International Journal of Pharmacy and Biological Sciences-IJPBSTM (2020) 10 (2): 238-248

Online ISSN: 2230-7605, Print ISSN: 2321-3272

Research Article | Pharmaceutical Sciences | Open Access | MCI Approved

Formulation and Evaluation of Matrix

System for Simultaneous Sustained
Release of Diclofenac Sodium and
Tizanidine Hydrochloride
Nilesh Jain*1, Jobin Abraham2, Ruchi Jain2 and Surendra
Kumar Jain2
1Sagar Institute of Research Technology and Science-Pharmacy, Near
ISRO, Bhopal
2Sagar Institute of Research and Technology-Pharmacy, Ayodhya

Bypass Road, Bhopal

Received: 10 Jan 2020 / Accepted: 8 March 2020 / Published online: 01 April 2020
*Corresponding Author Email: [email protected]

Abstract
The aim of the present investigation was to formulate and evaluate matrix tablets system for
diclofenac sodium and tizanidine to achieve an extended drug release with reduced frequency
of drug administration, reduced side effects and improved patient compliance. In the present
study, matrix tablets were formulated in which sustained release layer was prepared by using
synthetic polymer like ethyl cellulose by wet granulation method. The tablets were evaluated
for Physico-Chemical Properties such as Hardness, Friability, Thickness Weight variation, Drug
content uniformity. The In vitro release studies were performed in 0.1 N HCl for first two hr. and
in 6.8 pH Phosphate buffer up to 12 hr. It was observed that matrix tablets having formulation
code F1-F12 which contained 50% ethyl cellulose were successfully sustained the release of drug
up to 12hr. FT-IR studies revealed that there was no interaction between the drug and polymer
used in the study.
Keywords
DICS-diclofenac sodium, TIZH-tizanidine hydrochloride Sustained release, Ethyl cellulose
*****

INTRODUCTION • The physical state of drug.

All the pharmaceutical products formulated for • The matrix shape and alteration in volume as a
systemic delivery via the oral route of administration function of time.
irrespective of the mode of delivery (immediate, • The route of administration.
sustained or controlled release) and the design of • The release kinetic model.
dosage forms (either solid dispersion or liquid) must DICS and TIZH have been used in combination
be developed within the intrinsic characteristics of because there are minor differences in the
gastrointestinal physiology, pharmacokinetics and pharmacokinetics of both the drugs. These two drugs
pharmacodynamics as formulation design is essential are commonly prescribed by the doctors for the relief
to achieve a systemic approach to the successful of pain and inflammations. Sustained release
development of an oral dosage form. 1 formulation of DICS and TIZH will be able to prolong
To define matrix, it is necessary to know the the release of the both the drugs and reduce the
characters that differentiate it from other controlled fluctuations in plasma drug concentrations as in case
release dosage forms. 2

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of conventional dosage form will thus minimize or Angle of repose

