30, talc, aerosil, sodium

hydroxide and sodium CMC were generous gift
Diabetes mellitus is a chronic disease suffered sample from Nice chemicals, Cochin, Kerala.
by approximately 150 million people out of which Magnesium stearate was get from loba
35 million people are Indians. The available chemicals, Mumbai. UV Spectrophotometer, FT-
antidiabetic drugs are used to treat diabetes IR, Type II Dissolution apparatus, tablet
mellitus and insulin resistance. The antidiabetic compression machine.
drugs are classified as biguanides,
thiazolidinediones, the sulfonylureas, benzoic 2.1 Parameters for Preformulation
acid derivatives and alpha glucosidase inhibitors.
The biguanide drug, metformin is currently Precompression study parameter of the pre-
prescribed by most of the physicians worldwide. formulation was determined to find out the flow
An ideal drug delivery formulation should release and compression properties of granules before
required amount of drug inside human body to compressing into tablet form Bulk density, tapped
desired therapeutic effect. Nowadays, sustained density, angle of repose, compressible index,
release dosage formulations are main focus of Hausner ratio.
the pharmaceutical research field to avoid
noncompliance by the patient and to reduce 2.2 Bulk Density
adverse drug reactions. The novel sustained
release dosage form should be able to maintain The 25 gram of the drug is weighed after passing
drug concentration in blood and tissue for through sieve (no. 20). The drug was then
extended or sustained period of time. The ideal transferred into a graduated cylinder (100 ml).
SR dosage form is obtained by trying "zero The powder is carefully leveled without
order" release dosage form without the influence compaction and apparent volume (Vo) is
of the delivery system [1-4]. measured. The apparent bulk density (gram per
ml) is calculated by dividing powder weight by
The oral antidiabetic drugs are formulated as
bulk volume [4].
tablets and capsules. Those tablets and capsules
are modified into controlled drug delivery
formulation and sustained drug delivery 2.3 Tapped Density
formulation. Matrix tablets are widely
acknowledged for oral controlled release tablet, Metformin hydrochloride (25 gm) is weighed after
as they are easy to formulate. The controlled passing through the sieve (no. 20) and
release dosage forms are formulated using transferred into graduated cylinder (100 ml). The
polymers and release-retarding materials as cylinder is then tapped mechanically using
matrix. The rate of drug released from ideal oral density tester and the drug is allowed to settle.
sustained release formulations is based on the The tester provided a fixed drop of 14 ± 2 mm at
polymer concentration. The intrinsic properties of a rate of 300 drop per minute. Again, the cylinder
the drug or the situation of GI tract should not is tapped for 500 and 750 times, respectively and
affect the formulation. The drug molecules initial volumes (V, V1) were measured [10, 11]. If
exhibited higher permeability across the the difference between the volumes (V and V1)
gastrointestinal epithelium. The absorption rate was less than 2 %, then the obtained volume
of the drug is controlled by the rate of drug was considered as final volume (V2). The final
released from the formulation [5-9]. tapped density (gram per ml) was determined by
dividing weight of the powder by final tapped
Our present study focused to formulate the volume [4].
metformin hydrochloride tablet to confirm their
sustained release property by using various 2.4 Angle of Repose
polymers such as, Hydroxy propyl methyl
cellulose K100 and sodium carboxymethyl The angle of repose ( ) is measured by fixed
cellulose based on their high gel strength and funnel method by adjusting the height of the
viscosity properties. funnel in order to touch the apex of the granular
heap. The prepared granules flowed freely
2. METHODOLOGY through the funnel and the angle of repose is
calculated by using the below formula.
Metformin drug was purchased from Himedia lab
pvt ltd., Mumbai and HPMC K 100 was
purchased from phoenix Pharma, Pondicherry. = [4]

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Where, h is the height of the granular heap and r thickness, tablet friability and dissolution rate of
is the radius of the granular circle. the compressed tablet were evaluated [17-20].

2.5 Compressible Index (Carr’s Index) 2.7 In vitro Dissolution Studies

Carr’s Index is a parameter to measure the flow The in-vitro drug release profile of the prepared
properties of the powder and it is measured sustained release tablet is measured using USP
using below equation: type II dissolution apparatus. The phosphate
buffer was filled in the basket of apparatus as the
I = (Dt- Db/ Dt) X 100 o
dissolution medium at 37 ± 0.5 C for 6 hours[17-
18] For every one hour intervals, sample (5 ml)
Where, Dt is the tapped density of the powder was withdrawn from the dissolution medium and
and Db is the bulk density of the powder [4]. replaced with fresh buffer solution to maintain
constant volume. After filtration, dissolution was
2.6 Hausner Ratio measured using UV spectrophotometer.
Hausner ratio is the flowability of a powder or
2.7.1 Properties of optimized sustained
granular material measured by the below given
release tablets
formula:

Hausner ratio = Dt/ Db The compressed tablets are checked for quality
control parameters (weight variation, thickness,
2.6.1 Drug excipients compatibility studies hardness, friability, drug content, and in-vitro
drug release behavior).
The drug-excipient compatibility is determined
using FT-IR. The drug and excipients are mixed 2.7.2 Hardness
with KBr pellets and scanned at a speed of 400-
-1 The hardness of the tablet is measured by tablet
4000 cm [12-16]. The peak values, spectra and
the functional groups of the mixture are crushing load using the tablet hardness tester
compared with standard values. (Pfizer hardness tester). The tablet crushing load
is the load required to break the tablet.
2.6.2 Fabrication of sustained release tablet
containing metformin 2.7.3 Weight variation test

The sustained release formulation of metformin Tablets are randomly selected from each
was prepared by wet granulation method by formulations and weighed separately. The
mixing with various ingredients and various average weight of tablet is determined from the
batches listed in the Table 1. measured values.

