Vol.2, No.4, 379-387 (2010) Natural Science
http://dx.doi.org/10.4236/ns.2010.24046
Study the effect of formulation variables in the
development of timed-release press-coated
tablets by Taguchi design
Chikkanna Narendra1*, Mayasandra SrinavasaIyengar Srinath2
1Department of Pharmaceutics, Visveswarapura Institute of Pharmaceutical Sciences, Bangalore, India;
2Department of Pharmaceutics, SET’S College of Pharmacy, Dharwad, India
Received 30 November 2009; revised 28 December 2009; accepted 3 February 2010.
ABSTRACT
In this investigation, the effect of formulation
variables on the release properties of timed-
release press-coated tablets was studied using
the Taguchi method of experimental design.
Formulations were prepared based on Taguchi
orthogonal array design with different types of
hydrophilic polymers (X1), varying hydrophilic
polymer/ethyl cellulose ratio (X2), and addition
of magnesium stearate (X3) as independent
variables. The design was quantitatively evalu-
ated by best fit mathematical model. The results
from the statistical analysis revealed that factor
X1, X3 and interaction factors between X1X2 and
X1X3 were found to be significant on the re-
sponse lag time (Y1), where as only factor X1
was found to be significant on the response
percent drug release at 8 hrs (Y2). A numerical
optimization technique by desirability function
was used to optimize the response variables,
each having a different target. Based on the re-
sults of optimization study, HPC was identified
as the most suitable hydrophilic polymer and
incorporation of hydrophobic agent magnesium
stearate, could significantly improve the lag
time of the timed-release press-coated tablet.
Keywords: Press-Coated Tablet; Taguchi Design;
Hydrophilic Polymers; Timed-Release; Hydrophobic
Agents
1. INTRODUCTION
During the recent years timed-release preparations has
received increasing attention, which release the drug
rapidly and completely after a lag time following oral
drug administration. This type of delivery system is not
only rate controlled but also time and /or site controlled
to deliver the drug when it is required. Such time and/or
site controlled formulations has been widely investigated
for a number of diseases and therapies [1,2].
Over a period, many different approached have been
used for delivering the drugs as time and /or site specific
which includes, Timeclock® system [3], Chronotropic®
system [4], Pulsincap® sysem [5], Port® system [6],
Ti m eR x® system [7] and Geomatrix® system [8]. These
systems are developed with intention to meet the needs
of chronopathologies with symptoms mostly recurring at
night time or early morning hours. The principal advan-
tage of Chronotherapeutic drug delivery system includes
consideration of a person’s biological rhythms in deter-
mining the timing and the amount of medication to op-
timize a drug's desired effects and minimize the unde-
sired ones. As a consequence there is reduction of dose
requirement and this likely to improve patient compli-
ance [9].
In spite of the difficulties faced by releasing actives
due to the variable gastrointestinal environment, orally
administered timed-release delivery systems are most
preferred because they offer flexibility in dosage-form
design and are relatively safe. Press-coated tablet com-
posed of an inner core that contains an active pharma-
ceutical ingredient and inert excipients surrounded by an
outer coating layer. The outer coating material may be
compressed onto the inner core as compression coated
which dissolves or erodes or disintegrates slowly to
produce a lag time before the release of active ingredi-
ent.
Several types of hydrophilic polymers have been in-
vestigated as a compression coating material including
hydroxypropylmethylcellulose [10], L-hydroxypropylce-
llulose [11], hydroxyethylcellulose [12], polyethylene-
oxide/polyethyleneglycol [13], and pectin/ hydroxypro-
pylmethylcellulose [14]. Lin et al. [15] studied the effect
of hydrophilic excipients (spray-dried lactose and
HPMC K4M) along with hydrophobic ethylcellulose as
an outer coating shell material and concluded that addi-
tion of hydrophilic excipients can be very useful in con-
trolling the lag time adequately. The effect of hydroxyl-

C. Narendra et al. / Natural Science 2 (2010) 379-387
380
propylmethylcellulose acetate succinate (HPMCAS) and
water soluble/insoluble plasticizers-adsorbent as outer
coating material was reported by Fukui et al. [16] and
the results suggested that the outer shell had a plastic
deformation property due to some interaction between
HPMCAS and water soluble plasticizers-adsorbent and
the same would be useful for colon targeting. In another
study, effect of hydrophobic additives were investigated
and the results indicated that mixing of HPMCAS, mag-
nesium stearate and calcium stearate at appropriate ratio
prolonged the lag time [17].
Design of experiment has been widely used in phar-
maceutical field to study the effect of formulation vari-
ables and their interaction on dependent (response)
variables. [18-20] In the present study an attempt is
made to study the effect of formulation variables with
the aid of Taguchi design to identify the potential con-
tribution of various types of hydrophilic polymers,
varying the hydrophilic/ethylcellulose ratio and presence
and absence of magnesium stearate.