prevent plasma peak-related adverse events and A funnel was fixed at a height approximately of 2-4
allow prolongation of the dosing interval enabling a cm over the platform. The loose powder was slowly
once or twice daily administration with inherent passed along the wall of funnel, till the cone of the
benefits in terms of patient compliance. Sustained- powder formed.
release oral delivery systems are designed to achieve tan-1 θ = h / r
therapeutically effective concentrations of drug in θ = tan –1 h / r
the systemic circulation over an extended period of Where,
time, thus achieving better patient compliance and θ = Angle of repose.
allowing a reduction of both the total dose of drug h = Height.
administered and the incidence of adverse side r = Radius
effects. Among the different approaches studied UV-VIS spectrophotometric Method for DICS and
with this aim, matrix systems appear as one of the TIZH
most attractive; from both the economic, as well as, Selection of solvent Study of spectra and selection
process development and scale-up point of view3. of analytical wavelengths
The solvent phosphate buffer pH 6.8 was used for the
\MATERIALS AND METHOD preparation. An amount equivalent to 10 mg of the
Diclofenac sodium (DICS) and Tizanidine reference standard DICS and TIZH was added to 100
hydrochloride (TIZH) was obtained as gift sample mL volumetric flasks separately. DICS and TIZH was
from Lupin Research Park, Pune. Methocel- K4M and dissolved separately in around 50 mL Phosphate
Avicel PH 101,102 was obtained as gift sample from Buffer Saline (PBS) pH 6.8 in a 100 mL volumetric
Colorcon Pvt. Ltd, Goa. Chitosan was obtained as gift flask with vigorous shaking followed by
sample from Panecea Biotech, Mumbai. Guar gum, ultrasonication for about 5 minutes. The volume was
Potassium dihydrogen phosphate (AR), Methanol made up to the mark with the same solvent to obtain
(AR), Methanol (HPLC grade), Water (HPLC grade) standard stock solutions of concentration, 100 µg/
were given by SIRT college from company Merck mL of both drugs. By appropriate dilution of the
India Ltd., Mumbai. Sodium alginate, sodium standard stock solution, working standard solutions
hydroxide, magnesium stearate, xanthan gum, ethyl of suitable concentrations (10 µg/ mL) of DICS and
cellulose was given by SIRT college from Loba Chemie TIZH were prepared separately. The standard
Pvt. Ltd., Mumbai. All other chemicals and reagents solutions were then scanned in the spectrum mode
used were of “analytical reagents” (AR) of the instrument from 400 nm to 200 nm to
Micromeritic characterization of drug 4 determine λmax (wavelength maximum) for both DICS
Loose bulk density and Tapped bulk density and TIZH.
10 gm sample was carefully introduced into a 25 mL Study of Beers-Lambert’s Law
graduated cylinder. The volume occupied by the Preparation of standard stock solutions:
powder was recorded and bulk density then Standard stock solutions (100µg/mL) of DICS and
calculated, and the cylinder was dropped at 2-second TIZH were prepared separately. 10 mg of drug was
intervals onto a hard wood surface 100 times from a dissolved in 50 mL of distilled water in 100 mL
height of 1 inch volumetric flask with shaking and then volume was
Df = M / Vp made up to the mark with same solvent.
Do = M / Vp Preparation of standard calibration curves and
Where, selection of analytical concentration ranges: For
Df = Loose bulk density DICS, appropriate aliquots of standard stock solution
M = Weight of samples in grams of the drug were transferred to a series of 10 mL
Vp = Final volume of powder in cm 3 volumetric flasks. The volume was made up to the
Do = Tapped bulk density. mark with PBS pH 6.8 to obtain working standard
Compressibility Index and Hausner’s ratio solutions of concentrations of 5, 10, 15, 20….35
The compressibility index and the Hausner ratio are µg/mL. TIZH appropriate aliquots of standard stock
determined by measuring both the bulk density and solution of the drug were transferred to a series of
the tapped density of a powder. 10 mL volumetric flasks. The volume was made up to
Compressibility= (tapped- loose bulk density)/loose the mark with PBS pH 6.8 to obtain working standard
bulk density*100 solutions of concentrations of 3, 6, 9, 12, 15…21
Hausner’s ratio=tapped density/loosed bulk density µg/mL. Similarly, for the absorbance of three
replicates of the working standard solutions of each
concentration were measured at the selected

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analytical wavelengths. The standard calibration Method Development by HPLC for DICS and TIZH
curves of absorbance vs. concentration were plotted. Selection of mobile phase 8
Multicomponent detection analytical method 5,6 The criteria employed for selection of particular
(Simultaneous Equation Method) solvent system for the analysis was cost, time
In this method absorbance were measured at λ max (λ1 required for analysis, sensitivity of the assay and
and λ2) of both the drugs, i.e. DICS (10 µg/mL) and solvent noise for the analysis of DICS and TIZH from
TIZH (10 µg/mL). Two equations were constructed tablet formulation. various ratios of acetonitrile
based upon the fact that at λ1 and λ2, the absorbance (ACN): water (HPLC grade) 25mM phosphate buffer
of the mixture is the sum of the individual pH 7 were tried to develop a sensitive and accurate
absorbance of DICS and TIZH. method like.
CDICS = A2ay1-A1ay2 / ax2ay1-ax1ay2CTIZH = A1ax2-A2ax1 1. ACN: Water (70: 30 v/v)
/ ax2ay1-ax1ay2 2. ACN: Water (50: 50 v/v)
Where, A1 and A2 are absorbance of mixture at λ1 and Then, phosphate buffer pH 7 was used instead of
λ2, ax1 and ax2 are absorptivities of DICS at λ 1 and water.
λ2 respectively. ay 1 and ay2 are absorptivities of TIZH 1. ACN: 25mM phosphate buffer pH 7 (70: 30 v/v)
at λ1 and λ2 respectively and CDiclo and CTiza are 2. ACN: 25mM phosphate buffer pH 7 (50: 50 v/v)
concentrations of DICS and TIZH respectively.
Determination of solubility of DICS and TIZH Preparation of standard stock solutions and
Saturation solubility of DICS and TIZH was Selection of analytical Wavelength8
determined in 0.1 N HCl, pH 1.2, pH 4.5 buffer and Standard stock solutions (100µg/mL) of DICS and
pH 6.8 phosphate buffer solutions. All media were TIZH were prepared separately. Dissolve 10 mg of
prepared and excess quantity of DICS and TIZH was drug in 100 mL of volumetric flask with 50 mL of
individually added to it and kept for shaking on acetonitrile: water (HPLC grade) (1:1v/v) with
mechanical shaker for 48 hrs. After 48 hrs of shaking, shaking and then volume was made up to the mark
1 mL of aliquot was taken out from each sample and with same solution.
filtered through whatman filter paper (45µm). By appropriate dilution of the standard stock
Filtrates were diluted with respective solution (i.e. solution with mobile phase, various concentrations
0.1 N HCl, pH 1.2, pH 4.5 buffer and pH 6.8 phosphate of DICS and TIZH were prepared separately. Their
buffer). Absorbance was measured and solubility was spectra were obtained using the double beam UV
determined for both the drugs. visible spectrophotometer (Table 1-4).