All the ingredients were thoroughly blended with 2.7.4 Friability

addition of PVP K 30 solution and then
magnesium stearate and talc were added. The The friability of the tablets were measured using
blend is compressed into tablets with 16/32 flat Roche friabilator™ at 100 rpm. The tablets are
punches by keeping average weight of 700 mg. weighed again and percentage friability was
The variation in weight, tablet hardness, tablet calculated using the below formula:

Table 1. Formulation of metformin hydrochloride sustained release tablets

Ingredients F1 F2 F3 F4 F5 F6 F7
Metformin 500 mg 500 mg 500 mg 500 mg 500 mg 500 mg 500 mg
HPMC K100 120 mg 115 mg - - - - -
Sodium CMC - - 105 mg 110 mg 115 mg 120 mg 125 mg
Lactose 42 mg 42 mg 42 mg 42 mg 42 mg 42 mg 42 mg
PVP K30 15 mg 20 mg 30 mg 35 mg 40 mg 45 mg 50 mg
Magnesium Stearate 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg
Talc 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg
Aerosil 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg
Distilled Water q.s q.s q.s q.s q.s q.s q.s

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 Thirumaran et al.; JPRI, 33(59B): 397-405, 2021; Article no.JPRI.80157

assigning to –OH groups, and sodium CMC

-1
showed 3419.56 cm corresponding to –OH
groups. In case of drug and polymer
2.8 Estimation of Amount of Drug composition, the broadening of bonds appeared
-1
at ranges of 3523.70, 3371.34, 3294.19 cm ,
Tablets (10) from each formulation are respectively. This can be inferred due to
powdered. The phosphate buffer (pH 6.8) was intermolecular hydrogen bonding between drug
used to dissolve the powdered tablets. The and polymers. The result concluded that there
diluted solution was analyzed by UV and DBSM was no chemical interaction between drug and
at 233 nm [21-23]. polymers, shows the formulated tablet (F2) more
stable (Figs. 1-4).
2.9 Thickness
3.3 Post Compression Parameters
Size and thickness of the tablet were measured
using screw gauge. The thickness of tablet The results of parameters of compressed tablets
obtained was related to tablet hardness. are illustrated in Table 3.

2.10 Drug Release Kinetic Profile 3.4 In-vitro Dissolution Profile

The release kinetics of the tablet at zero order
In-vitro release data from controlled release
and first order were measured using Higuchi and
formulation were carried out for six hours and
Korsmeyer-peppas model [23-25].
graphically represented as percentage drug
release verses time profile. Dissolution rate of
3. RESULTS pure metformin is very low. Only 27.64% of the
drug was released in phosphate buffer at the
3.1 Pre-formulation Studies time end of six hours. The sustained release of
drug from the formulation rate is increased more
3.1.1 Properties of compressed granules than the pure drug, due to the increase in surface
of the drug and possible better contact with
The properties of granules before compression polymer between the formulations and
are given in Table 2. The obtained result dissolution medium.
indicated that the flow properties of powder was
better for smooth tablet compression. The results of dissolution studies indicated that
F1-F7 released 56.89%, 59.28%, 72.72%,
3.2 Compatibility Studies 63.25%, 56.25%, 51.56% & 54.98% of drugs,
respectively. Dissolution studies prove that our
The FT-IR spectra of metformin HCl, HPMC modified tablet formulation F2 have shown
K100, sodium CMC and their composition was 72.72% of drug in six hours. The result showed
measured. It is shown that a high intense that considerable amount of drug was released
stretching frequency occurring at 3371.34 and for a period of up to six hours. Minimum amount
-1 +
1625.88 cm correspond to –OH and –NH3 of drug released within two hours in phosphate
groups is present in metformin HCl. CH showed buffer (pH 6.8). The release of formulation F2
-1
1475.44 cm corresponding to NH3+ groups, was prolonged than the other formulation
-1
HPMC K100 showed peak at 3445.56 cm showing the Fig. 1.

