Research and evaluation of Glimepiride Sustained release tablet
formulation
Nishigandha Kharde*, Pratik Bhanage, Megha Salve
Department of pharmacy,
Shivajirao pawar college of pharmacy pachegaon 413721.
Abstract:
The purpose of this effort is to construct a sustained release formulation of
glimepiride, which is currently used to treat type 2 diabetes mellitus, and to
examine how polymers affect the drug's release profile. The main goal of this
project was to use the polymer ethyl cellulose to create a sustained release
anti-diabetic pill. Using this polymer, wet granulation was used to produce
sustained release glimepiride tablets in multiple trials with varying polymer
concentrations. Pre-compression characteristics such as bulk density, tapped
density, angle of repose, Hausner's ratio, and compressibility ratio were
assessed for the prepared granules. Numerous physical parameter tests,
such as those for weight variation, friability, hardness, thickness, and
diameter, were performed on the produced tablets.
Keywords: Glimepiride, Sustained release tablet, Diabetes mellitus, Wet
granulation method
Introduction:
The creation of oral sustained release formulations aims to regulate drug
release from the gastrointestinal tract (GIT) and preserve a long-term,
efficient drug concentration in the systemic circulation. Such a medication
will remain in the stomach following oral administration, eventually releasing
the medication in a regulated fashion to allow for continuous delivery of the
medication to the GIT’s absorption sites [1,2]. Reduced effectiveness of the
administered dose results from partial drug release from the dosage form in
the absorption zone.[3] The purpose of sustained release dosage type is to
preserve therapeutic blood or tissue levels of the medicine over a extended
duration.[4]
A person with diabetes mellitus has excessive blood sugar
levels, which can be caused by either insufficient insulin production by the
body or improper cell response to the insulin generated. The pancreas
produces the hormone insulin, which allows body cells to absorb glucose and
convert it into energy. The accumulation of glucose in the blood can result in
vascular, nerve, and other issues if the body cells are unable to absorb it .
According to recent estimates, there were 171 million diabetics worldwide in
2000; by 2030, that number is expected to rise to 366 million.[5] The main
characteristic of diabetes is the degree of hyperglycemia that Increases the
risk of microvascular damage, including retinopathy, nephropathy, and
neuropathy. It is linked to a lower life expectancy, substantial morbidity from
certain microvascular consequences of diabetes, a higher risk of
macrovascular complications (stroke, ischemic heart disease, and peripheral
vascular disease), and a lower quality of life. According to the American
Diabetes Association (ADA), the national costs of diabetes in the United
States were projected to reach US$132 billion in 2002 and US$192 billion in
2020.[6]
Glimepiride is a third-generation sulphonylurea class
oral blood glucose-lowering medication that is now prescribed to treat
hyperglycemia in non-insulin-dependent diabetic mellitus (NIDDM). The
biopharmaceutical classification system places glimepiride in class II.[7] The
medication has a high permeability but is insoluble in water and an acidic
environment. Oral bioavailability is almost 100%, and oral absorption is
consistent and quick. Sustained release formulations, which are to be given
once day for blood glucose monitoring, are supported by the
pharmacokinetics and dose schedule, improving patient compliance and
efficacy. The half-life is roughly five hours, and 99.5% of plasma proteins
bind.[8] . The metabolic and endocrine disorder known as diabetes mellitus
(DM) is typified by elevated triglyceridemia, cholesterol, and glucose levels.
Diabetes mellitus affects about 200 million individuals globally and is brought
on by either defects in insulin secretion, inadequate insulin secretion, or
both. The hormone insulin, which is produced by the pancreas, facilitates the
body's cells' absorption of glucose. If the cells are unable to absorb glucose
from the body, it can result in serious consequences. [8,9].
1-[[p-[2-(3-ethyl-4-methyl-2-oxo-3-Pyrroline-
1carboxamido) ethyl] phenyl] sulfonyl]-3-(trans-4-methylcyclohexyl) urea is
the chemical name of Glimepiride.[10].It increases the amount of insulin
secreted by the pancreatic β-cells by depolarizing the cell membrane and
blocking potassium channels, which triggers the start of metabolic activities
that produce insulin . The predicted water solubility of glimepiride, an off-
white or white crystalline powder, is 1.6 µg/ml (pKa=6.2), yet it is
comparatively insoluble in water. This results in significant fluctuations in its
bioavailability [11,12].Additionally, the excipients may interact with the
medicine and change its dissolving properties while it is being stored.
Numerous publications indicate significant aging-related changes that
negatively impact oral sulphonylurea medication solubility and,
consequently, bioavailability [8, 9]. A number of strategies have been
employed to get around these issues, including the creation of a complex
between glimepiride and β-CD, hydroxylpropyl-β-CD, or sulfobutylether-β-CD
in the presence and absence of various water-soluble polymers.[11,13].
Material and Method:
Pre formulation studies –
Angel of repose:
Both the fixed funnel and freestanding cone
approaches use a funnel with its tip fixed at a specific height, h,
maintained 2 cm above graph paper that is positioned on a level
horizontal surface. Where r is the radius of the conical pile’s
base ,angle of repose can be calculated using the following formula
¢= tan-1 (h/r)
Where, ¢ is the angle of repose,
h is the pile's height, r is the pile's base radius.