2. MATERIALS AND METHODS
2.1. Materials
Theophylline anhydrous was received as gift sample
from M/s Eros Pharma Pvt. Ltd., Bangalore, India. Hy-
droxypropylmethylcllulose (HPMC, Methocel K100M),
sodium carboxymethylcellulose (NaCMC, HVP), Hy-
droxypropylcellulose (HPC, Klucel® EXF Pharm), Hy-
droxyethylcellulose (HEC, NATROSOL® 250 HX
Pharm) and ethylcellulose (EC, Ethocel® 25cPs) were
supplied by M/s Strides Arco, Labs Ltd., Bangalore, In-
dia as gift samples. Other materials were purchased from
commercial source; magnesium stearate (Loba chemi-
cals, Mumbai, India), polyvinylpyrrolidine (PVP K30)
(Reidel India chemicals, Mumbai, India), sodium starch
glycolate, talc (Nice chemicals, Cochin, India) and di-
rectly compressible lactose (S.D. fine chemicals Ltd,
Mumbai, India). All other chemicals used in the study
were of analytical grade.
2.2. Experimental Design
A Taguchi design [L16(45)] was implanted to study the
effect of formulation variables in the development of
timed release press-coated tablet. The Taguchi method
utilizes orthogonal arrays are essentially fractional facto-
rial experimental design to study the large number of
variables with a small number of experiments. Generally
a full factorial design would yield large experiments
with replication of centre points.
The levels of the 3 independent variables are as fol-
lows;
X1= Type of Hydrophillic polymer (HPMC, NaCMC,
HPC and HEC)
X2= Hydrophilic polymer/EC (1:1 to 4:1)
X3= Amount of magnesium stearate (0 to 10%)
The response variables tested include:
Y1 = Lag time (time required for 10% of drug release
in hour)
Y2 = Percent drug release at 8 hrs.
2.3. Preparation of Core Tablet
A direct compression method was adapted to prepare the
core tablet. As shown in Table 1, Theophylline anhy-
drous, lactose, PVP K30 and sodium starch glycolate
were mixed in a suitable stainless steel vessel in a tum-
bler mixer (Rimek, Karnavati Engineering Ltd. Ahmed-
abad, India) at 100 rpm for 30 min. thoroughly after pass-
ing through 80 mesh screen. Further, magnesium stearate
and talc were added to the above powder mixture and
blended for 10 min. Finally the resulting powder blend
was compressed by using a 10-station rotary tablet com-
pression machine (Rimek, Ahmedabad, India) fitted with
8mm standard concave punches. Preparation was per-
formed in 100 tablet batches and compression was con-
trolled to produce 4 ± 0.5kg/cm2 tablet crushing strength.
2.4. Preparation of Press-Coated Tablet
The formulations were prepared at random following
Taguchi design. Prior to compression all the ingredients
were passed through 80 mesh screen. The core tablets
were press-coated with an appropriate blend of polymers
with or with out magnesium stearate as given in Table 2.
Half the quantity of outer coating material was weighed
and transferred into the die; manually the core tablet was
placed carefully in the centre of the die. Then, the re-
maining half quantity of outer coating material was
added into the die and compressed by using 10-station
rotary tablet compression machine (Rimek, Ahmedabad,
India) fitted with 11 mm standard concave punches and
compression was controlled to produce 14 ± 0.5kg/cm2
tablet crushing strength.
2.5. In Vitro Dissolution Studies
The dissolution was performed by using USP dissolution
apparatus II paddle assembly (TDT-06T, Electrolab, In-
dia) at 37˚C + 1˚C using 750 ml of pH 1.2 buffer for the
first 2 hours and followed by 900 ml of pH 6.8 buffer till
the end of dissolution studies. The paddle rotational
speed was set to 100 rpm. Aliquots samples were with-
drawn at specified time intervals and the samples were
Table 1. Composition of core layer of press-coated tablet.
Ingredients Quantity
(mg/tablet)
Theophylline anhydrous 100
Sodium starch glycolate 10
Polyvinylpyrrolidone 5
Magnesium stearate 1
Talc 2
Lactose 32

C. Narendra et al. / Natural Science 2 (2010) 379-387
381
Table 2. Composition of coat layer of press-coated tablets
based on Taguchi design with observed responses.
