formulation and evaluation of pulsincap drug …
TRANSCRIPT
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FORMULATION AND EVALUATION OF PULSINCAP DRUG
DELIVERY SYSTEM OF NICORANDIL
*A. Sambasivarao, M.S, Ph.D, T. Jyotshna, S. K. Nishma, P. Lakshmi, Y. Shashank
Professor, A.S.N College of Pharmacy, Burripalem Road, Tenali, A.P India.
ABSTRACT
The present study was aimed to develop the formulation of pulsincap
drug delivery system of Nicorandil. In this study Nicorandil immediate
release granules were prepared by wet granulation method. F9 was
selected as a better formulation to do the further process. In this study
100mg of hydrogel plug was prepared using HPMC K200M by wet
granulation method using 5%w/v PVP K30 solution. Plug 3 was
selected as a better formulation when compared to other formulations.
FTIR studies has shown no interaction between polymer and drug.
Cross-linked gelatine capsule were evaluated and confirmed that 24 hrs
formaldehyde treatment was sufficient. 100mg hydrogel plug was optimized. The results
indicated that drug content was uniform. In-vitro release studies revealed that increasing the
polymer content resulted in sustained release. Value of n in Korsmeyer-Peppas Equation is
greater than 0.89 hence, formulation were follows swelling controlled super case II transport.
KEYWORDS: Pulsincap, Nicorandil, HPMC K200M.
INTRODUCTION
Nicorandil is an orally efficacious vasodilatory drug and antianginal agent. It is a niacinamide
derivative that induces vasodilation of arterioles and large coronary arteries by activating
potassium channels. It is often used for patients with angina who remain symptomatic despite
optimal treatment ith other antianginal drugs.[1]
Nicorandil is a dual-action potassium channel
opener that relaxes vascular smooth muscle through membrane hyperpolarization via
increased transmembrane potassium conductance and increased intracellular concentration of
cyclic GMP. It is shown to dilate normal and stenotic coronary arteries and reduces both
ventricular preload and afterload.[2]
Pulsatile drug delivery systems are time-controlled drug
delivery system. These systems are design to achieve time specific and site specific delivery
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 9, Issue 4, 561-581 Research Article ISSN 2278 – 4357
*Corresponding Author
Dr. A. Sambasivarao
Professor, A.S.N College of
Pharmacy, Burripalem Road,
Tenali, A.P India.
Article Received on
22 Jan. 2020,
Revised on 12 Feb. 2020,
Accepted on 04 March 2020
DOI: 10.20959/wjpps20204-15734
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of drugs according to the circadian rhythm of the body. Pulsatile release pattern has gained
most popular form of controlled drug delivery system because conventional systems with a
continuous release are not ideal. Pulsatile systems are beneficial for the drugs having
chronopharmacological behaviour.[3,4]
The potential benefits of pulsatile drug delivery have
been demonstrated in the management of a number of diseases. PDDS is likely to be
successful for diseases such as asthma, myocardial infarction, angina pectoris, peptic ulcer,
arthritis, hypertension, hypercholesterolemia as in these diseases particular rhythms in the
onset and extent of symptoms are observed.[5]
Cardiovascular diseases such as hypertension
and angina, or chest pain, also follow a definite circadian rhythm. Hypertension is increased
in the early morning hours. Systolic blood pressure rises approximately 3 mm Hg/hr for the
first 4-6 hours post-awakening, while the rate of rise of diastolic blood pressure is
approximately 2 mm Hg/hr. The silent ischemic events showed a circadian pattern with a
high density of 34% events occurring between 6 a.m. and noon.[6]
The causes for these
findings have been suggested to be release of catecholamine, cortisol increase in the platelet
aggregation and vascular tone.
MATERIAL AND METHODS
Materials
Nicorandil, SSG, CCS and CP were obtained as a gift sample from Pharmatrain, Hyderabad,
India. HPMC K200M, MCC, Mannitol, Talc and Mg.Stearate was gift sample from Sunlife
sciences, Hyderabad. All other reagents and solvents used were of analytical grade satisfying
pharmacopoeias specifications.
