Effect of Different Viscosity Grade of HPMC on Cefixime Trihydrate Sustained Release Matrix Tablet
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Transcript of Effect of Different Viscosity Grade of HPMC on Cefixime Trihydrate Sustained Release Matrix Tablet
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ISSN No: 2321 8630, V 1, I 1, 2014 Journal Club for Pharmaceutical Sciences (JCPS)
Manuscript No: JCPS/RES/2014/18, Received on: 04/08/2014, Revised on: 10/08/2014, Accepted on: 14/08/2014
RESEARCH ARTICLE
All Rights Reserved by Journals Club & Co. 115
Effect of Different Viscosity Grade of HPMC on Cefixime Trihydrate Sustained Release Matrix Tablet
Patel BP*1, Patel BK1 1Kalol Institute of Pharmacy, Gandhinagar, Gujarat, India.
ABSTRACT
The present work aims to study effect of different viscosity grade of HPMC on cefixime trihydrate sustained release matrix tablet with a view to prolong drug release in vivo and reduce frequency of dosing. Cefixime Trihydrate is an orally active third generation cephalosporin. It has plasma half-life of 3-4 hrs. It is active against Gram+ve as well as Gram-ve bacteria. The Sustained release matrix tablets were prepared by wet granulation method using various release retardant polymers like different grade of HPMC, Lactose, MCC, and PVP K-30. The granules were subjected to pre-compression and post-compression parameters and they were in the acceptable limits. The in vitro retardation of drug release from HPMC matrices in accordance with its different proportion and viscosity grade was HPMC K-100M>HPMC K-15M >HPMC K-4M with ratio of (1, 1.5, 2) individually in formulation F1-F9 and (0.5, 0.75, 1) ratio in F10-F12. Among various kinetic models drug release was found to best fit the case II transport, Zero order release model. A drug-excipient interaction was performed by DSC and FTIR; results were shown that there was no interaction between drug and excipients used. After 3 months stability study at 400C/75% RH, formulations found to be stable. So as the viscosity and proportion of HPMC increases release rate from sustained release cefixime trihydrate matrix tablet decreases.
KEYWORDS
Sustained release matrix tablet, Cefixime Trihydrate, HPMC, Antibiotic
INTRODUCTION
The oral route is the most acceptable drug
delivery route for patient compliance aspects.
The main goal of pharmaceutical formulation
is to achieve better therapeutic activity by
using smallest quantity of drug administered
by the most suitable route.1In some sustained
release formulations, the drug dissolves into
the matrix, and the matrix physically swells to
form a gel, allowing the drug to exit through
the gel's outer surface. Sustained release
tablets and capsules are commonly taken only
once or twice daily, compared with
*Address for Correspondence: Parth.B. Patel, Kalol Institute of Pharmacy,
Gandhinagar, Gujarat, India. Email id: [email protected]
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All Rights Reserved by Journals Club & Co. 116
counterpart conventional forms that may have
to take three or four times daily to achieve the
same therapeutic effect.2
One of the most common approaches used
for prolonging and controlling the rate of
drug release is incorporating the drug in a
hydrophilic colloidal matrix such as Hydroxy
propyl methyl cellulose (HPMC), Hydroxy
propyl cellulose (HPC), carbopols, chitosan,
alginates and gelatin etc. The mechanism and
kinetics of release of drugs incorporated in
these polymer matrices is depends the type
and amount of polymer as well as on the
physico-chemical properties of drug
substance. Hydrophilic polymer matrix
systems are widely used in oral controlled
drug delivery because they make it easier to
achieve a desirable drug-release profile, cost
effectiveness and they have broad US Food
and Drug Administration acceptance. The
hydration rate of HPMC depends on the
nature of these substituents, such as the
molecular structure and the degree of
substitution. Specifically, the hydration rate
of HPMC increases with an increase in the
hydroxyl propyl content. The solubility of
HPMC is pH independent. 3
Cefixime Trihydrate is broad spectrum third
generation cephalosporin antibiotic having
bactericidal activity and used in the treatment
of uncomplicated UTI, otitis media,
pharyngitis, and acute exacerbation of chronic
bronchitis, uncomplicated gonorrhea. It has
very good in vitro activity against
Streptococcus pneumonia, Streptococcus
pyogenes, Branhamella catarrhalis,
Haemophilus influenza, Escherichia coli,
Klebsiella pneumoniae, Proteus mirabilis and
Neisseria gonorrhoeae. It also has activity
against Gram-+ve bacteria, especially against
Streptococci.4
After 200 mg of the conventional release
dosage form of Cefixime trihydrate is
administered, the peak plasma concentration
achieved is 1.2 mg/L, and this concentration
slowly decline below minimum effective
concentration (MEC) within 12 hours.
