Sharma et al Journal of Drug Delivery & Therapeutics.

2019; 9(3-s):374-385

Available online on 15.06.2019 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted
non-commercial use, provided the original work is properly cited

Open Access Research Article

To study the comparative dissolution profiles of sustained release tablets of
metformin hydrochloride by using various hydrophilic polymers
Sharma Diksha*1, Dev Dhruv1, Prasad D.N.2, Hans Mansi1, Sahore Ruchika1
1 Department of Pharmaceutics, Shivalik College of Pharmacy Nangal, Punjab, India
2 Department of Chemistry, Shivalik College of Pharmacy Nangal, Punjab, India

ABSTRACT
In this research study an attempt was made to formulate sustained release matrix tablets of Metformin Hydrochloride as it possesses relatively
shorter plasma half-life, low bioavailability. The sustained release formulations of the drug were capable of maintaining the plasma level for 8-
12 hours. The overall objective of this research was to formulate the tablet by using various hydrophilic polymers i.e. Xanthan gum, Guar gum,
Aloe barbadensis and Methocel K4M. Tablets were prepared by wet granulation method. In Vitro studies were performed by USP XX apparatus
I, basket and the data was analyzed using zero order, first order, and Korsmeyer and Higuchi models. Nine formulations were made, out of
which F-9 formulation which was composed of Aloe Barbadensis in the ratio of 1:2, with combination of other polymers (xanthan gum, gu ar
gum and methocel K4 M) showed maximum drug release within 12 hours with sustained release profile because Aloe barbadensis showed
maximum swelling followed by entanglement of polymers chains, thus gave maximum gel strength which provides main retarding factor for the
drug release. The use of three polymers (xanthan gum, guar gum and methocel K4M) alone in the different formulations i.e. from F-1 to F-6 was
not able to sustain the drug release because of their rapid solubilization in acidic pH leads to pores in the matrix, finally causes surface erosion
and initial disaggregation of the matrix tablet prior to gel layer formation around tablet core causes rapid release of the drug within 1 hour as
compared to F-9 formulation.
Keywords: Sustained drug delivery system, Aloe Vera, Methocel K4M, Xanthan gum, Guar gum and Metformin HCl.

Article Info: Received 01 May 2019; Review Completed 31 May 2019; Accepted 06 June 2019; Available online 15 June 2019
Cite this article as:
Sharma D, Dev D Prasad DN, Hans M, Sahore R, To study the comparative dissolution profiles of sustained release tablets
of metformin hydrochloride by using various hydrophilic polymers, Journal of Drug Delivery and Therapeutics. 2019; 9(3-
s):374-385 http://dx.doi.org/10.22270/jddt.v9i3-s.2856

*Address for Correspondence:

Sharma Diksha, Department of Pharmaceutics, Shivalik College of Pharmacy Nangal, Punjab, India

