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Nep, E.I. and Conway, Barbara R

Polysaccharide gum matrix tablets for oral controlled delivery of Cimetidine

Original Citation

Nep, E.I. and Conway, Barbara R (2010) Polysaccharide gum matrix tablets for oral controlled
delivery of Cimetidine. Journal of Pharmaceutical Sciences and Research, 2 (11). pp. 708-716.
ISSN 0975-1459

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 E.I.Nep et al /J. Pharm. Sci. & Res. Vol.2 (11), 2010,708-716

Polysaccharide gum matrix tablets for oral controlled delivery of Cimetidine

E. I. Nep1, B. R. Conway2
1
Department of Pharmaceutics and Pharm. Technology, University of Jos, Nigeria.
2
Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH

ABSTRACT
Matrix-based tablets using 40 %w/w grewia gum were prepared by direct compression to contain
cimetidine as novel drug. The formulations were compared with similar formulations using
hydroxypropyl methylcelluose (Methocel®), gum arabic, carboxy methylcellulose (Blanose®), or
ethyl cellulose (Ethocel®) as polymer matrix. Also binary composite matrices containing grewia
gum and the reference polymers (40 %w/w total polymer concentration in a ratio of 1:1) were
directly compressed. In addition to tablet properties, swelling, erosion, kinetics of drug release from
the matrices and stability of the tablet formulations were also investigated. In vitro drug release
studies reveal that grewia gum can control the release of cimetidine from tablets for up to 12 hours.
This strong sustained-release potential of grewia polysaccharide gum was superior to hydrophilic
matrices of hydroxypropyl methylcellulose, carboxy methylcellulose and gum arabic. The release
of drug from the grewia polysaccharide gum matrices follows Higuchi kinetic models. There was
synergy between grewia gum and HPMC in delaying the release of cimetidine from tablets. Grewia
gum may therefore prove a useful excipient when used alone, or in combination with other
polymers to modify the release of soluble drugs from polymeric matrices.
Key words: Grewia gum, cimetidine, matrix tablets, controlled delivery.
dispersions of the pulverised inner stem bark
INTRODUCTION of grewia gum hydrates and swell to form a
A number of approaches have been used to highly viscous dispersion. This property of
obtain controlled drug release, but the plant has kindled a lot of interest into the
hydrophilic matrix is recognized as the potential application of the gum as matrix for
simplest and is the most widely used. Upon oral controlled delivery of medicaments. The
ingestion of a hydrophilic matrix tablet drug gum has been isolated and some
release results initially from swelling which physicochemical [12, 13], binding [14],
causes a gel layer to form on the tablet rheological [15] and mechanical properties of
surface. This gel layer retards further ingress aqueous based grewia gum films [16] have
of fluid and subsequent drug release. The been evaluated.
swelling of the polymer matrix very often The formulation of a suitable oral drug
occur simultaneously with erosion [1], and delivery system for the controlled delivery of
both of them contribute to the overall drug- highly water soluble drugs is a challenging
release rate. Hydrophillic matrices from task to the formulation scientist [17]. This is
natural polysaccharide gums such as xanthan because most highly water-soluble drugs can
gum [2, 3, 4, 5], guar gum [6, 7, 8] and karaya readily release the drug from the tablet matrix
gum [9] have been shown to provide varying faster than desired if not properly formulated.
degrees of sustained release of medicaments. In this study single polymer matrix tablets of
These natural hydrophilic colloids are still cimetidine were formulated by direct
widely used in pharmaceutical dosage forms compression technique using 40 %w/w
because of their biocompatibility, low cost grewia gum. The tablet properties and release
and free availability [10]. from the tablets were compared with
Grewia polysaccharide gum is obtained by corresponding tablets made with the
extraction from the inner stem bark of the hydrophilic polymers – hydroxypropyl
plant Grewia mollis (Family, Tiliaceae). The methylcellulose (HPMC), gum arabic, or
plant is found growing abundantly wild or carboxy methylcellulose (CMC), and
cultivated in the middle belt region of Nigeria hydrophobic polymer ethyl cellulose.
and forms part of the delicacies of the Synergism between the reference polymers
inhabitants of the region [11]. Aqueous and grewia gum was evaluated by
formulation of directly compressed binary