Cefixime trihydrate inhibit mucopeptide
synthesis in the bacterial cell wall, rendering
it defective and osmotically unstable. The
steady-state maintenance of plasma
concentration will increase the rate of
bacterial killing and more quickly relieve the
excruciating symptoms of bacteremia.
The present research work involves the
formulation development of sustained release
matrix tablet of cefixime trihydrate by
applying full factorial design to understand
the effect of formulation variables like
concentration and viscosity of HPMC K-4M,
HPMC K-15M, HPMC K-100M on physico-
chemical properties of matrix tablet and on in
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All Rights Reserved by Journals Club & Co. 117
vitro dissolution rate and stability were also
studied. The drug release data were plotted
using various kinetic models to evaluate the
drug release mechanism and kinetics.6
MATERIALS & METHODS
Cefixime Trihydrate was gifted to us by
Alembic pharmaceuticals; Baroda,
Gujarat.HPMC K-4M, HPMC K-15M,
HPMC K-100M, microcrystalline cellulose
(MCC), Lactose and Polyvinyl pyrrolidone
(PVP K-30) was procured from Merck India
Ltd., Mumbai. Polymers used were of
analytical grade and other chemicals of
Laboratory grade.
Preparation of Cefixime Trihydrate
Sustained Release Matrix Tablet1, 7
Different viscosity grade of HPMC based
sustained release matrix tablets were prepared
by wet granulation technique. The
compositions of different tablet formulations
are shown in the table-1. PVP-K30 is used as
a binder in 25%, Micro Crystalline Cellulose
(7-15%), Lactose (13-23) was widely used as
a binder/diluent that makes it useful in
tableting. The formulations F-1 to F-3 are
composed of HPMC K-4M, whereas
formulations F-4 to F-6 are composed of
HPMC K-15M and Formulations F-7 to F-9
were composed of HPMC K-100M in various
percentages too (like-100,150,200). First
Polymers & other materials were weighed and
then passed through sieve 20, loading in
RMG premixing for 10min.Then binder PVP
K-30was added for 5min after that kneading
for 3min then run the chopper (500rpm) for
2min dried in hot air oven then again passed
through sieve no 20 at finally add lubricant
and glidant (mg. stereate, talc) and compress
in rotary press compression machine by using
11-mm punches at a compression force
required to produce tablets of about 812
kg/cm2 hardness. All the tablets were stored
in airtight containers for further study. Prior
to compression, granules were evaluated for
their flow and compressibility characteristics.
Evaluation of Cefixime Trihydrate Sustained
Release Matrix Tablet10-15
Pre-compression Parameters8, 9 BulkDensity:
Weight of the Powder Volume of the packing
Tapped
Density:Weight of the powder Tapped volume of the packing Hausners
Ratio: Bulk Density Tapped Density Carrs Compressibility Index Tapped Density Bulk DensityTapped Density 100 Angle of Repose Tan = h/r OR = tan-1 [h/r]
Post-Compression Parameters10-15
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All Rights Reserved by Journals Club & Co. 118
The prepared tablets can be evaluated for
various official and non official
specifications.
Thickness and Diameter of Tablets
Three tablets were taken and the thickness
and diameter was measured using a dial-
caliper. The tablet thickness and diameter
should be controlled within the 5%
variation of a standard value.