INTRODUCTION release of the drug product is designed so that the release

rate of maintenance dose is equal to the elimination rate.
The sustained release dosage form are designed in such a The constant blood levels can be achieved from controlled
way that they continuously release the drug over an release system and the prolonged release of the dosage form
extended period of time after the administration of a single reduces the fluctuation in plasma by slowing down its
dose of a dug. The basic goal of this therapy is to provide a absorption rate so that its slower drug release rate can be
steady state blood or tissue level which is both achieved as well as can be maintained [3 - 5].
therapeutically effective and non-toxic for prolonged period
of time and finally improves patient compliance as well as Metformin hydrochloride is an orally administered
toxicity to a large extent. The basic rational of sustained drug biguanide which is used in the management of type-II
delivery system is to alter the pharmacokinetics and diabetes, a disease that combines defects of both insulin
pharmacodynamics of the pharmacologically active drug secretion and insulin action. Metformin HCl does not causes
moieties by modifying their molecular structure or hypoglycemia at any reasonable dose, thus it is called as an
physiological parameters. Basically a sustained release oral antihyperglycemic rather than a hypoglycemic drug. It is a
dosage form is designed to rapidly release pre-determined hydrophilic drug which is slowly as well as incompletely
fraction of the total dose (loading dose) into gastrointestinal absorbed from the gastrointestinal tract, and the absolute
tract, which will produce the desired pharmacological bioavailability is reported to be of 50-60 %. Metformin HCl
response as promptly as possible and the remaining fraction has relatively short plasma half-life of 1.5-4.5 hours and the
of the total dose (maintenance dose) is then released at a low absolute bioavailability of 50-60 %. The side effects,
controlled rate to maintain the steady state. The controlled short half-lives, low bioavailability makes the administration
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two to three times a day when larger doses are required Methods
which can decrease patient compliance, thus sustained
release products are needed for metformin which can Preformulation Studies
prolong its duration of action, improve patient compliance Preformulation studies is described as the method of
and reduces toxicity of drug in the body . The natural gums optimizing the delivery of drug by determining the
are widely used in the preparation of sustained release physiochemical properties of the active compound that can
tablets. Xanthan gum, Guar gum and Aloe Vera were the affect drug performance as well as development of an
natural gums used in this research work. Xanthan gum are efficacious, stable and safe dosage form [1].
obtained from Xanthomonas campestris. Guar gum is
derived from guar plant Cyamopsis tetragonolobus (i.e. Physical appearance
Cluster bean), finds wide application as stabilizer and The drug metformin hydrochloride was visually observed
thickener in pharmaceutical industry. Aloe Vera is obtained and was found to be
from the mucilage of leaves of Aloe barbadensis. These
natural gums are reported to have antidiabetic effect on Color: White hygroscopic crystalline powder.
humans which helps to potentiate the effect of Metformin Odor: Odorless
HCl. The use of these hydrophilic polymers alone for the Taste: Bitter taste.
purpose of extending drug release for the highly water Determination of max
soluble drugs is restricted due to rapid diffusion of the
dissolved drug through its gel network. It was found that The absorption maxima of Metformin Hydrochloride was
dried mucilage of Aloe barbadensis can potentiate the scanned between 200-400nm. The max of the drug was
antidiabetic effect to a great extent as well provides determined by UV- visible spectrophotometric method to
maximum sustained effect because of its excellent gelling obtain the structural information regarding the
strength [6, 7]. chromophoric part of Metformin Hydrochloride.
The main objective of the present work was to formulate the Preparation of calibration curve of Metformin in
drug, Metformin with various hydrophilic natural and Phosphate buffer of pH 6.8
synthetic polymers alone or in combination. As according to
Metformin Hydrochloride concentration in the solution was
BCS classification Metformin falls under the category III
determined by UV- Visible spectrophotometer by reading
(High solubility and low permeability). The high solubility is
the instrument at 233nm. The standard curves of Metformin
the main obstacle for its sustained action and high
Hydrochloride were prepared in water and phosphate buffer
bioavailability but low permeability potentiates its sustained
pH 6.8.100mg of Metformin Hydrochloride was correctly
action. The use of various natural polymers provides pH
weighed and transferred in to 100ml of standard flask and
independent drug release. Aloe barbadensis was chosen to
then volume was made up to 100ml with the phosphate
be best fit polymer for retarding the drug release with
buffer. Pipette out 1ml again from the prepared solution and
combination of other used polymers such as xanthan gum,
this will serve as stock solution for the dilution make up.
guar gum and methocel K4M. These polymers used alone
Finally the dilutions were made by pipetting out 1ml, 2ml,
cause’s sudden burst release of drug because of their rapid
3ml, 4ml and 5ml from the stock solution, and further they
solubilization in acidic pH and initial disaggregation of drug
were diluted to 10ml with phosphate buffer with pH 6.8.
particles before the gel formation of the used hydrophilic
polymer. Tablets were prepared by wet granulation method; Fourier- Transform Infrared Spectroscopy (FTIR)
this method is a process of forming granules by binding the
powders together with an adhesive rather than compaction. IR spectroscopy is the best technique for qualitative
Liquid bridges are formed between particles and tensile compound identification. It gives information about the
strength of these blends increases with the amount of liquid group present in the particular compound. IR study was
binder. Surface tension and capillary forces are responsible performed for identification and structural analysis of the
for initial granule formation and their strength. Granules are procured drug using Shimadzu- 1800 FTIR. The potassium
said to have improved free flowing properties as well as bromide (KBr) disk technique was employed using 100mg of
decreased dust problems. Various excipients used such as spectroscopic grade dried KBr. KBr was ground into a fine
Microcrystalline Cellulose which is most increasingly used in powder using a mortar/pestle and compressed into disc
formulating sustained release dosage forms for the matrix under hydraulic pressure at 10,000psi. Metformin
tablet drug delivery. Hydrophilic polymers are included Hydrochloride and drug excipient mixture were placed on
necessarily in tablets in order to form a viscous, gelling layer the KBr disc with the help of capillary tube. Each KBr disc
which helps to retard the water penetration and acts as a was scanned at a resolution of 400 cm-1 and characteristic
barrier to drug release. The majority of drug release occurs bands were recorded.
by diffusion through and erosion of this barrier [7]. Solubility
MATERIALS AND METHODS The solubility of a drug in a specific solvent is measured in
Materials terms of saturation solubility.