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matrices containing 40% total polymer density tester (Sotax TD2, Switzerland) and
concentration in the ratio 1:1. the Hausner ratio was calculated as the ratio
of tapped to bulk densities.
MATERIALS AND METHODS Characterization of tablets
Materials Crushing strength, friability, uniformity of
Ethyl cellulose (Ethocel® - standard 100FP weight and content of the tablets were
Premium) and hydroxypropyl methylcellulose evaluated. Tablet crushing strength was tested
(Methocel® K100 premium LVCR) was a gift with the model 6D tablet tester (Schulinger
from Colorcon, England. Colloidal silicon Pharmatron, Manchester, NH). Friability was
dioxide (Aerosil®) was a gift from Evonik, tested using Roche friability testing
UK. Carboxy methylcellulose (Blanose® – apparatus. The uniformity of weight test (20
Type 7M1F-PHARM) was a gift from tablets) was carried out on a class A balance.
Aqualon. Cimetidine was a free gift from Uniformity of content test (10 tablets) was
GlaxoSmithkline, UK. Gum arabic, lactose done on all batches of matrix tablets in
monohydrate, magnesium stearate were phosphate buffer (pH 7.2) and UV absorbance
purchased from Sigma, England. Grewia gum read at 228 nm on a Mattson Galaxy 3020 UV
(air-dried) was extracted from our laboratory spectrophotometer (Unicam, England).
as described previously [13]. In vitro drug release studies
Preparation and analysis of tablets Cimetidine release from the matrix tablets
Single polymer and binary composite matrix was studied in 900 mL of phosphate buffer
tablets of cimetidine were prepared by direct (pH 7.2) using the USP II (paddle method) at
compression. The single polymer matrix 100 rpm and 37 ± 1°C. The dissolution
tablets of cimetidine were made using ethyl equipment was an Erweka, DT 600 (Erweka,
cellulose, HPMC, carboxy methylcellulose, Germany) equipped with a 40 mesh sinker. A
gum arabic (reference polymers), or grewia 4 mL sample was withdrawn at time intervals
polysaccharide gum (test polymer) as the of 15 minutes, 30 minutes and thereafter
polymer matrix according to the formula every 1 hour for 12 hours for both single
shown in table 1. Binary composite matrix polymer and binary composite matrix
formulations were made using the same systems. The withdrawn samples were
polymers in a ratio of 1:1 according to the assayed in a UV-spectrophotometer at 228
formula shown in table 2. Briefly, all the nm. After each sampling, and equal volume
powders were passed through a sieve of 250 (4 mL) of fresh buffer solution with same
µm before direct compression. The amounts temperature was replaced.
of polymer, microcrystalline cellulose and Water uptake and erosion studies
cimetidine as shown in the tables were Water uptake and erosion studies were also
accurately weighed, manually blended and carried out in the dissolution apparatus DT
characterised prior to compression. The 600 (Erweka, Germany). The matrix tablets,
powders were compressed in a single station in a sinker, were placed in 900 mL of
press, Minipress MII (RIVA, Germany) after phosphate buffer (pH 7.2) equilibrated at 37 ±
blending with magnesium stearate and 1°C and the paddle rotating at 100 rpm. The
colloidal silicon dioxide to give flat faced tablets were allowed to hydrate, swell and
tablets of about 500 mg weight, 13mm erode at different time intervals. Two tablets
diameter and an average hardness of 80 N. were used per time point. At the
The compressed tablets were stored in air predetermined times (0, 30 minutes, 1, 2, 4 or
tight containers for evaluation. 8 hours), the tablets were removed from the
dissolution vessel and lightly patted with
Characterization of powders tissue paper to remove excess water. The wet
Moisture content was determined using a weight of the tablets was determined and then
Sartorius moisture balance (Satorius, they were dried at 50 °C until a constant
Germany). Angle of repose was determined weight. This remaining dry weight was
by the funnel method. Bulk and tapped recorded.
density were determined by the USP tap

