Aegle Marmelos - Excipient2
Aegle Marmelos - Excipient2
Aegle Marmelos - Excipient2
Abstract
The objective of the current research study was to formulate and evaluate a sustained-release linezolid tablet using
the natural antibacterial polymer Aegle marmelos. The natural gum of Aegle marmelos is becoming increasingly
used in pharmaceutical formulations as a beneficial medication with excipients. Natural-based plant materials
are biocompatible, free of side effects, biodegradable, and economic. Therefore, in order to maintain the drug
releases from the matrix system, Aegle marmelos fruit gum as a natural polymer and HPMC grade (K100M) as a
synthetic polymer were used in the formulation of the linezolid matrix tablet. The formulation of sustained-release
matrix tablets included the wet granulation technique. The formulated matrix tablets were evaluated in terms of
weight variation, hardness, diameter, physical appearance, friability, thickness, and in vitro drug release. Each
formulation’s matrix tablet passed the required physical assessment tests. The formulation analyses of the tablets’
dissolution showed sustained releases of drugs for up to 10–12 hours. Additionally, several polymer combinations
and fillers were used to improve drug release factors using the 32 factorial design approach, drug release kinetics
were optimized, and the antibacterial study was evaluated.
Keywords: Aegle marmelos, Fruit Gum, HPMC K100M, Linezolid, Sustained Release
Article Received on: 21.10.2022 Revised on: 18.01.2023 Accepted on: 03.02.2023
192 Formulation and Evaluation of Sustained Release Linezolid Tablet using Natural Antibacterial Polymer...
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194 Formulation and Evaluation of Sustained Release Linezolid Tablet using Natural Antibacterial Polymer...
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196 Formulation and Evaluation of Sustained Release Linezolid Tablet using Natural Antibacterial Polymer...
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Where Q is the amount of drug released in time t per Table 4. T axonomical classification of Aegle
unit area A, marmelos gum
C is the drug initial concentration,
Kingdom Plantae
Cs is the drug solubility in the matrix media and
Subfamily Aurantioideae
D is the diffusivity of the drug molecules (diffusion
coefficient) in the matrix substance. The data obtained Order Sapindales
were plotted as cumulative percentage drug release versus Family Rutaceae
square root of time28. Genus A. marmelos
Species Aegle species
2.2.9.4 Korsmeyer-Peppas Model Tribe Clauseneae
To find out the mechanism of drug release, the first 60%
of drug release data were fitted in the Korsmeyer-Peppas Table 5. P
hysical characterization of Aegle marmelos
mode of the equation (4): fruit gum
Mt Parameters Observation of gum
Kt n (4)
M Color Yellowish brown
Where Mt/M∞ is a fraction of the drug released at Odour Characteristic
time t, Taste Characteristic
k is the release rate constant and Nature Amorphous
n is the release exponent.
The n value is used to characterize different releases Table 6. P
hytochemical characterization of Aegle
for cylindrical-shaped matrices28. marmelos fruit gum
Test Observed gum
2.2.10 Antibacterial Study (Zone of Inhibition) Carbohydrates Present
Mueller–Hinton agar plates were used for the test. Glycoside Absent
After pouring approximately 20 ml of molten agar Tannins Absent
media into sterile Petri dishes, the agar plates were
Saponins Absent
allowed to solidify under a laminar flow hood. It had
Protein Present
been demonstrated with 105 organisms/ml suspensions
of each strain of Methicillin-Resistant Staphylococcus Gum Present
aureus (MRSA). The inoculum of these cultures was Polysaccharide’s Present
spread on the surface of the agar plates. Plates were
allowed to air dry for 10 minutes. After creating a zone Table 7. Flow properties of Aegle marmelos fruit gum
in each plate, pouring the drug on it, and placing it Parameter Observed gum
in the incubator at 37.8°C for 24 hours, the zones of
pH (1% w/v solution) 6.4
inhibition (diameter in mm) are measured on the agar
Swelling index 16.8%
surface with a scale29.
Bluk density 0.47 ± 0.01 (g/cm3)
Tapped density 0.56 ± 0. 01
3. Results and Discussion Hausner’s ratio 1.19 ± 0. 006
3.1 Gum Characterization Carr’s index 16.23 ± 0. 44
It is based on the taxonomy of Aegle marmelos, which The physicochemical properties and micromeritics
is classified as belonging to the Kingdom of Plantae, properties of gums were performed as per the procedure.