Metformin HCl was obtained as a gift sample from Swiss Table 1: Solubility profile for metformin hydrochloride
Garnier Life Sciences Mehatpur, Himachal Pradesh. in water, isopropyl alcohol, methylene chloride, ethanol
Microcrystalline cellulose, Aerosil, Talc were also obtained and acetone are:
from Swiss Garnier Life Sciences Mehatpur, Himachal S. No. Solvent Solubility
Pradesh. Xanthan gum, Guar gum was obtained from Dabur 1. Water Freely soluble
Pharmaceuticals, Haridwar. Aloe barbadensis was obtained 2. Isopropyl alcohol Freely soluble
from Botanical garden of Shivalik College of Pharmacy, 3. Methylene chloride Freely soluble
Nangal. 4. Ethanol Slightly soluble
5. Acetone Not soluble

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Saturation solubility is the extent of solubility of the drug Melting point

beyond which addition of any more amount of solute does
not increase concentration of solution. The solubility of Melting point of the drug was determined by capillary fusion
Metformin HCl was tested in various solvents. A definite method; one sided closed capillary filled with drug and put
quantity (10 mg) of drug was dissolved in 10ml of each into the Melting point apparatus. Temperature was noted at
which drug converts into liquid.
investigated solvent and shaken at 25°C for 24 hours in a
water bath shaker until the equilibrium was obtained.

Table 2: Melting point of metformin hydrochloride

Reported value Experimental value Mean value
224°C 223°C 224°C 224°C 224°C

Various Pre compression parameters in such a way that the tip of the funnel just touch the apex of
the powder blend. The powder blend was allow to flow
Bulk density
through the funnel freely on the surface. The diameter of the
It is defined as the ratio of total mass of powder to the bulk powder cone was measured and the angle of repose was
volume of powder. It is calculated by pouring the weighed calculated using the following equation. Radius of heap (r)
powder (passed through standard sieve # 20) into a was measured and angle of repose (ϴ) was calculated using
measuring cylinder and initial weight was noted. This initial the formula [12].
volume was called the bulk volume. From this the bulk ϴ = tan-1 height /radius
density was calculated according to formula mentioned
below. It is expressed in gm/ml is given by Formulation of Sustained Release Tablets of Metformin
Hydrochloride by wet granulation method Drug was
Bulk density= M/Vb
accurately weighed and passed through # 40 sieve. The
Where, M and Vb are mass of powder and bulk volume of the screened powder was transferred into the mortar pestle and
powder respectively [12]. mixed for 5 minutes. The corresponding amounts of
polymers (Methocel K4M, guar gum, Xanthan gum, and Aloe
Tapped density Vera powder) and microcrystalline cellulose were accurately
Tapped density is defined as the ratio of total mass of the weighed, screened through screen # 40, added to mortar
powder to the tapped volume of the powder. Volume of pestle and mixed. 5% alcoholic solution (IPA) of polyvinyl
powder was measured by tapping the powder for 750 times pyrrolidone (PVP K30) was then added to the powder
and the tapped volume was noted if the difference between mixture as binder forms a wet mass consistency. The wet
these two volumes is less than 2%. If it is more than 2%, mass was passed through a # 10 sieve and the resulting
tapping is continued for 1250 times and tapped volume was granules were placed on trays for drying into the oven at
noted. Tapping was continued until the difference between 50°C for 10 minutes. The dried granules were passed
successive volumes was found to be less than 2% (in a bulk through # 22 sieve. The dried granules and the
density apparatus). It is mainly expressed in the units of corresponding amount of magnesium stearate, talc, and
gm/ml and is given by. aerosil were accurately weighed and then mixed properly.
Mixture was compressed into tablets using an instrumental
Tapped density = M/Vt tablet press and tablets were collected during compression
Compressibility index for in process testing (weight and hardness) [2].