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Table 1: Batch formula for directly compressed single polymer matrix tablets of Cimetidine
Ingredients Amounts
Cimetidine (mg) 250
Polymer (mg) 100
Microcrystalline cellulose (mg) 125
Magnesium stearate (mg) 4.75
Colloidal silicon dioxide (mg) 14.25

Table 2: Batch formula for directly compressed binary composite matrix tablets of cimetidine
Ingredients I II III IV V
Cimetidine (mg) 250 250 250 250 250
Grewia (mg) 50 50 50 50 50
Ethyl cellulose (mg) 50 - - - -
CMC (mg) - - 50 - -
Methocel® (mg) - - - 50 -
Gum arabic (mg) - - - - 50
Microcrystalline cellulose 125 125 125 125 125
Colloidal silicon dioxide (mg) 14.25 14.25 14.25 14.25 14.25
Magnesium stearate (mg) 4.75 4.75 4.75 4.75 4.75

Water uptake and erosion were determined incorporating structural and geometric
gravimetrically according to the following characteristics of the tablet; and n is the
equations: diffusional exponent indicative of the
% mechanism of drug release. To determine the
100 release exponent, the log value of percentage
..equation 1 drug dissolved was plotted against log time
% for each batch according to the equation. A
value of n = 0.5 indicates Fickian (case I)
100
release; >0.5 but <0.89 for non-Fickian
…equation 2 (anomalous) release; and >0.89 indicates
Kinetic analysis of dissolution data super case II type of release. Case II generally
The mechanism of drug release from the refers to the erosion of the polymeric chain,
tablet matrices was studied by fitting the and anomalous transport (Non-Fickian) refers
release data into the zero-order, first-order to a combination of both diffusion and
and Higuchi kinetic equations [18]: erosion controlled drug release [20].
Zero order: Qt = Qo + Kot …equation 3 The equation of similarity factor (f2) as
First order: InQt = InQo + K1t ...equation 4
/ proposed by [21] was employed to compare
Higuchi: …equation 5
dissolution between the test polymer and the
These models fail to explain drug release
reference polymers.
mechanism due to swelling (upon hydration) .
, 50 1 ∑ 100
along with gradual erosion of the matrix.
Therefore, the dissolution data was also fitted … equation 7
to the well-known exponential equation Where, n = number of observations made
Rt = average percentage drug dissolved from
(Korsmeyer equation), which is often used to
reference formulation
describe the drug release behaviour from Tt = average percentage drug dissolved from test
polymeric systems [19]: formulation
Log (Mt/Mf) = Log k + n Log t equation 6 Stability testing
Where, Mt is the amount of drug release at Representative formulations were selected for
time t; Mf is the amount of drug release after stability testing, according to the USP (1999)
infinite time; k is a release rate constant

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guidelines. The formulations were kept in is released after 120 minutes. The addition of
open amber containers in a stability chamber grewia gum reduces the initial surface erosion
(Firlabo, U.K.) at 25oC and relative humidity of CMC, gum arabic and HPMC and the burst
of 60% and sampled after 0, 15, 30, 45 and 60 effect is eliminated (fig. 2). Consequently all
days for evaluation of appearance and drug the binary composite matrix tablets did not
content. show a burst effect, mimicking the release
Statistical Analysis profile from the more hydrophobic ethyl
The data was subjected to ANOVA using the cellulose matrices [26].
software Instat (GraphPad, San Diego, CA). 100
90
RESULTS AND DISCUSSION
80
Powder characterisation
The moisture content and the flow parameters 70