Table 2. Pre-compression parameters

Formulations Bulk density Tapped density Compressibility Hausner Angle of

3
(g/ml) (g/cm ) Ratio Repose
F1 0.53 0.62 12.35 1.14 22.5
F2 0.51 0.60 13.40 1.13 24.7
F3 0.57 0.65 12.48 1.06 25.9
F4 0.54 0.62 13.40 1.13 24.6
F5 0.49 0.60 12.42 1.11 22.6
F6 0.47 0.61 12.56 1.10 23.6
F7 0.45 0.63 13.20 1.09 21.6

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Table 3. The results of parameters of compressed tablets are illustrated

Formulation Weight Hardness Thickness (mm) Friability (%)

2
Variation (%) (Kg/cm )
F1 710 ± 10 4.34 ± 0.35 4.96 ± 0.03 0.547 ± 0.27
F2 700 ± 10 4.81 ± 0.12 4.98 ± 0.02 0.57 ± 0.19
F3 720 ± 10 3.79 ± 0.52 4.97 ± 0.02 0.273 ± 0.35
F4 710 ± 10 3.81 ± 0.47 5.01 ± 0.01 0.731 ± 0.11
F5 700 ± 10 4.45 ± 0.51 5.22 ± 0.05 0.621 ± 0.12
F6 705 ± 10 5.66 ± 0.40 5.25 ± 0.03 0.581 ± 0.18
F7 710 ± 10 6.70 ± 0.42 5.38 ± 0.01 0.430 ± 0.19

Fig. 1. FTIR of metformin

Fig. 2. FTIR of metformin +HPMC K100

3.5 Drug Release Kinetic Profile The release rate kinetic data of F2 formulation
was found to be the best when compared to
The kinetic data of the drug formulation was other formulation as represented in Fig. 3. As
checked in zero order, first order, Higuchi and shown in drug release data, the drug release of
Korsemeyer and peppas model, respectively. F2 formulation is best formulation suitable for first
The results were showed in the histogram graph order kinetic equation with highest linearity
2
Fig. 2. (r =0.988).

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Fig. 3. FTIR of formulation 2

Fig. 4. Metformin+sodium cmc FTIR

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Fig. 5. In-vitro drug release profile

1.02

0.98
ZERO ORDER REACTION

0.96 FIRST ORDER REACTION

HIGUCHI DIFFUSION
0.94
KORSEMEYER PEPPAS
0.92

0.9
F1 F2 F3 F4 F5 F6 F7

Fig. 6. Drug release kinetic profile

As shown in Fig. 3, the plot for Korsmeyer- These formulations showed good flow properties
Peppas equation indicated a respectable linearity with better release of drugs and kinetics. In the
2
(r = 0.982). The diffusion exponent “n” fitted in-vitro drug release formulation F2 showed
0.982 that indicated the diffusion mechanism is 72.72% of drug release in 6 hrs. The release of
Class II transport. This indicated that the drug drug from the F2formulation was prolonged
release is better for diffusion and dissolution. compared to that of other formulations. It would
be desirable to study that formulation containing
4. CONCLUSION optimum concentration of polymer will release
the drug after prolonged time interval compared
In this current study, Metformin hydrochloride with high concentration polymers. Compared to
sustained release tablet was successfully all formulation from F1 to F7, only F2 has found
designed by wet granulation technique. Tablets to be ideal concentration of the sustained release
were formulated with different polymers with behavior. In previous study the HPMC K100 had
different composition to achieve, the target. higher viscosity shows that the formulated tablet

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affecting the drug release pattern in order to Formulation and evaluation of Metformin
[
enhances the sustained action 26]. Similarly in HCL sustained release tablets. Int J
our work also proves that sustained release Biopharmaceutics. 2013;4(2):73-79.
action was achieved by HPMC K 100. 7. Rohini D, Alexander S, Chandrasekar JN,
Preparation and In-vitro evaluation of
DISCLAIMER sustained release tablet formulation of
Metformin hydrochloride. Asian J Pharm
The products used for this research are clin Res. 2012;5(1):45-48.
commonly and predominantly use products in our 8. Madhusudhan R, Ayesha S, Surya B,
area of research and country. There is absolutely Manasak J, Srinivasa BP. Formulation and
no conflict of interest between the authors and evaluation of sustained release matrix
producers of the products because we do not tablet of Metformin Hydrochloride. Ind J
intend to use these products as an avenue for Res Pharm and Biotec. 2013;1(2):197-200.
any litigation but for the advancement of 9. Ganesh G, Sureshkumar R, Jawahar N,
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tablet of Diclofenac sodium using Natural
CONSENT
Polymer. J Pharm Sci and Res. 2010;2(6):
360-68.
It is not applicable.
10. Bhupendra P, Rakesh P, Dhaval P, Payal
ETHICAL APPROVAL S. Metformin Hydrochloride sustained
release matrix tablet using different
As per international standard or university Polymers. E-Journal of Science and
standard written ethical approval has been Technology. 2013;8(4):61-72.
collected and preserved by the author. 11. Upadhyay U, Rathore KS. Formulation and
evaluation of sustained release matrix
COMPETING INTERESTS tablet of Metformin hydrochloride, Pharm
Chem J. 2014;1(2):5-13.
Authors have declared that no competing 12. Md. Asaduzzaman, Md. Rezowanur
interests exist. Rahman, Md. Saifur Rahman Khan, S.M.
Ashraful Islam, Development of sustain
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