The compressibility index of the powder was determined by Separation of Aloe gel powder from fresh leaves of Aloe
Carr’s compressibility index [12]. Vera

Carr’s index (%) = Tapped density-Bulk density/Tapped Freshly cut leaves of Aloe barbadensis were washed
density×100 thoroughly with water to remove the debris of soil and then
cut open to collect the inner parenchymatous tissue (gel) of
Hausner ratio the leaf. The gel was then washed with distilled water and air
dried under ambient condition for 12 hours and then at 80°C
Bulk density and tapped density were first calculated and
in a tray dryer for 4 hours to get solid dry mass. Dried solid
finally Hausner’s ratio was calculated. It indicates the flow
mass was then converted into fine powder by mechanical
properties of the granules and is calculated by taking the
grinding and passed through sieve # 85.
ratio of tapped density to the bulk density. Hausner’s ratio is
an indirect index for the ease of powder flow. It is calculate At the end it was decided to prepare final batches F-7, F-8
by the given formula [12]. and F-9 with the combination of above polymers i.e. guar
gum, xanthan gum, methocel K4M and finally the most
Hausner ratio= Tapped density /Bulk density
suitable natural mucilage powder of Aloe Vera with the
Lower Hausner’s ratio (<1.25) indicates better flow increasing ratios with respect to the quantity of drug i.e. (1:1,
properties than high ones (>1.25). 1:1.5, and 1:2). The other three polymers were kept in the
same quantity for these three final batches as depicted in the
Angle of Repose table 3 and 4 [9].
Angle of repose of pure drug was determined by using fixed Role of combination of the polymers in the final batches
funnel method. The blend was allowed to pour through a
funnel that can be raised vertically until a maximum cone The maximum release or the ability to sustain small amount
height (h) was obtained. The height of the funnel was adjust of drug with the three mention polymers can be attributed to
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the effect of sudden erosion of the matrix after the swelling The extent and degree of swelling was measured in terms of
of these natural polymers. As high viscosity Methocel K4M is % (percentage) weight gain by the tablet. The swelling
able to attribute to high gel layer formation which serves as a behaviors of the formulations were studied. One tablet from
protective barrier to both the influx of water and the efflux of each formulation was kept in a petridish containing pH 6.8 or
the drug in the solution. Aloe Vera contributes to both the 7.4 phosphate buffer, as the drug also shows good solubility
formation of gel layer and the chain entanglement which in these both two. At the end of 1 h, the tablet was
provides higher resistance to the drug release for sufficient withdrawn, soaked with tissue paper, and weighed. Then
period of time. Another synergistic and potentiating effect after every 2 hours, weight gained by the tablets was noted,
contributed by the Aloe Vera is its anti-diabetic effect thus and this process was continued till the end of 12 hours. The
making the drug more patients compliant. Guar gum and percentage weight gain by the tablet was calculated by the
xanthan gum contributes their swelling and gel forming following formula.
properties with the time independent controlled release by
providing surface erosion of matrix. % Swelling index = Mt- Mo /Mo×100
Where, Mt = Wt. of tablet at time “t”.
Swelling index:
Mo = Wt. of tablet at time, t = 0.