Percent cimetidine released

of the powder blends are presented in table 3. 60
The moisture content of all powders and 50
blends was between 6.80 and 8.62%. The 40
powder blends for all the formulations 30 Grewia
showed an angle of repose of between 30.0- gum Arabic
20 CMC
32.7o indicating ‘good’ to ‘passable’ flow HPMC
10
behaviour [22, 23]. The upper limit of this Ethyl cellulose
angle (i.e. 42o) is considered a good working 0
0 200 400 600 800
range for most pharmaceutical granules and
powders [24]. Added glidant improves flow Time (min)
when Hausner ratio is between 1.25 and 1.5 Fig 1: Release profiles of cimetidine from the single
polymer matrices containing 40% w/w of grewia, gum
[23] and in order to standardise formulations arabic, CMC, HPMC or ethyl cellulose in phosphate
and allow comparisons on a weight for weight buffer (pH 7.2) solution at 37± 1oC (n=3, mean ± s.d.)
basis, the amount of colloidal silicon dioxide
was maintained at 2.9% w/w. 100
90 Grewia/gum Arabic
Tablet properties (1:1)
The properties of the directly compressed 80 Grewia/HPMC (1:1)
Percent cimetidine released

cimetidine tablet formulations are shown in 70

table 4. The tablets were of good mechanical 60
strength. Tablet friability was low except for 50
gum arabic and CMC single polymer matrices 40
which may be attributable to lamination of 30
some of the tablets in the case of gum arabic 20
matrices and chipping in the case of CMC 10
matrices. Drug content was between 99 to 0
107%. Weight and content variation between 0 200 400 600 800
tablets of the same batch was minimal and Time (min)
within acceptable range as defined in the BP.
In vitro drug release Fig 2: Release profiles of cimetidine from the binary
composite matrices of grewia/gum Arabic (1:1),
The drug release from the single polymer grewia/CMC (1:1), grewia/HPMC (1:1), or
matrices and binary composite matrices of grewia/ethyl cellulose (1:1) in phosphate buffer (pH
cimetidine are shown in fig.1 and 2 7.2) solution at 37± 1oC (n=3, mean ± s.d.)
respectively. The single polymer matrices of
gum arabic, CMC and HPMC (fig. 1) showed The time taken for 50% of drug to be released
a burst effect releasing an amount of drug from the polymer matrices (t50) and the %
ranging between 20 to 50% within the first 60 cimetidine released after 12 hours are shown
minutes potentially due to initial surface in table 5. The single polymer matrices of
erosion [25]. When ethyl cellulose or grewia ethyl cellulose have the longest t50 (663.33
gums are used individually, only 16% of drug minutes) followed by grewia gum single

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polymer matrices with a t50 of 465.0 minutes. released 100% of the drug at the end of 12
There was no significant difference between hours (fig. 2).
the t50 of grewia gum and gum arabic single There was evidence of synergism between
polymer matrices (P>0.05). It can be grewia gum and HPMC when used as binary
concluded that the order of sustained release composite matrices for the release of
of cimetidine from the single polymer matrix cimetidine. The binary matrix tablets of
tablets based on the t50 is: Ethyl cellulose > grewia gum and HPMC (1:1) had a t50 of
grewia gum = gum arabic > HPMC > CMC. about 521 minutes which was higher than the
The CMC single polymer matrices gave the t50 of either grewia gum or HPMC single
lowest t50 of 65 minutes indicating the least polymer matrix tablets.
ability to delay the release of cimetidine.
Only the CMC single polymer matrices