I. Standard Calibration Curve of Nicorandil 0.1N Hcl buffer
Working standard: 50mg of Nicorandil was weighed and dissolved in 5ml methanol and
then make up to a volume of 50ml with water it gives 1000µg/ml concentrated stock solution.
Dilution 1: From the working standard solution 1ml was diluted to 10ml with 0.1N HCL it
will give 100µg/ml concentrated solution.
From dilution-1, take 0.2, 0.4, 0.6, 0.8 and 1.0ml of solution and was diluted up to mark in
10ml volumetric flask to obtain 2, 4, 6, 8 and 10µg/ml concentrated solutions. The
absorbance was measured in the UV-Visible spectrophotometer at 262 nm using 0.1N Hcl
buffer as blank and graph of concentration versus absorbance was plotted.
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II. Standard Calibration Curve of Nicorandil in 6.8phosphate buffer
Working standard: 50mg of Nicorandil was weighed and dissolved in 5ml methanol and
then make up to a volume of 50ml with water it gives 1000µg/ml concentrated stock solution.
Dilution 1: From the working standard solution 1ml was diluted to 10ml with 6.8 phosphate
buffer it will give 100µg/ml concentrated solution.
From dilution-1, take 0.2, 0.4, 0.6, 0.8 and 1.0ml of solution and was diluted up to mark in
10ml volumetric flask to obtain 2, 4, 6, 8 and 10µg/ml concentrated solutions. The
absorbance was measured in the UV-Visible spectrophotometer at 262 nm using
6.8phosphate buffer as blank and graph of concentration versus absorbance was plotted.
III. Preparation of Cross-Linked Gelatine Capsules
Formalin treatment has been employed to modify the solubility of gelatine capsules.
Exposure to formalin vapours results in an unpredictable decreases in solubility of gelatine
owing to the crosslinkage of the amino group in the gelatine molecular chain aldehyde group
of formaldehyde by Schiff’s base condensation.
Method
Hard gelatine capsule of size 0 was taken. Bodies were separated from cap, 25 ml of 15%
(v/v) formaldehyde was taken into desiccators and a pinch of potassium permanganate was
added to it, to generate formalin vapours. The wire mesh containing the empty bodies of
capsule was then exposed to formaldehyde vapours. The caps were not exposed leaving them
water-soluble. The desiccators were tightly closed. The reaction was carried out for 12 h after
which the bodies were removed and dried at 500C for 30 min to ensure completion of reaction
between gelatine and formaldehyde vapours. The bodies were then dried at room temperature
to facilitate removal of residual formaldehyde. These capsule bodies were capped with
untreated caps and stored in a polythene bag.
Preparation of hydrogel plug
Hydrogel plug was prepared by wet granulation method by using 5% w/v PVP K30 solution.
Preparation of binder solution: Accurately weigh 5gms of PVP K30 and dissolve in 100ml
of water.
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Ingredients Plug 1 Plug 2 Plug 3
HPMC K200M 20 40 60
MCC 80 60 40
Total weight 100 100 100
The formulation of pulsincap hydrogel plug was prepared by using wet granulation method
with PVP K30 solution in different proportions of HPMC K200M using 6mm punches and
dies on rotary tablet press keeping variation in thickness and hardness values of tablet plug.
This plug was then fitted into the body of hard gelatin capsule (containing equivalent to 10mg
of Nicorandil granules) which was cross linked by exposing the capsule bodies to
formaldehyde vapour in desiccator for 12 hours.
IV. Preparation of Immediate release Nicorandil granules
All the excipients except Magnesium stearate & Aerosil were cosifted through # 40 sieve
& blended in a poly bag for 10 min
Preparing the dump mass using 5% w/v PVP K30 solution
Wet screening the dampened powder into granules using # 20 sieve
To the above mixture # 60 sieve passed Magnesium stearate & Aerosil were added &
lubricated by blending in a poly bag for 5 min
Table 1: Formulation for Nicorandil Immediate release granules.