Table No.1 Concentration and absorbance values for DICS in PBS pH 6.8
Sr. No. Concentration (µg/ml) Absorbance at 276.2 nm*
1 0 0
2 5 0.1645
3 10 0.2917
4 15 0.4469
5 20 0.6141
6 25 0.7359
7 30 0.8553
8 35 1.015
R2 0.999
Slope 34.7718
Intercept -0.4222

Table No.2 Concentration and absorbance values for TIZH in PBS pH 6.8
Sr. No. Concentration (µg/ml) Absorbance at 321 nm*
1 0 0
2 3 0.1393
3 6 0.290184
4 9 0.41925
5 12 0.5975
6 15 0.747
7 18 0.881
8 21 0

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R2 0.999
Slope 34.7718
Intercept -0.4222

Table No.3 Concentration and area value for DICS

Sr. No. Concentration (µg/ml) AUC at 220.0 nm*
1 0 0
2 6 170493
3 8 233270
4 10 285990
5 12 338344
6 14 384983
7 16 438985
R2 0.998
Slope 27403
Intercept 6207

Table No.4 Concentration and area value for DICS

Sr. No. Concentration (µg/ml) AUC at 220.0 nm*
1 0 0
2 2 113455
3 4 197389
4 6 286789
5 8 370610
6 10 449783
7 12 539245
R2 0.997
Slope 43993
Intercept 15652

Fig. No. 1 UV spectra of DICS (10µg/mL) in PBS pH 6.8 (λmax=276.2nm)

Fig. No. 2 UV spectra of TIZH (10µg/mL) in PBS pH 6.8 (λmax=320nm)

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1.2

ABSORBANCE
0.8

0.6

0.4

0.2

0
0 10 20 30 40

CONCENTRATION

Fig. No. 3 Calibration Curve of DICS

1.2

1
ABSORBANCE

0.8

0.6

0.4

0.2

0
0 10 20 30 40
CONCENTRATION

Fig. No. 4 Calibration Curve of TIZH

Fig. No. 5 Overlay UV spectra of DICS and TIZH in PBS pH 6.8

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Fig. No. 6 Chromatogram of Pure DICS

CALIBRATION CURVE OF DICLOFENAC

600000
500000
AUC AT 220 nm

400000
300000
200000
100000
0
0 2 4 6 8 10 12 14
CONCENTRATION

Fig. No. 7 Calibration curve of DICS

Calibration curve of TIZH

600000
500000
AUC at 220 nm

400000
300000
200000
100000
0
0 2 4 6 8 10 12 14
CONCENTRATION

Fig. No. 8 Calibration curve of TIZH

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Fig. No. 9 Chromatogram Of TIZH