Weight variation test as per I.P 9610 6 Tablets were randomly selected from each
batch and weighed on an electronic balance
both weight of 6 tablets and individual tablet
was considered mean and standard deviation
(S.D) of weight was calculated from each
batch and shown in table -3.
Hardness10 Hardness indicates the ability of a tablet to
withstand mechanical shocks while handling.
The hardness of the tablets was determined
using Monsanto hardness tester. It is
expressed in kg/cm2. Three tablets were
randomly selected from each formulation and
the mean and standard deviation values were
calculated.
Friability (%)10 It is the ability of tablets to withstand
mechanical shocks during handling and
transportations. The % of friability of
prepared tablet was shown in table-3. 6 tablets
were randomly picked from each batch and
weighed and placed in the Rouche friability
test apparatus and operated at rate of 25 RPM
for 4 minutes (or up to 100 revolutions),
tablets were de-dusted and weighed again.
The loss of tablet weight due to abrasion and
fracture was measured in terms of % friability
(A value of
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All Rights Reserved by Journals Club & Co. 119
ml of pH 7.2 Phosphate buffer and dissolved
completely and made upto 100 ml with
buffer. This solution was filtered by whatman
filter paper. From this 10 ml of solution was
withdrawn and volume made upto 100 ml
using buffer. The absorbance was measured at
288 nm using an UV spectrophotometer. The
experiments were carried out in triplicate for
the tablets of all formulations and average
values were recorded as shown in table 3
Composition of Phosphate Buffer pH 7.2
Ingredients Quantity Potassium dihydrogen phosphate (KH2PO4) 26.22g
Sodium Carbonate (Na2CO3) 7.78 g
Magnesium Chloride 5 ml
Distilled Water Up to 1000ml
In-vitroDrug Release Study14 The dissolution test was performed according
to USP type-II paddle apparatus (Electolab,
Mumbai). The dissolution medium consists of
900 ml of Phosphate buffer of pH 1.2 for two
hours, followed by Phosphate buffer pH 7.2
for the next ten hours at 370.5C with a
rotation rate of 100 rpm. 10 ml aliquots of
samples were taken at every 1 hr and replaced
with the same. Cefixime Trihydrate was
assayed spectrophoto- metrically at 288 nm
(UV-Thermo scientific). The release studies
for each formulation were conducted in
Phosphate buffer pH 1.2 and pH 7.2,
indicating the reproducibility of the results.
The results were expressed as each value is
the mean SD, n = 3 determinations.
Kinetic analysis of in vitro release data
In order to determine the release mechanism
that provides the best description pattern of
drug release, the in vitro release data were
fitted to zero-order, first-order Higuchi matrix
model and KorsmeyerPeppas model. The
release exponent (n) was calculated by
regression analysis using the following
equation. Mt/ M = Kt, Where Mt/M is the
fraction of drug released (using values of
Mt/M within the range 0.100.60) at time t
and K is a constant incorporating the
structural and geometric characteristics of the
release device. A value of n=0.5 indicates
case I (Fickian) diffusion, 0.5
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sustained release matrix tablet, the values of
R2 (coefficient of determination) has been
obtained as presented in table -5.[15]
Stability studies:[2, 6] The formulations (F3, F6, F9, F10, F11, F12)
were also subjected to stability studies by kept
them for 3 months under environmental
conditions such as room temperature of 27
2C/65% RH, oven temperature of 40
2C/75% RH and in the refrigerator at 48C.
At the end of the period, Hardness, drug
content, and release profiles were determined.
Drug Excipient Interaction Studies
The Cefixime Trihydrate drug &F10tablet
were subjected to thermal analysis by
Differential Scanning Calorimetry (DSC) to
confirm the absence of any interactions.