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Nicorandil 10 10 10 10 10 10 10 10 10
SSG 1 2 3 -- -- -- -- -- --
CCS -- -- -- 1 2 3 -- -- --
Crospovidone -- -- -- -- -- -- 1 2 3
MCC 52 51 50 52 51 50 52 51 50
Mannitol 35 35 35 35 35 35 35 35 35
Mg.stearate 1 1 1 1 1 1 1 1 1
Talc 1 1 1 1 1 1 1 1 1
Total weight 100 100 100 100 100 100 100 100 100
III. EVALUATION OF GRANULES
The formulated granules were evaluated for the following quality control studies and
dissolution studies.
1. Density
a) Bulk density (BD): It is the ratio of total mass of powder to the bulk volume of powder
Weigh accurately 25 g of granules, which was previously passed through 22sieve and
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transferred in 100 ml graduated cylinder. Carefully level the powder without compacting, and
read the unsettled apparent volume. Calculate the apparent bulk density in gm/ml by the
following formula.
Bulk density = weight of powder/ Bulk volume.
Db =
0V
M
M = mass of the powder, V0 = bulk volume of the powder.
b) Tapped density (TD): It is the ratio of total mass of powder to the tapped volume of
powder.
Weigh accurately 25 g of granules, which was previously passed through 22# sieve and
transferred in 100 ml graduated cylinder of tap density tester which was operated for fixed
number of taps until the powder bed volume has reached a minimum, thus was calculated by
formula.
Tapped density = Weigh of powder / Tapped volume
Dt = (M) / (V f).
M = mass of the powder, V f = tapped volume of the powder.
2. Carr‟s Index
Compressibility index of the powder blend was determined by Carr’s compressibility index.
It is a simple test to evaluate the BD and TD of a powder and the rate at which it packed
down.[19]
The formula for Carr’s index is as below:
Compressibility index = 100 x density Tapped
density Bulk -density Tapped
3. Hausner‟s Ratio
Hausner’s Ratio is a number that is correlated to the flow ability of a powder.
Hausner‟s Ratio = DensityBulk
Density Tapped
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Table 2: Compressibility index limits.
Scale of Flow ability (USP29-NF34)
Compressibility Index (%) Flow Character Hausner‟s Ratio
≤ 10 Excellent 1.00-1.11
11-15 Good 1.12-1.18
16-20 Fair 1.19-1.25
21-25 Passable 1.26-1.34
26-31 Poor 1.35-1.45
32-37 Very Poor 1.46-1.59
> 38 Very, very Poor > 1.60
4. Angle of Repose: It is defined as the maximum angle possible between the surface of a
pile of powder and the horizontal plane.
Angle of Repose of granules was determined by the funnel method. Accurately weighed
powder blend was taken in the funnel. Height of the funnel was adjusted in such a way the tip
of the funnel just touched the apex of the powder blend. Powder blend was allowed to flow
through the funnel freely on to the surface. Diameter of the powder cone was measured and
angle of repose was calculated using the following equation.
= tan-1
(h/r)
Where: = angle of repose, h = height in cms, r = radius in cms.
The angle of repose has been used to characterize the flow properties of solids. It is a
characteristic related to inter particulate friction or resistance to movement between particles.
Table 3: Angle of repose limits.
Flow Properties and Corresponding Angles of Repose
Flow Property Angle of Repose (degrees)
Excellent 25–30
Good 31–35
Fair—aid not needed 36–40
Passable—may hang up 41–45
Poor—must agitate, vibrate 46–55
Very poor 56–65
Very, very poor >66
B) Post compression studies
1. Average weight/Weight Variation: 20 tablets were selected and weighed collectively and
individually. From the collective weight, average weight was calculated. Each tablet weight
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was then compared with average weight to assure whether it was within permissible limits or
not. Not more than two of the individual weights deviated from the average weight by more
than 7.5% for 300 mg tablets and none by more than double that percentage.