Table 3: Formulation composition of matrix tablet (F- 1 to F - 4)

Ingredients name (mg) F-1 F-2 F-3 F-4

Metformin Hydrochloride 40 40 40 40
Guar gum 20 30 - -
Xanthan gum - - 20 30
Methocel K4M - - - -
Aloe Vera - - - -
Polyvinyl pyrrolidone 12.5 12.5 12.5 12.5
Microcrystalline cellulose 60 50 60 50
Talc 50 50 50 50
Aerosil 17.5 17.5 17.5 17.5

Table 4: Formulation composition of matrix tablet (F - 5 to F - 9)

Ingredients name (mg) F-5 F-6 F-7 F-8 F-9
Metformin Hydrochloride 40 40 40 40 40
Guar gum - - 10 10 10
Xanthan gum - - 10 10 10
Methocel K4M 20 30 10 10 10
Aloe Vera - - 50 50.5 60
Polyvinyl pyrrolidone 12.5 12.5 12.5 12.5 12.5
Microcrystalline cellulose 60 50 30 30 30
Talc 50 50 20 20 16
Aerosil 17.5 17.5 17.5 17 11.5

Evaluation of tablets the help of analytical balance, then the average weight was
calculated and finally the comparison of the individual tablet
Post Compression parameters
weights to the average was done. The percentage of weight
Appearance: The tablet must be free from cracks, variation was calculated by applying the following formula.
depressions etc. The color and the polish must be uniform % of wt. variation = Individual wt. –
on the whole surface of tablet. The tablets should be smooth
Average wt. /Average wt. ×100
from all surfaces. [10].
Hardness:
Uniformity of weight
The hardness of the tablet is defined as the load required
Weight variation was carried out to check that whether each
crushing or fracture a tablet placed on its edge. Sometime it
of the tablets contains the proper amount of drug. The test is also termed as tablet crushing strength. The hardness test
was performed by weighing the 20 tablets individually with
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was performed using Monsanto type hardness tester. The rotational speed of 100 rpm at 37±0.5 ºC. The dissolution
crushing strength test was performed on 6 tablets from each media used were 900 mL of pH 6.8 phosphate buffer
formulation. The hardness was measured in terms of kg/cm2 solutions for 12 hrs. Sink condition was maintained for the
[10]. whole experiment. Samples usually 10 ml were withdrawn
at regular intervals of time and the same volume of
Friability:
prewarmed (37±0.5 ºC) fresh dissolution medium was used
For each batch of formulation the friability of 20 tablets was to replace in order to maintain the volume constant. The
determined by using Roche type friabilator. The device samples withdrawn were further evaluated for drug content
subjects to the combined effect of abrasion and shock in a in each sample after suitable dilution with
plastic chamber revolving at a speed of 25 rpm for 4 min and spectrophotometer. These were analyzed at 233nm [13].
dropping the tablets at a height of 6 inch in each revolution.
Total nine formulations of sustained release tablets of
Preweighed sample of tablets were placed in the friabilator
Metformin Hydrochloride were made and composed of
and then subjected to 100 revolutions. following ratios of polymers as given in the tables 5 and 6
Tablet thickness: and their dissolution rate profiles were checked at different
intervals of time. The values of in vitro drug release are
Tablet thickness is particular in reproducing appearance as depicted in the Table 7 and 8.
well as in counting by using filling equipment. Some filling
equipment devices presumes the uniform thickness of the The % of drug release was calculated from the given formula
tablets as a counting mechanism. Ten tablets were taken and Amount of drug release (mg) = (Concentration Dilution
their thickness was recorded using micrometer [11].
factor Volume of dissolution medium)/ 1000
Drug content uniformity:
% drug release = Amount of drug released (mg) 100/ dose
The four tablets from each batch were randomly selected, (mg) [14]
weighed and then crushed in mortar. The powder equivalent
to 10mg were weighed and dissolved in 50 ml methanol,
RESULTS AND DISCUSSION
from this solution 1 ml solution was again diluted to 10 ml Results
with methanol. From this diluted solution was taken and
further diluted up to 10 ml with methanol and assayed for Determination of absorption maxima
drug content at 233 nm using blank as standard solution. The absorption maxima of Metformin Hydrochloride in
In vitro dissolution studies: phosphate buffer of pH was found to be 233.00nm which
successfully resembled with pharmacopoeial standards.
Drug release studies were conducted using USP dissolution
apparatus I, basket type (Electro lab, Mumbai, India) at a

Figure 1: U.V graph showing bell Shaped curve of Metformin Hydrochloride during its calibration.

Figure 2: Absorption maxima of Metformin Hydrochloride.