Table 3: Some properties of powder blends for cimetidine matrix tablets

Formulation Moisture content Angle of repose Hausner ratio
(%) (o )
Grewia 8.5±0.5 30.2±1.3 1.5±0.07
Gum arabic 8.6±0.6 30.1±1.4 1.2±0.04
Ethyl cellulose 7.1±0.4 32.7±1.3 1.5±0.01
HPMC 7.4±0.5 32.2±1.1 1.3±0.01
CMC 7.7±0.8 30.3±1.7 1.1±0.04
Grewia/Gum arabic (1:1) 7.6±0.5 30.0±0.7 1.2±0.06
Grewia/Ethyl cellulose (1:1) 8.0±0.8 31.7±1.2 1.4±0.03
Grewia/HPMC (1:1) 6.8±1.0 30.3±0.8 1.5±0.04
Grewia/CMC (1:1) 7.6±0.8 30.5±0.7 1.3±0.03

Table 4: Some properties of cimetidine matrix tablets

Formulation Weight mg) Thickness(mm) Mechanical Friability Drug content
(n=20) (n=10) strength (N) (%) (mg)
Grewia 531.0±0.01 3.6±0.04 84.2±1.5 0.7±0.3 253.1±0.01
Gum arabic 565.0±0.01 3.7±0.13 72.2±2.3 7.6±7.5 269.2±0.00
Ethyl cellulose 544.0±0.01 3.7±0.05 91.0±1.9 0.7±0.3 249.7±0.00
HPMC 569.5±0.01 3.7±0.04 74.6±2.8 0.8±0.2 247.8±0.00
CMC 520.5±0.02 3.7±0.04 66.2±3.6 1.9±0.6 250.3±0.00
Grewia/Gum arabic (1:1) 520.5±0.01 3.4±0.05 84.2±2.9 0.6±0.4 252.5±0.00
Grewia/Ethyl cellulose (1:1) 517.0±0.02 3.6±0.05 88.6±8.2 0.6±0.6 253.5±0.00
Grewia/HPMC(1:1) 534.0±0.01 3.4±0.05 81.4±5.9 0.5±0.5 249.2±0.01
Grewia/CMC (1:1) 518.5±0.01 3.5±0.05 74.6±2.7 0.5±0.5 251.4±0.00

Table 5: Time for 50% cimetidine release (t50) and % cimetidine release from single polymer or binary
matrices after 12 hours in phosphate buffer (pH 7.2), (n=3, mean±s.d.)
Formulation t50(min) % release (12h)
Grewia 465.0±69.5 65.4±3.6
Gum arabic 356.7±67.5 71.3±2.9
CMC 65.0±20.0 100.0±0.4
HPMC 310.0±43.6 76.4±4.1
Ethyl cellulose 663.3±30.6 53.0±2.4
Grewia/gum arabic (1:1) 356.7±5.8 73.5±0.7
Grewia/CMC (1:1) 316.0±2.0 88.7±2.2
Grewia/HPMC (1:1) 521.7±20.2 65.9±1.5
Grewia/ethyl cellulose (1:1) 398.3±28.4 71.8±1.1

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Swelling and erosion release exponent n, of 0.73 indicative of an

Swelling and erosion of the single polymer anomalous or non-Fickian drug release
matrices and the binary composite matrices mechanism except HPMC which showed a
are shown in fig. 3 and 4 respectively. The Fickian release mechanism with best fit to the
results show that swelling and erosion occur Higuchi release model. The hydrophilic
simultaneously for all the matrix tablet polymers such as HPMC, CMC and grewia
formulations. The degree of erosion was gum swell to form gel layers which gradually
higher for HPMC and CMC single polymer dissolve or erode. Drug release from such
matrices. When swelling and erosion of hydrophilic matrices is attributable to relative
matrix tablets occur simultaneously, a contributions of drug diffusion, polymer
constant release of drug can be expected from relaxation and matrix erosion [29]. The
the matrices [27]. This is because increase in release exponent, n, from CMC matrices was
path length which occurs as a result of 1.12, indicative of super case II release. Drug
swelling is compensated for by the transport was primarily by erosion of the
continuous erosion of the matrix that occurs tablet matrix. This is supported by data from
simultaneously [28]. swelling and erosion experiments (fig. 3b)
The very low water uptake of ethyl cellulose which showed CMC matrices exhibited the
matrices is attributable to the hydrophobic highest degree of erosion.
nature of the ethyl cellulose matrices. Grewia a.
gum has the highest capacity for water uptake 400
Grewia
of all the single polymer matrices studied but gum Arabic
erosion of the grewia gum single polymer
Water uptake (%)