Preparation of Standard Calibration curves of DICS and 2.5-12.5 µg/mL for TIZH. Triplicate dilutions of
and TIZH by HPLC Method (Table 3 and Table 4) each concentration of drug were prepared. From
Chromatographic conditions8 these triplicate solutions, 25μl injection of each
The chromatographic column used was a reverse concentration of drug was injected into the HPLC
phase 4.6µ250 mm Hypersil C 18 HPLC column with system. Evaluation of both drugs was performed with
5µm (particles) packing. The column and the HPLC the UV detector set at 220 nm. Peak area was
system were kept at ambient conditions. The mobile recorded and working calibration curves were
phase was ACN: Phosphate buffer pH 7.0 (50:50 v/v) plotted separately with peak area Vs the respective
delivered at a flow rate of 1.0 mL/min. The injection concentration of DICS and TIZH.
volume was 25 µL. Elute was analyzed by a UV Formulation Development
detector set at 220 nm. For preparation of standard All of the formulations contained 100 mg DICS, 6.86
calibration curve, appropriate aliquots were pipette mg of TIZH, 1% (w/w) magnesium stearate,
out from stock solutions into a series of 10 mL microcrystalline cellulose (MCC) and different
volumetric flasks. The volume was made up to the amounts of various polymers. The composition of
mark with mobile phase to obtain a set of solutions various formulations is listed in Table 5 and 6.
of DICS having concentration range 2-10 µg/mL each

Table No.5 Composition of formulations

Formulations F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
DICS 100 100 100 100 100 100 100 100 100 100
TIZH 6.86 6.86 6.86 6.86 6.86 6.86 6.86 6.86 6.86 6.86
HPMCK4 M 30 45 60 90 120 150 - - - -
HPMCK15 M - - - - - - 90 120 150 -
HPMCK100 M - - - - - - - - - 90
Avical 102 145.14 130.14 100.14 70.14 40.14 100.14 70.14 40.14 100.14 -
Mg. Stearate 3 3 3 3 3 3 3 3 3 3
Total weight 300 300 300 300 300 300 300 300 300 300
(All quantities are in mg)

Table No.6 Composition of formulations

Formulations F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
DICS 100 100 100 100 100 100 100 100 100 100
TIZH 6.86 6.86 6.86 6.86 6.86 6.86 6.86 6.86 6.86 6.86
Guar gum 15 30 90 200 30 - - - - -
Chitosan - - - - - 60 60 30 - -
Sodium Alginate 3 3 3 3 3 60 30 60 - -
Xanthan gum - - - -- - - - - 30 60

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Ethyl cellulose - - - -- - - - - 30 60
Avical 102 160.14 70.14 100.14 100.14 130.14 70.14
Avicel 101 175.14 160.14 100.14 100.14 - - - - - -
Mg.stearate 3 3 3 3 3 3 3 3 3 3
Total weight 300 300 300 300 300 300 300 300 300 300
(All quantities are in mg)

Preparation of Matrix Tablets Content uniformity

Various formulations of tablets were prepared as For this at least 30 tablets were randomly selected.
shown in Table 5 and 6. The drug powder and other Out of 30 tablets, 10 tablets were crushed into fine
ingredients were passed through an 80-mesh sieve powder and assayed individually.
before mixing. In order to keep the volume and In vitro dissolution studies
surface area of tablets relatively constant, the final The in vitro dissolution studies were performed using
weight of each tablet was maintained at 300 mg. All USP-22 type-II dissolution apparatus at 50 rpm. The
of the formulations contained 100 mg of DICS, 6.86 dissolution medium consisted of phosphate buffer
mg of TIZH (6.86 mg of tizanidine hydrochloride solution pH 6.8 for 12 hours (900 mL), maintained at
equivalent to 6 mg of tizanidine), 1% (w/w) 37°C ± 0.5°C. An aliquot (10 mL) was withdrawn at
magnesium stearate and different amounts of specific time intervals and drug content was
various polymers and Avicel-102. The composition of determined by UV-visible spectrophotometer (UV-
various formulations is listed in Table 5 and 6. DICS, 1700- Shimadzu Japan) at 276.2 nm and at 320 nm
TIZH and other ingredients were weighed, and the for DICS and TIZH respectively by using simultaneous
mixture was then blended with magnesium stearate equation method. At each time of withdrawal, 10 mL
(1% w/w) as lubricant in a polybag, and then of fresh corresponding dissolution medium was
compressed into tablets. All tablets were prepared replaced into the dissolution flask. It was made clear
using six station rotary tablet machine (GMC that none of the ingredients used in the matrix
Mumbai) equipped with standard concave punches formulations interfered with the assay. The release
of 9-mmdiameter. studies were conducted in triplicate.
Evaluation parameters for tablets6,7 Matrix integrity
Hardness Matrix integrity was observed throughout in vitro
Although hardness test is not an official, tablet dissolution studies and the swollen mass of the
should have sufficient handling during packing and tablets whether remains intact or not was checked.
transportation. Hardness of tablet was measured Dissolution kinetic study 8,9
using Monsanto hardness tester. The hardness of 6 Various mathematical models like; Zero-order
tablets, from each batch was determined and mean model, First-order model, Higuchi (Matrix) model,
hardness was taken into account, which was Hixson and Crowell cube-root equation and
expressed in kg/cm2. Korsmeyer-Peppas Model were evaluated with
Weight variation test respect to the dissolution profiles of the optimized
Weigh 20 tablets individually, calculating the average formulations of HPMC K4M and guar gum. PCP disso-
weight and compare the individual tablet weight software was used to fit models to dissolution
with respect to the USP weight variation test profiles.
Friability Stability studies
Friability test is performed to assess the effect of The stability of the active component must be major
friction and shocks, which may often cause tablet to criteria in determining their acceptance or rejection.
chip, cap or break. Roche friabilator was used for the During the stability studies the product is exposed to
purpose. normal conditions of temperature and humidity.
The percentage friability was measured using the However, the studies will take a longer time and
formula, hence it would be convenient to carry out the
Where, accelerated stability studies where the product is
% F = friability in percentage Wo = Initial weight of stored under extreme conditions of temperature.
tablet
W = weight of tablets after revolution RESULTS AND DISCUSSION
Thickness Micromeritic characterization of drug:
The thickness of the tablet was measured using Table 2 shows the relationship between %
Vernier caliper. Thickness of five tablets from each compressibility and flow property of powder. From
batch was measured and mean was calculated