Bulk density and Tapped density
The tapped bulk density as well as the loose bulk density
were calculated. Two grams of granules from each recipe were added
to a 10-milliliter measuring cylinder after being lightly shaken to break
up any agglomerates that might have formed. The cylinder was
allowed to descend its own weight from the hard surface at intervals of
two seconds from a height of 2.5 cm in order to observe the initial
volume. The tapping was kept up till the loudness didn't change any
more.
The following formulas were used to determine LBD and TBD.
LBD: Powder weight divided by packing volume.
TBD: Powder weight divided by the packing's taped capacity.
Carr’s index:
Carr’s index=(TBD-LBD) * 100 / TBD
where ,LBD: is the powder’s weight divided by the packing
volume.
TBD: Powder weight divided by the packing’s taped
capacity.
Hausner’s ratio:
The following formula can be used to calculate Hausner's ratio.
Hausner's ratio = TBD / LBD
Where, LBD stands for loose bulk densities and TBD for tapered bul
densities.[6,14].
Formulation:
The matrix tablets were created using the wet granulation process. With the
use of the granulating agent PVP K-30, the medication, Ethyl cellulose and
microcrystalline cellulose were combined and granulated. After that, the
moist substance was dried in an oven set to 50˚C after passing through sieve
number 44. Granules are sieved using sieve number 22 after drying. Talc and
magnesium stearate were used to lubricate the grains. After that, a tablet
punching machine was used to compress the tablets.[15,16]
Table-1: Formulation of Glimepiride sustained release tablet
F1 F2 F3 F4 F5
Glimepiride 5 5 5 5 5
Ethyl cellulose 15 20 25 30 35
Microcrystallin 52 47 42 37 32
e cellulose
Povidone k-30 20 20 20 20 20
Magnesium 5 5 5 5 5
stearate
Talc 3 3 3 3 3
Total 100 100 100 100 100
Evaluation of formulated tablet:
[Link] variation:
At first, each of the twenty tablets was weighed separately. The standard
deviation is determined after calculating the average weight of the tablets.
[Link]:
Density Vernier callipers (20 tabs) were used to measure each tablet’s
thickness.[8].
3. Hardness :
Hardness test Using a Monsanto Hardness tester, the tablets’ hardness was
assessed. Kg/cm2 is the unit of measurement. The mean and standard
deviation values were computed after six tablets were chosen at random
from each formulation.[6].
[Link]:
Twenty tablets were first weighed, put in the Roche friability device, and
rotated for four minutes at 25 rpm. The tablets were cleaned and weighed
once more following the revolutions. % Friability = {(Initial weight-Final
weight)/Initial weight} x 100 was the formula used to measure it.[8].
[Link] vitro dissolution study:
Glimepiride sustained release tablet dissolution studies were conducted
using Hermann et al. (2005) methodology. Using phosphate buffer with a pH
of 6.8, the experiment was conducted using the USP apparatus 2 (paddle
method) for eight hours at 50 rpm and 37º ± 0.5 °C. Using a UV
spectrophotometer, released drug samples from the dissolution medium
were measured at 228 nm.[1,17].
Result and Discussion:
Compatibility study using FTIR analysis:
None of the drug glimepiride's peaks appear or vanish in the physically
mixed mixture. The slight variation in transmittance percentage could be the
result of crystalline alteration. Thus, it demonstrates that the medication and
polymer do not interact chemically.
Fig.1: FTIR spectra of glimepiride drug
Table:2 Pre formulation study of glimepiride
Formulati Angle of Bulk Tapped Hausner’s Car’s
on Repose (°) Density Density ratio index
(g/ml) (g/ml) (%)
F1 29.74 0.465 0.540 1.17 14.8
F2 31.21 0.476 0.526 1.11 10.6
F3 29.054 0.444 0.555 1.26 20.72
F4 28.39 0.487 0.571 1.18 15.93
F5 30.46 0.454 0.512 1.13 12.10
Table -3 : Evaluation of prepared glimepiride sustained release
tablet formulation
Formulation Weight Hardness Thickness Friability
variation (kg/cm²) (mm)
(mg)
F1 99.8±0.91 3.34±0.10 2.07±0.06 0.40±0.08
F2 100.2±0.82 4.00±0.55 2.09±0.08 0.35±0.10
F3 100.1±0.12 3.20±0.40 2.11±0.07 0.24±0.12
F4 101.4±0.72 3.80±0.20 2.12±0.06 0.16±0.06
F5 99.3±0.58 4.05±0.20 2.16±0.11 0.27±0.15
Conclusion:
The Glimepiride Sustained Release Tablet formulation offers a promising
approach for managing type 2 diabetes. By providing a sustained release of
Glimepiride over an extended period, these tablets can:
1. Improve patient compliance by reducing dosing frequency.
2. Enhance glycemic control by maintaining therapeutic drug levels.
3. Potentially reduce side effects associated with peak plasma
concentrations.
The formulation’s success depends on optimizing the polymer blend,
granulation process, and tablet compression parameters. Further studies,
including in vivo evaluations, are necessary to confirm the formulation’s
efficacy and safety. Overall, the Glimepiride Sustained Release Tablets have
the potential to provide a more convenient and effective treatment option for
patients with type 2 diabetes.
Acknowledgement:
The authors would like express to thankful to our Teacher Dr. Salve mam and
prof. Pratik Bhanage sir for their Guidance and support for this research
article. Special thanks to Prof. Chopade sir for guidance.
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