300 HPMC
matrices was similar to ethyl cellulose. This Ethyl cellulose
CMC
indicates that the capacity of the gum to 200
ingress water is much higher than the rate or
extent of erosion of the matrices.
100
Consequently, drug release from grewia gum
matrices is predominantly by diffusion across
the swollen matrices. The low erosion of the 0

matrices may be attributable to the fact that 0 100 200 300 400 500 600

grewia gum does not dissolve upon swelling Time (minutes)

or hydration in aqueous media [13]. b.
100
Drug release kinetics
The kinetics of drug release form the single grewia
80
polymer and binary composite matrices were
plotted according to the various kinetic law
Erosion (%)

gum Arabic
60
equations and the regression coefficients and
the release exponent based on the Korsmeyer- 40
Peppas model are shown in table 6.
The grewia gum single polymer matrices 20
showed correlation with the Higuchi and
Korsmeyer-Peppas model (P>0.05). The 0
release exponent, n is indicative of non- 0 100 200 300 400 500 600
Fickian or anomalous transport (table 6). All Time (minutes)
other single polymer matrices also best fitted Fig. 3: Water uptake (a) and erosion (b), of single
polymer matrices of cimetidine containing grewia,
a non-Fickian transport of drug. This gum arabic, HPMC, CMC or ethyl cellulose in
indicates that drug release from the single phosphate buffer (pH 7.2), (n=2, mean).
polymer matrices of grewia gum is diffusion
controlled with the profile attaining a near For all the binary composite matrices, similar
zero order release. The relative contributions mechanism of drug transport predominates.
of both swelling and erosion to drug release The anomalous behaviour seen is attributable
for the grewia gum matrices produced a to relative contributions of drug diffusion,

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polymer relaxation and matrix erosion [29, drug transport. While drug transport across
30, 31]. CMC matrices was predominantly erosion
controlled, drug transport across grewia gum
a. matrices was predominantly by swelling and
300
diffusion across the matrix. The order of
250 similarity of the reference single polymer
matrices to grewia gum single polymer matrix
Water uptake (%)

200 tablets is ethyl cellulose > gum arabic >

150
HPMC > CMC. It can be seen from the
results that while grewia gum single polymer
100 Grewia/gum arabic (1:1) matrices are most similar to ethyl cellulose
Grewia/HPMC (1:1)
50 Grewia/ethyl cellulose (1:1)
matrices based on the similarity factor f2, the
Grewia/CMC (1:1) gum was most similar to gum arabic based on
0 t50. In combination the order is similar with
0 100 200 300 400 500 600 the presence of grewia gum exerting the
Time (minutes) major influence. It will appear that similarity
b. between grewia gum and the reference
80 polymers was greatly determined by the
Grewia/gum arabic (1:1) degree of erosion of the matrices.
60
Consequently, single polymer matrices with
Grewia/HPMC (1:1)
the lowest degree of erosion of the matrices
Erosion (%)

exhibited the highest degree of similarity.