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Table 5: Standard curve data of metformin hydrochloride in saline phosphate buffer pH (6.8)
Sr. No. Concentration (µg/ml) Absorbance (nm)
1. 1 0.101
2. 2 0.158
3. 3 0.212
4. 4 0.259
5. 5 0.356
6. 6 0.417
7. 7 0.498
8. 8 0.560
9. 9 0.645
10. 10 0.707

Figure 3: Standard curve of Metformin HCl in saline phosphate buffer of pH 6.8.

Table 6: The statistical parameters related to standard curve of metformin hydrochloride in saline phosphate buffer
pH (6.8)
Sr. No. Parameters Values
1. Regression Coefficient 0.995
2. Equation of line 0.069x + 0.0119

As it is clearly depicted from the graph of figure that the value of regression coefficient for Metformin Hydrochloride is 0.995,
which clearly demonstrates and proves the linear analysis of standard curve of drug.

Table 7: Cumulative % drug release of formulations of sustained release tablets (F-1 to F-4).
Time (min.) F-1 F-2 F-3 F-4
0 0 0 0 0
30 12.1 13.4 11.1 9.2
60 26.1 24.10 22.09 38.22
120 48.11 48.12 44.06 40.44
180 60.10 60.16 58.10 52.7
240 78.09 74.32 72.12 64.12
300 88.11 80.56 78.32 72.31
360 92.15 88.55 84.42 84.62
420 94.44 92.22 89.54 88.45
480 94.54 92.21 94.12 92.55
540 94.62 92.50 94.18 92.52
600 94.22 92.26 94.20 92.25
660 94.83 92.33 94.27 92.63
720 94.19 92.44 94.45 94.64

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Table 8: Cumulative % drug release of formulations of sustained release tablets (F-5 to F-9).
Time (min.) F-5 F-6 F-7 F-8 F-9
0 0 0 0 0 0
30 8.4 8.9 6.2 6.3 6.5
60 36.16 25.42 12.40 10.12 10.12
120 40.22 36.55 26.36 23.65 24.12
180 50.21 42.66 38.45 31.36 32.33
240 59.12 55.16 44.48 39.45 39.27
300 70.31 62.18 54.56 48.11 49.62
360 82.44 69.12 66.35 60.32 60.14
420 86.55 78.20 78.75 72.21 70.84
480 91.41 89.22 88.58 79.12 79.45
540 91.22 90.32 94.14 88.66 86.32
600 93.33 94.44 94.55 94.45 96.55
660 94.46 94.45 94.45 94.40 96.68
720 94.47 94.55 94.65 94.44 97.77

Figure 4: In vitro dissolution profiles of Metformin Hydrochloride of batches (F-1 to F-9).

Table 9: Results of precompression parameters of powder blends of Metformin Hydrochloride
Formulations Angle of Bulk density Tapped Carr’s index Hausner’s
repose density ratio
F-1 33.4±0.03 0.415±0.01 0.445±0.04 13.75±0.02 1.161±0.02
F-2 28.8±0.04 0.422±0.02 0.443±0.03 10.44±0.03 1.182±0.02
F-3 29.7±0.04 0.409±0.02 0.451±0.02 13.91±0.02 1.151±0.03
F-4 25.4±0.03 0.318±0.02 0.363±0.07 13.47±0.01 1.189±0.01
F-5 26.4±0.02 0.317±0.01 0.372±0.02 14.45±0.02 1.178±0.02
F-6 33.2±0.02 0.319±0.03 0.370±0.02 13.89±0.02 1.142±0.04
F-7 29.0±0.03 0.320±0.02 0.362±0.03 12.68±0.02 1.168±0.03
F-8 27.8±0.04 0.323±0.02 0.442±0.04 13.46±0.02 1.178±0.03
F-9 26.4±0.02 0.317±0.01 0.365±0.04 14.45±0.01 1.180±0.02