Average weight = weight of 20 tablets
20
%weight variation = average weight - weight of each tablet ×100
Average weight
Table 4: Weight variation tolerance for uncoated tablets.
Acceptance criteria for tablet weight variation (USP 29-NF 34)
Average weight of tablet(mg) % difference allowed
130 or Less than ± 10
130-324 ± 7.5
More than 324 ± 5
2. Thickness: Thickness of the tablets (n=3) was determined using a Vernier calipers.
3. Hardness test: Hardness of the tablet was determined by using the Monsanto hardness
tester (n=3) the lower plunger was placed in contact with the tablet and a zero reading was
taken. The plunger was then forced against a spring by turning a threaded bolt until the tablet
fractured. As the spring was compressed a pointer rides along a gauge in the barrel to indicate
the force.
4. Friability test: This test is performed to evaluate the ability of tablets to withstand
abrasion in packing, handling and transporting.
Initial weight of 20 tablets is taken and these are placed in the Friabilator, rotating at 25rpm
for 4min.
The difference in the weight is noted and expressed as percentage.
It should be preferably between 0.5 to 1.0%.
%Friability = [(W1-W2)/W1] X 100
Where, W1= weight of tablets before test,
W2 = weight of tablets after test
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5. Assay Procedure
Accurately weigh and dissolve equivalent to 25 mg of drug in methanol and than make up to
the volume of 25ml with water it gives 1000µg/ml concentrated solution.
From above that solution 1ml was diluted to 10ml with water it will give 100µg/ml
concentrated solution.
From above that solution 1ml was diluted to 10ml with water it will give 10µg/ml
concentrated solution.
And take absorbance from UV visible spectroscopy apply in below formula
Assay = test absorbance/standard absorbance*standard concentration/sample
concentration*purity of drug/100*100
6. In vitro Dissolution Study for Immediate release granules
900 ml of 0.1N HCl (or) 6.8 phosphate buffer was placed in the vessel and the USP-II
apparatus (Paddle method) was assembled. The medium was allowed to equilibrate to
temperature of 370C±0.5
0C. A tablet was placed in the vessel and was covered; the apparatus
was operated up to 60minutes at 75 rpm. At definite time intervals, 5 ml of dissolution
medium was withdrawn; filtered and again replaced with 5 ml of fresh medium to maintain
sink conditions. Suitable dilutions were done with dissolution medium and were analyzed
spectrophotometrically at max =262 nm using a UV-spectrophotometer (Lab India).
Table 5: Dissolution parameters for Immediate release granules.
Parameter Details
Dissolution apparatus USP -Type II (paddle)
Medium 0.1N HCl (or) 6.8 phosphate buffer
Volume 900 ml
Speed 75 rpm
Temperature 37± 0.5 ºC
Sample volume withdrawn 5ml
Time points 5, 10, 15, 30, 45 and 60 min
Analytical method Ultraviolet Visible Spectroscopy
λ max 262 nm
7. In vitro Dissolution Study for pulsincap DDS
900 ml of 0.1N HCl was placed in the vessel and the USP-II apparatus (Paddle method) was
assembled. The medium was allowed to equilibrate to temperature of 370C±0.5
0C. A tablet
was placed in the vessel and was covered; the apparatus was operated up to 120 minutes at 75
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rpm. At definite time intervals, 5 ml of dissolution medium was withdrawn; filtered and again
replaced with 5 ml of fresh medium to maintain sink conditions. Suitable dilutions were done
with dissolution medium and were analyzed spectrophotometrically at max =262 nm using a
UV-spectrophotometer (Lab India). Then remove the 0.1N Hcl and replace with 6.8
phosphate buffer and continue the dissolution with the above procedure from 120 minutes.
Table 6: Dissolution parameters for Pulsincap DDS.