40

Stability of Cimetidine tablet formulations

20 Cimetidine matrix tablet batches did not show
any change in appearance even after 60 days
storage at room temperature and 60% relative
0
humidity. . There was no significant
0 100 200 300 400 500 600
difference (P > 0.05) in the drug content of
Time (minutes) any matrix tablets at the end of the 60 days
Fig. 4: Water uptake (a) and erosion (b) with time of (table 7). Grewia gum matrices for controlled
binary composite matrices of grewia and gum arabic,
HPMC, CMC or ethyl cellulose (ratio 1:1) in release of cimetidine demonstrated good
phosphate buffer (pH 7.2), (n=2, mean). product stability over the duration of the
study, similar to the commercially available
The similarity factor (f2) was used to compare excipients. The significance of this result to
drug release from the polymer matrices (table grewia polysaccharide gum is that the gum
6). The test formulation was the grewia gum may not interfere with the stability of APIs
single polymer matrix formulation. An f2 when used as an excipient in tablet
value of 100 suggests that the test and formulation.
reference profiles are identical. The CONCLUSION
dissimilarity between release profiles Grewia polysaccharide gum was capable of
increases as the f2 value decreases. The prolonging the release of cimetidine from
highest dissimilarity exists between the matrix tablets of the gum for up to 12 hours.
profiles of grewia gum and CMC single Physicochemical properties such as high
polymer matrices (f2 =15.31), while the molecular weight, low solubility, high
highest similarity is seen between the profiles viscosity and long swelling time [13] enable
of grewia gum single polymer matrices and grewia polysaccharide gum to function as a
the binary matrices of grewia/ethyl cellulose suitable insoluble polymer matrix for the
(1:1) with f2 of 70.95. The dissimilarity release of active medicaments. This strong
between grewia gum and CMC single sustained-release potential of grewia
polymer matrices may be attributable to the polysaccharide gum was superior to
relative contribution of swelling or erosion to hydrophilic matrices of HPMC, CMC and

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Table 6: Kinetic parameters of cimetidine matrix tablets

Formulation Release Korsmeye Zero- First- Higuchi Similarity
exponent r-Peppas order order model (r2) factor (f2)
(n) (r2) kinetic kinetic
(r2) (r2)
Grewia 0.73±0.04 0.99±0.00 0.96±0.01 0.60±0.02 0.98±0.01 -
CMC 1.12±0.39 0.89±0.05 0.55±0.06 0.28±0.02 0.76±0.10 15.3±0.3
Gum arabic 0.59±0.02 0.96±0.00 0.93±0.01 0.53±0.09 0.99±0.00 54.4±11.9
HPMC 0.47±0.02 0.95±0.02 0.92±0.01 0.41±0.01 0.99±0.002 46.9±5.8
Ethyl cellulose 0.86±0.01 0.91±0.04 0.91±0.03 0.49±0.05 0.98±0.01 57.0±8.6
Grewia/CMC (1:1) 0.79±0.02 0.99±0.01 0.97±0.00 0.65±0.01 0.96±0.01 42.7±5.0
Grewia/gum arabic (1:1) 0.73±0.01 0.98±0.02 0.97±0.00 0.62±0.02 0.97±0.01 61.6±8.2
Grewia/HPMC (1:1) 0.74±0.01 0.99±0.01 0.99±0.00 0.66±0.02 0.96±0.01 64.8±5.8
grewia/ethyl cellulose (1:1) 0.77±0.01 0.99±0.01 0.98±0.01 0.63±0.01 0.98±0.00 71.0±10.1

Table 7: Effect of temperature and relative humidity on drug content (%) stability of cimetidine matrices
(n=5, mean ± s.d.)
Formulation Day 0 Day 15 Day 30 Day 45 Day 60
Grewia 101.1±2.0 99.3±2.1 99.5±1.3 98.8±1.1 98.5±0.6
Gum arabic 107.9±1.2 106.9±1.3 106.4±1.4 106.3±1.0 106.4±1.2
Ethyl cellulose 100.1±1.2 99.2±2.0 98.1±2.4 100.1±1.2 99.0±1.1
HPMC 99.2±1.7 98.2±2.8 98.0±2.9 97.7±2.9 98.8±1.6
CMC 100.6±1.6 100.4±1.5 99.7±1.3 99.4±1.3 99.1±1.5

gum arabic. The release of drug from the erosion and drug release from hydrophilic
grewia polysaccharide gum matrices was natural gum mini-matrix formulations. Eur J.
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