Table 10: Results of Post compression parameters of punched tablets of Metformin Hydrochloride
Formulations Weight variation of Hardness Thickness Friability
tablet (mg) (kg/cm2) (mm) (%)
F-1 202.15±1.73 5.64±0.45 3.42±0.48 0.59
F-2 201.55±1.54 5.58±0.40 3.49±0.15 0.49
F-3 202.0±1.45 5.44±0.36 3.54±0.20 0.78
F-4 201.9±1.65 5.60±0.33 3.48±0.14 0.44
F-5 201.65±1.46 5.63±0.38 3.44±0.15 0.34
F-6 201.6±1.39 5.53±0.31 3.55±0.24 0.69
F-7 201.8±1.70 5.57±0.31 3.58±0.21 0.73
F-8 201.5±1.50 5.49±0.24 3.55±0.23 0.59
F-9 201.65±1.53 5.59±0.29 3.59±0.19 0.44
The post compression parameters of compressed batches was found within acceptable limits as per according U.S.P limits.

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Table 11: Drug content uniformity of tablet batches

Formulations Drug content (%)
F-1 99.7%
F-2 99.41%
F-3 99.48%
F-4 100.12%
F-5 96.50%
F-6 98.79%
F-7 98.84%
F-8 99.79%
F-9 99.93%

Curve fitting analysis of in vitro dissolution studies and Higuchi, Korsmeyer and Peppas models in order to know
the mechanism of drug release from matrix of tablet which is
The dissolution data obtained for best F-9 formulation was usually made of hydrophilic polymers. The results are shown
fitted to various kinetic models like Zero order, First order,
below.

Table 12: Zero order kinetics of F-9 formulation

Sr. No. Time % Cumulative drug release
1). 0 0
2). 30 6.5
3). 60 10.12
4). 120 24.12
5). 180 32.33
6). 240 39.27
7). 300 49.62
8). 360 60.14
9). 420 70.84
10). 480 79.45
11). 540 86.32
12). 600 96.55
13). 660 96.68
14). 720 97.77

Figure 5: Graph of Zero order kinetics of best formulation of F-9.

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Table 13: First order kinetics of F-9 formulation

Sr. No. Time (min.) Log % cumulative drug retained
1). 0 2
2). 30 1.970
3). 60 1.953
4). 120 1.880
5). 180 1.830
6). 240 1.783
7). 300 1.702
8). 360 1.600
9). 420 1.464
10). 480 1.312
11). 540 1.136
12). 600 0.537
13). 660 0.521
14). 720 0.348

Log% cumulative drug retained was calculated by subtracting the cumulative drug release from 100 and then taking the
logarithm of obtained value.

Figure 6: Graph of First order kinetics of F-9.

Table 14: Higuchi kinetics of F-9 formulation

Sr. No. Square root of time % Cumulative drug release
1). 0 0
2). 5.477 6.5
3). 7.745 10.12
4). 10.954 24.12
5). 13.416 32.33
6). 15.491 39.27
7). 17.320 49.62
8). 18.973 60.14
9). 20.493 70.84
10). 21.908 79.45
11). 23.237 86.32
12). 24.494 96.55
13). 25.690 96.68
14). 26.832 97.77

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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(3-s):374-385

Figure 7: Graph of Higuchi kinetics of F-9.

As the regression coefficient values for Zero order and First concentration gradient increases, the drug is released and
order were found to be 0.98 and 0.89 with high linearity and the distance for diffusion gradually increases finally the drug
release of drug from matrix made of hydrophilic polymers diffuses at a comparatively slower rate as the distance for
involves the factors of diffusion. Diffusion is related to diffusion increases. This phenomenon is preferred to as
transport of drug from a matrix into the in vitro study fluid, square root kinetics or Higuchi kinetics.
which in turn depends on the concentration. As the

Table 15: Korsmeyer and Peppas kinetics of F-9 formulation

Sr. No. Log time Log % Cumulative drug release
1). 0 0
2). 1.477 0.812
3). 1.788 1.005
4). 2.079 1.382
5). 2.255 1.509
6). 2.380 1.594
7). 2.477 1.695
8). 2.556 1.779
9). 2.623 1.850
10). 2.681 1.900
11). 2.732 1.936
12). 2.778 1.984
13). 2.819 1.985
14). 2.857 1.990

Figure 8: Graph of Korsmeyer Peppas of F-9 formulation.