Parameter Details
Dissolution apparatus USP -Type II (paddle)
Medium
0.1N HCl upto 120min
And
6.8 phosphate buffer from 120min-540min
Volume 900 ml
Speed 75 rpm
Temperature 37± 0.5 ºC
Sample volume withdrawn 5ml
Time points 5, 10, 15, 30, 45, 60, 120, 180, 240, 300, 360. 420,
480 and 540 min
Analytical method Ultraviolet Visible Spectroscopy
λ max 262 nm
In vitro Release Kinetics Studies: The analysis of drug release mechanism from a
pharmaceutical dosage form is important but complicated process and is practically evident in
the case of matrix systems. The order of drug release from Pulsincap drug delivery was
described by using zero order kinetics or first order kinetics. The mechanism of drug release
from Pulsincap drug delivery was studied by using Higuchi equation and the Peppa’s-
Korsemeyer equation.
1. Zero Order Release Kinetics
It defines a linear relationship between the fractions of drug released versus time.
Q=k0t.
Where, Q is the fraction of drug released at time t and ko is the zero order release rate
constant. A plot of the fraction of drug released against time will be linear if the release obeys
zero order release kinetics.
2. First Order Release Kinetics: Wagner assuming that the exposed surface area of a tablet
decreased exponentially with time during dissolution process suggested that the drug release
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from most of the slow release tablets could be described adequately by the first-order
kinetics. The equation that describes first order kinetics is
Log C= Log Co-kt/2.262
Where C is the amount of drug dissolved at time t,
Co is the amount of drug dissolved at t=0 and
k is the first order rate constant.
A graph of log cumulative of log % drug remaining Vs time yields a straight line. Will be
linear if the release obeys the first order release kinetics.
3. Higuchi equation: It defines a linear dependence of the active fraction released per unit of
surface (Q) and the square root of time.
Q=K2t1/2
Where K2 is release rate constant. A plot of the fraction of drug released against square root
of time will be linear if the release obeys Higuchi equation. This equation describes drug
release as a diffusion process based on the Fick’s law, square root time dependent.
4. Peppa‟s-Korsemeyer equation (Power Law): In order to define a model, which would
represent a better fit for the formulation, dissolution data was further analysed by Peppa’s-
Korsemeyer equation (Power Law).
Mt/ M∞ =K.tn
Where, Mt is the amount of drug released at time t
Mα is the amount released at time α,
Mt/Mα is the fraction of drug released at time t,
K is the kinetic constant and n is the diffusion exponent.
To characterize the mechanism for both solvent penetration and drug release n can be used as
abstracted. A plot between log drug release up to 60% against log of time will be linear if the
release obeys Peppa’s-Korsemeyer equation and the slope of this plot represents ―n‖ value.
The kinetic data of the formulations were included.
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Nature of release of the drug from the designed tablets was inferred based on the correlation
coefficients obtained from the plots of the kinetic models. The data were processed for
regression analysis using MS EXCEL.
Table 7: Drug release kinetics mechanism.
Diffusion exponent(n) Mechanism
0.45 Fickian diffusion
0.45 < n <0.89 Anomalous(Non- Fickian) diffusion
0.89 Case II transport
n > 0.89 Super Case II transport
RESULTS AND DISCUSSION
1. Construction of Standard calibration curve of Nicorandil in 0.1N HCl
The absorbance of the solution was measured at 262nm, using UV spectrometer with 0.1N
HCl as blank. The values are shown in table. A graph of absorbance Vs Concentration was
plotted which indicated in compliance to Beer’s law in the concentration range 2 to 10 µg/ml.
Table 8: Standard calibration curve values.
Concentration (µg/ml) Absorbance
0 0
2 0.129
4 0.263
6 0.395
8 0.512
10 0.642
Figure 1: Nicorandil Standard calibration curve in 0.1 N Hcl.
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2. Construction of Standard calibration curve of Nicorandil in 6.8 phosphate buffer
The absorbance of the solution was measured at 262nm, using UV spectrometer with 6.8
phosphatebuffer as blank. The values are shown in table no 20. A graph of absorbance Vs
Concentration was plotted which indicated in compliance to Beer’s law in the concentration
range 2 to 10 µg/ml.
Table 9: Standard calibration curve values.