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micromeritic characteristics study it was found that Evaluation of tablets

both the DICS and TIZH have good flow properties. Hardness of tablets of each formulation was
UV-VIS spectrophotometric Method for DICS and measured and was found in the range of 5-8 kg/cm2.
TIZH: - Average weight of the tablet was found to be 300 ± 3
UV spectrum for DICS and TIZH are shown in Figure 1 mg for all formulations. Percentage weight loss of the
and 2 respectively. tablets of each formulation was measured and was
Study of Beers-Lambert’s Law: calibration curve for found to be less than 1% for all the formulations.
DICS Diameter of formulations was found to be 9 ± 0.05
The calibration curve for DICS and TIZN in PBS pH 6.8 mm. Thickness was found to be 5 ± 0.2 mm for all the
is shown in Figure 3and 4 and Table no 3,4. The graph formulations. The content uniformity for all tablet
of absorbance vs. concentration for DICS was found formulations was found to be between 98.80 % to
to be linear in the concentration range of 5-35 μg/ml 100.40 % for DICS and 98.70 % to 100.20 % for TIZH.
and 3-21 μg/ml at 276.2 nm and 320 nm. The r 2 of All parameter was shown on table 7
the calibration curve was found to be 0.999. Matrix integrity
Multicomponent detection for DICS and TIZH Integrity of a tablet matrices were studied at time
(Simultaneous Equation Method) interval of 1, 2, 4, 6, 8, and 12hr by visual
In this method absorbances were measured at λ max observation. Matrices of tablets were found to have
(λ1 and λ2) of both the drugs, i.e. diclofenac at λmax of good integrity till the end of 12 hr. dissolution study,
276.2 nm and tizanidine at λ max of 320 nm. and as tablet matrices got eroded at controlled rate
Absorbance of DICS and TIZN was found to be 0.4849 it was able to release both the drugs in controlled
and 0.07465 at 276.2nm and at 320 nm 0.01035 and manner.
0.794 and Figure 5 shows the overlay spectra of DICS Dissolution kinetic study
and TIZH. Kinetics treatment
Determination of solubility Table 8 shows the Kinetics treatment for the
The solubility data for DICS and TIZH as observed in optimized formulations. From drug release kinetic
0.1 N HCl and buffers of pH values 4.5 and 6.8 was model study, it was found that the matrix (Higuchi)
found to be 0.069, 3.803 and 18.9. model was best fitted for the optimized formulation
HPLC method development F1 and F11, for both the drugs i.e., DICS and TIZH.
Calibration curve of diclofenac sodium and From the regression value (R 2) it was found that
tizanidine hydrochloride by HPLC Higuchi square root model was best fitted for both
The chromatogram of pure diclofenac sodium and the formulations F1 and F11.
tizanidine hydrochloride at concentration 10 µg/ml Stability study
and 2 µg/ml. The standard calibration curve and Formulation F1 and F11 were kept for stability study,
table for DICS and TIZH is shown Figure 6 and 7, Table tablets were packed in PVC –PVDC coated aluminum
5 and 6 respectively. A linear correlation was found - aluminum strip pack of 10 tablets and were kept at
between area under the curve and concentration in 45oC and 75% RH for 3 months. These formulations
the ranges 6 to 16 µg/ml and 2 to 12 µg/ml. The were evaluated for following parameters after
retention time was observed as 9.15 min and 5.66 stability study.
min. The r2 of the calibration curve was found to be
0.998 and 0.996.