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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(3-s):374-385

Results of flow properties of Aloe barbadensis powder compared to others. The cumulative % drug release was also
found to be maximum in the 12 hours with this formulation
The viscosity of 1% gum solution in water was found to be i.e. 97.77%. Due to the complete release of drug within 12
8.54 poise indicating viscous flow of gel. But the gum was hours the effect of the drug can be seen throughout the day,
made to dry with the help of tray dryer, and the powder was thus eliminating the intake of another dose of drug in the
obtained.
same day. F-9 formulation composition also served to be
Table 16: Flow properties of Aloe barbadensis powder very effective as it contains high ratio of Aloe barbadensis i.e.
1:2 (60mg) while all other used polymers ratio was kept
Sr. No. Parameters Value constant throughout the process.
1). Bulk density (g/ml) 0.35
The regression coefficient “r” value of zero order and first
2). Tapped density (g/ml 0.39
order were 0.982 and 0.894. The regression coefficient “r”
3). Carr’s index (%) 13.17
value for Higuchi and Korsmeyer and Peppas were found to
4). Hausner’s ratio 1.13 be 0.95 and 0.98. It indicated that the release of drug from
5). Angle of repose 23° these sustained formulations was governed by diffusion
controlled process. The value of “n” was found to be 0.742
indicating the anomalous non Fickian diffusion as it is
After seeing the in vitro release data of all formulation
depicted from the Korsmeyer and Peppas model graph of
batches it was demonstrated that the F-9 was considered as
figure 8. The “n” is responsible for depicting the type of
the best formulation because it was capable to release the
diffusion.
drug in the sustained manner with respect to time as

Stability studies
Table 17: Accelerated stability study of matrix tablets of Metformin HCl of batch F-9 at 40°C and 75% Relative
humidity.
Sr. No. Parameter Initial 1 month 2 month 3 month
1). Average weight (mg) 201.65 201.67 201.69 201.69
2). Friability (%) 0.44 0.43 0.43 0.43
3). Hardness (Kg/cm2) 5.59±0.29 5.49±0.29 5.49±0.29 5.40±0.01
4). %Drug release (up to 12 hours) 97.77 97.62 97.62 97.62

The stability study on the final and best formulation F-9 indicated that there was slight acceptable differences in average
weight, friability, hardness and in vitro drug dissolution after 3 months at 40°C/75% RH [8].
Swelling index

Figure 9: Graph of swelling index of formulations F-1 to F-9.

DISCUSSION polymeric chains. Thus F-9 formulations which consist of

highest ratio of Aloe barbadensis with the combination of
In the matrix tablet, Xanthan gum, Guar gum, Aloe other three polymers provides sustained release of drug
barbadensis and Methocel K4M were used as retarding with 6.5% of drug release within 1 hour and finally 97.7% of
agent. And the study showed that Aloe barbadensis drug release within 12 hours, maximum for therapeutic
satisfactorily proved to be best pharmaceutical excipient in effect to occur. The combinational composition of
the formulation and manufacture of sustained release matrix hydrophilic polymers provides the formation of original
tablets because of its high viscosity and capability to form a protective gel layer which controls the penetration of water
gelatinous layer around tablet core. The dried mucilage was into the tablet. As the outer gel layer fully hydrates and
capable to undergo sufficient swelling and entanglement of
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Sharma et al Journal of Drug Delivery & Therapeutics. 2019; 9(3-s):374-385
dissolves, consequently a new inner layer must replace it CONFLICT OF INTEREST
and be cohesive as well as continuous enough to retard the
influx of water and control of drug diffusion. Aloe A special vote of thanks as a token of helping hands was
barbadensis was chosen to be best fit polymer or natural given to co- authors. But during the submission of this
gum because of its excellent anti-diabetic effect which manuscript, not any kind of financial or personal help was
combats all the side effects of Metformin such as G.I.T taken. During the research work, it was kept in mind that
symptoms and thus provides synergistic action to drug. nobody intentions are disturbed. Thus after the publication
of this research work, not any kind of conflict of interest will
CONCLUSION be seen at any step. As this research work is of my keen
interest, hard work and efforts.
Metformin Hydrochloride is used as an anti-diabetic drug. In
the present research work the sustained release tablet was REFERENCES
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