Instrument Model no- DSC-60, Temp range-
500C-3000C, Rate-200Cper min., Atmosphere
Air and Made by- shimadzu corporation,
Japan.[12-15]
Fourier Transforms Infrared Spectroscopy
Studies (FTIR)
Fourier transform infrared spectrum of
Cefixime Trihydrate pure drug, physical
mixture of pure drug and polymers were taken
respectively. Potassium bromide disc (pellets)
method. All the spectra were scanned from
4000 cm-1 to 500 cm-1.10, 15
RESULT AND DISCUSSION
Cefixime Trihydrate Sustained Release
Matrix Tablet was designed with the objective
of prolong drug release leading to minimize
the peak and valley effect in the plasma and
provide patient convenience. Therefore,
Hydrophilic polymer matrix systems are
widely used in sustained release matrix tablet
because they make it easier to achieve a
desirable drug-release.
Pre-Compression Parameters
Angle of Repose
Formulation F3-F12 having angle of repose
between 23-30 which shows excellent flow
property. Formulation F1-F2 having angle of
repose between 31-35 which showed good
flow property.
Carrs Compressibility Index
All the formulation F1-F12 shows Carrs
Compressibility index between ranges 5-
15which indicate excellent flow property.
Post-Compression Parameters
It was observed that Thickness, Diameter,
Weight Variation, Swelling Indexwere found
to be satisfactory.
Hardness
All the formulation F1-F12 shows hardness
between 8-11 kg/cm2 which was effective for
sustained drug release. It was found that as
the concentration and grade of HPMC
increases hardness increases.
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All Rights Reserved by Journals Club & Co. 121
Friability
The percent friability for all the formulations
was below 1%, indicating that the friability is
within the prescribed limits. The results of
friability indicate that the tablets possessed
good mechanical strength.
Drug Content
The percentage drug content of both the drugs
in all the formulated tablets was found to be
within limit. Percentage drug content values
of Cefixime Trihydrate are within 93.17 to
98.67 % for all the formulations. The results
within range indicate uniformity of mixing.
In vitro Dissolution Studies In vitro drug release study was carried out
using USP dissolution apparatus, type-II.
Comparative dissolution profile of all batches
is given in Figure 1. Being the sustained
release formulations the release rates of all the
formulations were controlled. Formulation
F10 released Cefixime Trihydrate completely
slower. This may be due to HPMC K-100M,
K-15M and K-4M in ratio of (1-0.75-0.5) that
result in decrease wettability and penetration
of water into the film matrices and hence
decrease diffusion of the drug. Whereas
release rates of other formulation were
comparatively higher than F10.
Drug release from HPMC matrices
showed that viscosity and proportion of
polymer plays important role in
retardation of drug release was in
following order specifically for F1-F9
HPMC K-100M > HPMC K-15M > HPMC
K-4M
The retardation of drug release from
HPMC matrices in accordance with its
different proportion was in the following
order specifically for F10-F12.
HPMC K-4M HPMC K-15M HPMC K-100M INFERENCE
0.5 0.75 1 SLOWEST
0.75 1 0.5 SLOWER
1 0. 5 0.75 SLOW
Kinetic Analysis of in vitro Release Data
In order to determine the release mechanism
that provides the best description pattern of
drug release, the in vitro release data were
fitted to zero-order, first-order, and Higuchi
matrix model and KorsmeyerPeppas model.
The release data were matched kinetically
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All Rights Reserved by Journals Club & Co. 122
with case II transports (Zero order release
model).
Drug Excipient Interaction Studies
As per DSC study of drug shows the
characteristic peak at 220.60C as its melting
point is 220-222 C reported. The figure 3
showed the characteristic peak of Cefixime
Trihydrate alone. The figure showed the
combined peaks of Cefixime Trihydrate
HPMC grades, PVP K30.DSC study of drug
and F10 matrix tablet showed sharp peak at
221.16C, 109.24C, 97.70C, 89.66C
respectively. Theses confirmed drug
compatibility with polymer. All the peaks
were present in graph and hence the Cefixime
Trihydrate was not being interfered due to
presence of other Excipients.
Infrared Spectroscopy Studies (I.R.)