Order of Sapindales, and family Rutaceae. The detailed It was observed that gum was acidic in nature but they
classifications were shown in Table 4. Characterization are near neutral. Information on the pH of polymers is an
and flow properties are shown in Tables 5, 6 and 7. important parameter in determining their appropriateness
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198 Formulation and Evaluation of Sustained Release Linezolid Tablet using Natural Antibacterial Polymer...
in formulations, while the stability and physiological Sr. No. Concentration (ug/ml) Absorbance
action of most preparations are influenced by pH. The pH 6 12 0.693±0.0012
of the 1% w/v test solution of gum in water was 6.4. The
7 14 0.792±0.0012
neutral pH suggested that when it was used in uncoated
8 16 0.923±0.0012
tablets, it may be less irritating to the GI tract. It may find
beneficial application in the formulation of acidic, basic Calibration curve,
and neutral drugs. Aegle marmelos (16.8)% gum has a Correlation Coefficient (R²) = 0.999
good swelling index. The gum had a high swelling index, Where y = Absorbance X = Concentration (ug/ml)
suggesting that the gums may perform well as matrixing
agent. Tapped density and bulk density of gum were
found to be 0.47 ± 0.01 and 0.56 ± 0.01, respectively, and
results of Hausner’s ratio, angle of repose, and Carr’s index
showed passable flow properties of gum powder.
Figure 3. FTIR spectra of Aegle marmelos gum. Sr. No. Concentration (ug/ml) Absorbance
1 2 0.309±0.0012
Table 8. Wave number of Aegle marmelos gum
2 4 0.385±0.0016
Sr. No. Functional group present Wave numbers (cm–1) 3 6 0.466±0.0012
of gum
4 8 0.537±0.0008
1 OH – Stretching 3362.05
5 10 0.616±0.0016
2 C-H Stretching 2931.58
6 12 0.686±0.0016
3 C=O Stretching 1746.86
7 14 0.777±0.0012
4 C-O Stretching 1673.69
8 16 0.905±0.0012
5 C-C Deformation 1421.25
9 18 0.984±0.0012
6 Secondary OH 1022.75
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The regression coefficient value was found to be 0.999 3.1.4 Factorial Design Formulations of Linezolid
and the line equation was y = 0.057x + 0.00 for HCL and y Sustained Release Matrix Tablet (Figure 6,
= 0.041x + 0.208, R² = 0.993 for a buffer, R2 value of drug Tables 11, 12 and 13)
showed linearity of the standard curve (Figure 5, Table 10).
Table 13. Results of in vitro dissolution study of factorial design batch F1-F9
Time (Hours) F1 F2 F3 F4 F5 F6 F7 F8 F9
0 0 0 0 0 0 0 0 0 0
1 7.95 8.06 8.18 7.92 7.96 7.59 8.03 9.45 8.02
2 19.82 18.75 20.95 19.82 17.78 20.36 18.75 22.75 31.75
3 22.97 22.09 27.45 22.97 31.32 32.02 35.39 26.54 39.48
4 33.56 36.55 35.69 33.58 39.49 42.45 36.52 36.25 48.36
5 40.35 39.54 39.46 40.58 48.35 49.88 45.62 46.15 56.45
6 47.45 46.48 46.83 47.45 56.45 58.45 55.38 50.66 67.78
7 53.65 52.68 58.45 53.65 67.88 69.55 56.55 58.23 73.26
8 65.26 66.49 63.68 65.26 73.28 75.95 67.96 68.36 78.76
(Continued )
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Figure 7. C
ontour plot for the effect of concentration of gum (X1) and concentration of polymer (X2) on the hardness.
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• Response 2 - % CDR
Figure 8. Contour plot for effect of gum (X1) and amount of HPMC K100M (X2) on % cumulative drug release at 10-12 hrs.
Figure 9. Overlay plot showing the combined effect of Aegle marmelos gum (X1) and polymer (X2).
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The mechanism of drug release from the sustained- the release of drug from matrix tablets of Aegle marmelos
release matrix tablet, formulations were subjected to gum contained tablets fitted best into zero-order kinetics
modelling and drug release kinetic studies such as with maximum values of R2 = 0.9972 and a n value of 1.15.
zero-order, first-order, the Higuchi model, and the It was revealed that the mechanism of drug release was
Korsmeyer–Peppas model. The value of the Regression a super case-II transport, indicating the drug release rate
coefficient (R2) from the drug release kinetic model was does not change over time and the release is attributed to
tabulated. The result of the modelling study revealed that zero-order.
(a) (b) (C)
Figure 11. Zone of inhibition (a) Linezolid, (b) AMG, (c) Formulation.
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Shrey Patel and Rupal Jani 203
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