Concentration (µg/ml) Absorbance
0 0
2 0.138
4 0.281
6 0.413
8 0.556
10 0.698
Figure 2: Nicorandil Standard calibration curve in 6.8 phosphate buffer.
Evaluation studies
Table 10: Pre compression studies of Nicorandil Hydrogel plug.
Formulation
Code
Bulk density
(Kg/cm3)
Tapped
density
(Kg/cm3)
Cars index Hausners
ratio
ng e of
repose
Plug 1 0.44 0.50 12 1.1 27.92
Plug 2 0.40 0.48 16 1.2 32.73
Plug 3 0.50 0.58 13 1.16 28.58
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Inference
The blends prepared for direct compression of tablets were evaluated for their flow
properties; the results for the blends of compression tablets were shown in Table:
The bulk density and the tapped density for all formulations were found to be almost
similar.
The Carr’s index and Hausner’s ratio were found to be in the range of ≤ 18 and 1.1 to
1.23 respectively, indicating good flow and compressibility of the blends.
The angle of repose for all the formulations was found to be in the range of 27.92-34.96˚
which indicating passable flow (i.e. incorporation of glidant will enhance its flow).
Table 11: Post compression studies of Nicorandil Hydrogel plug.
Formulatio
n Code
% weight
variation
Thickness
(mm)
Hardness
(Kg/cm2)
% Friability
Plug 1 2.37 3.41 7.51 0.31
Plug 2 3.16 3.61 7.49 0.42
Plug 3 0.47 3.28 7.47 0.35
Inference
The variation in weight was within the range of ±10% complying with pharmacopoeia
specifications of USP.
The thickness of tablets was found to be between 3.28-3.61 mm.
The hardness for different formulations was found to be between 7.47 to 7.51 kg/cm2,
indicating satisfactory mechanical strength
The % Friability was within limit
Table 12: Evaluation studies of Nicorandil immediate release granules.
Formulation
Code Bulk density Tapped density Cars index
Hausners
ratio
Angle of repose
(degrees)
F1 0.325 0.375 13.33 1.15 4.7
F2 0.281 0.317 11.35 1.12 5.5
F3 0.333 0.357 6.722 1.07 6.1
F4 0.270 0.307 12.05 1.13 6.8
F5 0.25 0.289 13.49 1.15 6.7
F6 0.285 0.312 8.65 1.09 6.8
F7 0.285 0.322 11.49 1.12 6.1
F8 0.313 0.338 7.39 1.07 5.6
F9 0.312 0.338 7.69 1.08 4.5
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Inference
The prepared tablets were evaluated for their flow properties; the results for the blends of
compression tablets were shown in Table.
The bulk density and the tapped density for all formulations were found to be almost
similar.
The Carr’s index and Hausner’s ratio were found to be in the range of ≤ 18 and 1.0
respectively, indicating good flow and compressibility of the blends.
The angle of repose for all the formulations was found to be 4.5-6.8 which indicating
passable flow (i.e. incorporation of glidant will enhance its flow).
Table 13: Dissolution data of Nicorandil immediate release granules.
Time (Min) F1 F2 F3 F4 F5 F6 F7 F8 F9
0 0 0 0 0 0 0 0 0 0
5 15.47 19.52 23.45 21.21 32.46 46.98 51.34 57.28 45.33
10 19.58 23.49 31.43 28.36 43.28 54.73 69.26 73.26 77.86
15 23.42 27.44 39.32 39.13 55.23 68.76 85.31 91.32 99.54
30 51.26 57.32 78.26 51.29 69.56 81.23 98.26 99.26 97.37
45 59.38 63.25 85.33 63.16 75.37 89.38 99.98 98.05 94.23
60 72.14 78.21 97.28 79.34 93.24 99.27 99.10 95.32 89.37
Figure 3: Comparative dissolution profile for F1, F2 and F3 formulations.
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Figure 4: Comparative dissolution profile for F4, F5 and F6 formulations.
Figure 5: Comparative dissolution profile for F7, F8 and F9 formulations.
Figure 6: First order plot for F1, F2 and F3 formulations.