The figure 2b shown characteristics peaks of
Cefixime Trihydrate are obtained at 3567.18
cm-1, 3296.24 cm-1, 1774.13 cm-1, 1667.30
cm-1, 1583.11 cm-1, 1531.88 cm-1, 1225.19
cm-1, 1185.98 cm-1, 803.17 cm-1, 864.64 cm-1
and 741.90 cm-1. FTIR spectrum of Cefixime
Trihydrate pure drug, physical mixtures of
drug and the polymers were taken. The FTIR
spectra obtained indicates good compatibility
between drug and polymers.
Stability Studies
There was no significant change observed in
the physical appearance, hardness and drug
content uniformity tests as conducted at the
end of 3 months. The in-vitro dissolution
profile for formulation F10 stored at 25 0C/40% RH exhibited 74.78% release of
Cefixime Trihydrate, while for formulation
stored at 400C/75%RH, Cefixime Trihydrate
accounted for 74.00% release. Therefore the
stability studies revealed no change in
physical appearance, Hardness, Drug content
and not much change in In-vitro dissolution
profiles. Hence these formulations were found
to be stable at the above temperatures.
DISCUSSION
This investigation showed effect of HPMC on
release rate of drug with the intention of
obtaining better therapeutic efficiency by
controlling drug release thereby improving
patient compliance and increasing
bioavailability with decreased dosing and
fewer side effects. Prepared tablets did not
disintegrate, however a gel layer was formed
on surface of the tablet due to swelling of
HPMC in presence of water. Here the
polymer ratios of each type of HPMC K- 4M,
K-15M and K-100M were kept individually
in (1, 1.5, 2) for F1-F9. For F10-F12 these
ratio was kept (0.5, 0.75, 1) respectively. The
formulations containing HPMCK-100M
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All Rights Reserved by Journals Club & Co. 123
showed delayed release of drug as compared
to those containing HPMC K-15M and
HPMC K- 4M. These revealed that as the
viscosity of HPMC increased, the rate of drug
release was decreased. Formulation of
sustained release matrix tablets of Cefixime
Trihydrate thus helped to decrease dosing
frequency , reduces local adverse effects, and
extends release of drug from the matrix to a
prolong period of time, thus improves patient
compliance. This may also extends biological
half-life of existing drug.
Table : 1 Formulation of Cefixime Trihydrate Sustained Release Matrix Tablet (Wt. in mg)
FORMULATION CODE
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12
CEFIXIME TRIHYDRATE
200 200 200 200 200 200 200 200 200 200 200 200
HPMC K 4 M (4,000 mPa s)
100 150 200 - - - - - - 50 75 100
HPMC K 15 M (15,000 mPa s)
- - - 100 150 200 - - - 75 100 50