Table No.7 Micromeritic Characterization of Drugs

Sr. No. Parameters Result of DICS Result of TIZH
1 Loose bulk density 0.43±0.03g/cm3 0.51±0.04g/cm3
2 Tapped density 0.49±0.04g/cm3 0.58±0.06g/cm3
3 Carr's Index 13.95±0.05 % 13.72±0.03 %
4 Hausner's ratio 1.139 1.137
5 Angle of Repose 30o 18’ 28o 34’

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Table No.8 Evaluation Parameter of Tablets

Hardness
Formulation thickness(mm)* variation (mg)* (%)* DICS TIZH
(kg/cm2)*
F1 6-7 5±0.10 300 ±2 0.60 ±0.02 99.20±0.20 98.90±0.20
F2 6-7 5±0.10 300 ±2 0.60 ±0.05 99.30±0.10 99.40±0.20
F3 6-7 5±0.10 300 ±1 0.60 ±0.05 98.90±0.20 99.30±0.30
F4 6-7 5±0.20 300 ±2 0.50 ±0.06 100.20±.20 98.70±0.30
F5 6-7 5±0.20 300 ±1 0.50 ±0.06 99.60±0.30 100.20±0.20
F6 6-7 5±0.20 300 ±2 0.46±0.04 99.45±0.20 99.80±0.40
F7 6-7 5±0.10 300 ±1 0.41 ±0.03 98.80±0.30 100.10±0.10
F8 6-7 5±0.20 300 ±2 0.50 ±0.06 99.20±0.10 98.70±0.30
F9 6-7 5±0.20 300 ±2 0.66 ±0.04 99.40±0.40 98.80±0.20
F10 6-7 5±0.10 300 ±1 0.61 ±0.04 99.70±0.10 99.20±0.10
F11 7-8 5±0.10 300 ±2 0.61 ±0.05 100.10±0.10 99.90±0.20
F12 7-8 5±0.20 300 ±3 0.56 ±0.03 99.30±0.20 99.70±0.20
F13 7-8 5±0.20 300 ±1 0.46 ±0.03 101.10±0.10 101.20±0.10
F14 5-6 5±0.10 300 ±2 0.51 ±0.06 100.40±0.10 99.60±0.10
F15 6-7 5±0.10 300 ±3 0.54 ±0.04 99.20±0.40 98.90±0.20
F16 5-6 5±0.10 300 ±1 0.41 ±0.04 99.40±0.20 100.20±0.20
F17 5-6 5±0.20 300 ±2 0.61 ±0.04 99.40±0.20 99.80±0.10
F18 5-6 5±0.10 300 ±2 0.66 ±0.03 98.90±0.30 98.70±0.40
F19 6-7 5±0.10 300 ±2 0.51 ±0.04 99.40±0.40 99.70±0.30
F20 6-7 5±0.20 300 ±1 0.60 ±0.03 100.20±0.20 99.70±0.20

Table No.9 In-vitro Drug diffusion kinetic study

S.NO Model Correlation coefficient (R 2)
DICS F1 TIZH F1 DICS F11 TIZH F11
1 Zero order 0.8574 0.8315 0.8582 0.8438
2 First order 0.9257 0.9723 0.8939 0.9638
3 Matrix 0.9989 0.9979 0.9989 0.9987
4 Peppas 0.9975 0.9970 0.9974 0.9976
5 Hixson Crowell 0. 9826 0.9799 0.9781 0.9852

Fig. No. 10 Higuchi square root model study for DICS and TIZH from F1 (HPMC K4M 10%)

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Fig. No. 11 Higuchi square root Model study for DICS and TIZH from F 11 (Guar gum 5%)

CONCLUSION REFRENCES
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ACKNOWLEDGEMENT
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The authors are very much thankful to Surendra absorption: immediate release dosage forms, Pharm
Kumar Jain Director, SIRT College of Pharmacy Res. 15 (1), 11-22.
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International Journal of Pharmacy and Biological Sciences Nilesh Jain* et al 248

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