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Figure 7: First order plot for F4, F5 and F6 formulations.
Figure 8: First order plot for F7, F8 and F9 formulations.
Table 14: R2 and „n‟ resu t tab e.
Formulation
Code
R2 Value
Zero order First order
F1 0.984 0.998
F2 0.971 0.992
F3 0.963 0.979
F4 0.967 0.990
F5 0.916 0.967
F6 0.861 0.949
F7 0.773 0.885
F8 0.704 0.736
F9 0.642 0.356
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Inference
Among the different polymers Crospovidone was showing better drug release
F9 was showing the satisfactory results
When we plot the release rate kinetics for best formulation F9 was following zero order
because correlation coefficient value of zero order is more than first order value.
Table 15: Dissolution data of Nicorandil Pulsincap DDS.
Time (Min) Plug 1 Plug 2 Plug 3
0 0 0 0
5 37.51 39.44 41.19
10 69.85 71.49 73.36
15 99.19 98.42 99.10
30 97.43 95.35 98.39
45 90.49 92.46 93.94
60 84.42 89.41 89.72
120 0.32 0.25 0.14
180 0.05 4.36 0.26
240 17.43 8.62 0.47
300 45.35 21.53 0.49
360 98.97 79.41 1.52
420 2.52 99.45 3.29
480 0.45 5.63 5.48
540 0.33 0.26 99.49
Figure 9: Comparative dissolution profile for Plug 1, Plug 2 and Plug 3 formulations.
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Figure 10: First order for Plug 1, Plug 2 and Plug 3 formulations.
Figure 11: Higuchi plots for Plug 1, Plug 2 and Plug 3 formulations.
Figure 12: Peppas plots for Plug 1, Plug 2 and Plug 3 formulations.
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Table 16: R2 and „n‟ resu t tab e.
Formulation
Code
R2 Value
“N” Va ue Zero order First order Higuchi Peppas
Plug 1 0.456 0.305 0.397 0.531 0.959
Plug 2 0.308 0.137 0.275 0.443 0.617
Plug 3 0.334 0.126 0.365 0.558 0.929
Inference
Plug 3 was showing the satisfactory results
When we plot the release rate kinetics for best formulation Plug 3 was following zero
order because correlation coefficient value of zero order is more than first order value.
FT-IR spectroscopy for Nicorandil
The FTIR spectra‟s, observed that the characteristic absorption peaks of pure Nicorandil
were obtained. The spectral data suggests that the major peaks for drugs are obtained as
nearer value and there were no considerable changes in IR peaks in all physical mixtures of
drug and polymers. This indicates that the drugs were molecularly dispersed in the polymers
or in drug loaded formulations thus thereby indicating the absence of any interactions.
Figure 13: IR graph for Nicorandil.
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Figure 14: IR graph for Crospovidone.
Figure 15: IR graph for HPMC K200M.
Figure 16: IR graph for Nicorandil + Crospovidone.
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SUMMARY AND CONCLUSION
1. Suitable analytical method based on UV-Visible spectrophotometer was developed for
Nicorandil. λmax of 262 nm was identified in phosphate buffer solution, pH 6.8.
2. HPMC K200M polymer was used in different ratios for hydrogel plug preparation. And
HPMC K200M was respectively showed better pulsatile drug release of Nicorandil.
3. When polymer concentration increases the release rate decreases this is because of reason
when the concentration of polymer increases the diffusion path length increases
4. Hydrogel plug granules was showed satisfactory results for all pre and post compression
studies.
5. Nicorandil immediate release granules were prepared by wet granulation method using
Sodium starch glycolate, Croscarmellose sodium and Crospovidone.
6. Crospovidone was given better release when compared with other polymers.
7. Formulation F9 was selected for puls in cap drug release.
8. Formulation F9 was tried with all 3 plugs for puls in cap drug delivery system.
9. Plug-3 gave better-pulsatile drug release when compared with other 2 plugs.
10. The most probable mechanism for the drug release pattern from the formulation was
Super Case II transport.
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