HPMC K 100 M
(100,000 mPa s) - - - - - - 100 150 200 100 50 75
LACTOSE 125 100 75 125 100 75 125 100 75 45 45 45
MCC 90 65 40 90 65 40 90 65 40 45 45 45
PVP K 30 25 25 25 25 25 25 25 25 25 25 25 25
Mg. STEARATE 4 4 4 4 4 4 4 4 4 4 4 4
TALC 6 6 6 6 6 6 6 6 6 6 6 6
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Table : 2 Pre-Compression parameters of Sustained Release Matrix Tablet
Code (F)
Bulk Density (g/cc)
Tapped Density (g/cc) Hausner Ratio
Carrs Compressibility
index (%)
Angle of Repose (o)
F1 0.405 0.0035 0.454 0.0000 1.121 0.0098 10.79 0.7627 32.55 0.4792 F2 0.417 0.0000 0.459 0.0046 1.102 0.0110 9.21 0.9180 31.48 0.4503 F3 0.426 0.0040 0.475 0.0046 1.113 0.0185 10.17 1.4905 29.98 0.4215 F4 0.438 0.0000 0.487 0.0058 1.111 0.0133 9.99 1.0750 30.23 0.4215 F5 0.459 0.0046 0.517 0.0064 1.126 0.0029 11.21 0.1986 29.28 0.3984 F6 0.478 0.0052 0.536 0.0064 1.121 0.0254 10.75 2.0150 27.97 0.3637 F7 0.503 0.0058 0.564 0.0075 1.120 0.0277 10.68 2.2309 28.61 0.3811 F8 0.521 0.0000 0.590 0.0081 1.133 0.0156 11.73 1.2182 27.15 0.0000 F9 0.536 0.0064 0.604 0.0081 1.128 0.0146 11.36 1.1221 26.38 0.3291
F10 0.610 0.0150 0.707 0.0115 1.160 0.0159 13.81 1.1872 23.34 0.2540 F11 0.590 0.0162 0.676 0.0000 1.146 0.0312 12.67 2.3914 24.61 0.2887 F12 0.564 0.0075 0.652 0.0095 1.158 0.0285 13.57 2.1344 25.47 0.5300
Each value is the mean, n = 3 determinations
Table : 3 Post-Compression parameters of Sustained Release Matrix Tablet
Code (F)
Thickness (mm)
Diameter (mm)
Weight Variation
(mg) Hardness (kg/cm2)
Friability (%)
Swelling Index (%)
% Drug Content
F1 3.50 0.0000 11.02 0.0000 550.67 1.1547
8.57 0.0577 0.41 61.81 93.17
F2 3.53 0.0115 11.08 0.0058 550.00 1.0000
8.73 0.0577 0.36 63.81 93.83
F3 3.55 0.0115 11.13 0.0173 550.67 1.1547
8.83 0.0577 0.29 66 94.67
F4 3.57 0.0115 11.17 0.0058 551.33 1.5275
8.97 0.0577 0.30 62.91 95
F5 3.60 0.0000 11.21 0.0115 549.33 1.1547
9.03 0.0577 0.27 65.64 96.17
F6 3.64 0.0000 11.30 0.0000 549.33 0.5774
9.20 0.0000 0.25 66.90 96.5
F7 3.63 0.0115 11.35 0.0058 549.33 2.0817
9.33 0.0577 0.22 66.36 96.83
F8 3.65 0.0115 11.37 0.0115 551.67 1.5275
9.47 0.0577 0.21 68.91 97
F9 3.68 0.0000 11.43 0.0306 550.33 0.5774
9.70 0.1000 0.23 70.18 97.67
F10 3.71 0.0115 11.63 0.0115 548.67 1.1547
10.43 0.0577 0.11 75.45 98.67
F11 3.70 0.0000 11.56 0.0153 550.67 1.1547
10.23 0.0577 0.16 73.27 97.67
F12 3.69 0.0115 11.51 0.0058 550.00 1.0000
9.97 0.0577 0.18 72.18 97.17
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Each value is the mean SD, n = 3 determinations
Table : 4 In-vitro drug release data of Cefixime Trihydrate Sustained Release Matrix Tablet
Time (Hrs.)
Percentage cumulative drug released F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12
1 20.01 17.18 13.06 16.41 12.03 11.26 10.75 9.21 7.92 5.61 8.43 13.83 2 26.14 26.88 21.95 25.07 22.97 16.79 17.30 17.54 12.89 13.64 15.73 19.39 3 30.84 33.16 27.71 33.91 30.29 25.08 26.11 23.54 21.69 20.16 21.47 26.39 4 37.32 39.14 34.97 38.89 36.54 35.97 32.89 30.29 28.99 27.69 30.01 31.87 5 44.59 45.12 40.96 46.15 43.81 40.20 42.48 38.85 34.98 33.68 36.28 40.41 6 56.24 53.93 50.29 54.97 52.37 48.73 49.79 46.92 46.11 41.21 42.52 46.94 7 62.54 60.20 53.99 59.18 58.13 54.49 57.33 53.44 51.11 44.63 49.79 48.81 8 74.95 69.01 59.94 62.06 66.16 59.95 65.12 60.71 58.63 52.90 56.30 51.66 9 83.32 72.71 67.21 77.00 74.48 67.98 71.64 67.22 64.62 58.90 61.77 63.52 10 90.09 80.72 73.97 79.23 80.48 70.90 77.37 73.97 73.17 64.63 68.26 67.25 11 96.08 87.49 80.99 88.51 84.92 78.13 83.34 78.93 79.70 70.35 75.27 76.29 12 99.23 91.94 86.73 95.55 90.63 84.64 92.67 86.19 81.83 74.78 79.21 82.05
Each value is the mean, n = 3 determinations
Table : 5 Kinetic analysis parameters for Cefixime Trihydrate Sustained Release Matrix Tablet
Formulation code
Model (R2) Zero order First order Higuchi Korsemeyer-peppas
F1 0.9903 0.7973 0.9581 0.9609 F2 0.9974 0.9248 0.9811 0.9926 F3 0.9981 0.9404 0.9807 0.9967 F4 0.9932 0.8472 0.9721 0.9918 F5 0.9956 0.9455 0.9871 0.9980 F6 0.9934 0.9625 0.9877 0.9939 F7 0.9976 0.9035 0.9829 0.9972 F8 0.9981 0.9532 0.9825 0.9987 F9 0.9952 0.9659 0.9797 0.9952 F10 0.9968 0.9812 0.9869 0.9949 F11 0.9982 0.9717 0.9836 0.9992 F12 0.9916 0.9341 0.9664 0.9869
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Fig : 1 In vitro drug release and Kinetic analysis parameters for Cefixime Trihydrate Sustained Release Matrix Tablet
Fig : 2a FTIR peaks of various functional groups of Cefixime Trihydrate + Polymers
Fig: 2b FTIR peaks of various functional groups of Cefixime Trihydrate
0102030405060708090
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Perc
enta
ge cu
mul
ativ
e dru
g re
leas
ed
Time (Hrs.)
In-vitro Drug Release Study
F1
F2
F3
F4
F5
F6
F7 -0.500
0.000
0.500
1.000
1.500
2.000
2.500
0 1 2 3 4 5 6 7 8 9 10 11 12
Log
% C
D R
emai
ning
Time (Hrs.)
FIRST ORDER RELEASE
F1
F2
F3
F4
F5
F6
F7
0102030405060708090
100
0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50Perc
enta
ge c
umul
ativ
e dr
ug r
elea
se
T
HIGUCHI MODEL
F1
F2
F3
F4
F5
F6 0.0000.2500.5000.7501.0001.2501.5001.7502.000
0.000 0.500 1.000 1.500
Log
% C
DR
Log Time (Hrs.)
KORSEMEYER-PEPPAS MODEL
F1
F2
F3
F4
F5
F6
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Cefixime Trihydrate Cefixime Trihydrate + Polymers (F10) Fig : 3 DSC curves of Cefixime Trihydrate Sustained Release Matrix Tablet
Table : 6 Stability Study Data of Cefixime Trihydrate Sustained Release Matrix Tablet
code
STABILITY STUDY DATA (mean S.D , n = 3)
Hardness (kg/cm2) Drug Content In vitro Drug Release
Initial After 3 months
(400C 75%RH)
Initial After 3 months
(400C 75%RH)
Initial After 3 months
(400C 75%RH)
F3 8.83
0.0577 8.78 0.0153 94.67 92.02 86.73 85.22
F6 9.20
0.0000 9.14 0.0000 96.5 95.75 84.64 83.20
F9 9.70
0.1000 9.64 0.0153 97.67 95.00 81.86 79.82
F10 10.43
0.0577 10.36 0.0577 98.67 97.14 74.78 74.00
F11 10.23
0.0577 10.19 0.0000 97.67 96.45 79.21 78.14
F12 9.97
0.0577 9.91 0.0577 97.17 95.68 82.05 81.11
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HOW TO CITE THIS ARTICLE Patel, B, P., Patel, B, K. (2014). Effect of Different Viscosity Grade of HPMC on Cefixime Trihydrate Sustained Release Matrix Tablet. Journal Club for Pharmaceutical Sciences (JCPS), 1(I), 115-129