Formula-
tion code
X1
Type
X2
Ratio
X3
(%)
Y1
(Hr)
Y2
(%)
F1 HPMC 1:1 0 5.3 ± 0.6 10.51 ± 2.01
F2 HPMC 2:1 10 7.5 ± 0.5 10.05 ± 3.16
F3 HPMC 3:1 0 3.4 ± 0.3 12.30 ± 2.37
F4 HPMC 4:1 10 7.1 ± 0.5 42.40 ± 1.15
F5 NaCMC 1:1 0 1.4 ± 1.1 100*
F6 NaCMC 2:1 10 3.1 ± 1.6 100*
F7 NaCMC 3:1 0 2.5 ± 0.9 100*
F8 NaCMC 4:1 10 4.2 ± 0.7 98.14 ± 3.34
F9 HPC 1:1 10 5.5 ± 0.5 100.81 ± 4.22
F10 HPC 2:1 0 2.3 ± 1.3 103.68 ± 3.14
F11 HPC 3:1 10 7.1 ± 0.5 98.87 ± 4.06
F12 HPC 4:1 0 2.8 ± 1.0 114.87 ± 4.13
F13 HEC 1:1 10 4.6 ± 0.3 14.13 ± 4.05
F14 HEC 2:1 0 2.5 ± 0.9 14.32 ± 3.55
F15 HEC 3:1 10 5.2 ± 0.6 11.98 ± 3.22
F16 HEC 4:1 0 2.6 ± 0.5 16.05 ± 3.37
*100% drug release was observed before 8 hrs of dissolution studies.
analyzed spectrophotometrically (UV-1601, Shimadzu,
Japan) at 271 nm and the amount of drug released was
determined from the calibration curve. The volume of
the sample withdrawn each time was replaced with the
same volume of the respective buffer solution. The stud-
ies were carried out in triplicate and mean values plotted
verses time with standard error of mean, indicating the
reproducibility of the results.
2.6. Statistical Analysis
The effect of formulation variables on the response
variables were statically evaluated by applying one-way
ANOVA at 0.05 level using a commercially available
software package Design-Expert® version 6.05 (Stat-
Ease, Inc.). The design was evaluated by using a suitable
model. The best fit model was selected based on the
several statistical parameters including multiple correla-
tion coefficient (R2), adjusted multiple correlation coef-
ficient (adjusted R2) and the predicted residual sum of
square (PRESS). For the model to be chosen as best fit,
the PRESS valve should be small relative to the other
models.
Linear model
Y= b0 + b1X1+ b2X2 + b3X3
Two factor interaction model
Y= b0 + b1X1+ b2X2 + b3X3+ b4X1X2+b5X1X3+b6X2X3
where Y is the response variable, b0 the constant and b1,
b2, b3,…,b5 is the regression coefficient. X1, X2 and X3
stand for the main effect; X1X2, X1X3 and X2X3 are the
interaction terms, show how response changes when two
factors are simultaneously changed.
3. RESULT AND DISCUSSION
3.1. Experimental Design
Taguchi method as design of experiment was chosen for
the organization of the experiments and analysis of the
results. Normally a full factorial design for such experi-
ment would yield 4 × 4 × 2 = 32 experiments. In the
present case, L16 orthogonal array, a mixed-level design
(2 factors at 4 levels and one factor at 2 levels) was con-
sidered and the size of experimentation was represented
by symbolic arrays i.e. 16 experiments [21]. The use of
more than two factors makes it possible to study some of
the eventual non-linear effects with interactions between
the factors. The statistical analysis to select the model
that best fits the data was obtained by analyzing the re-
sults of sequential model given in the Table 3. As seen
from the table, though the linear model was found to be
significant but the PRESS value for a two factor interac-
tion model (2FI) was found to be least hence, 2FI model
was considered to analyze the response lag time. For the
response percent drug release at 8 hrs, linear model was
found be significant with low PRESS value and the same
model was further navigated for ANOVA studies.
3.2. Effect of Type of Hydrophilic Polymers
Figures 1-4 show the release profile of press-coated
tablets in accordance to type of hydrophilic polymer. If
HPMC as type of hydrophilic polymer, increasing the
amount of HPMC in the coating layer, formulations F1,
F2 and F3 exhibited a minimal drug release at the end of
dissolution studies. Such a type of decrease in drug re-
lease may be due to increased amount of EC in the coat-
ing layer retarded the rate of hydration of HPMC which
Table 3. Comparison of sequential model.
Y
1 (hr) Y1 (%)
Statistical
Parameters Linear 2FI Quadratic Linear 2FI Quadratic
R2 0.8754 0.9940 0.9941 0.9773 0.9910 0.9953
Adjusted R2 0.8132 0.9704 0.9558 0.9660 0.9550 0.9648
PRESS 16.11724 9.2977 20.88 1907.033 7752.664 9088.802
p Valve 0.0003* 0.0522 0.9563 < 0.0001* 0.713 0.3079
* denotes significant p < 0.05.

C. Narendra et al. / Natural Science 2 (2010) 379-387
382
0.00
20.00
40.00
60.00
80.00
100.00
0.00 2.004.006.008.0010.0012.00
Time (hr)
Cumilative % drug released
F1
F2
F3
F4
Figure 1. Dissolution profiles of press-coated tablets contain-
ing HPMC as type of hydrophilic polymer.
0.00
20.00
40.00
60.00
80.00
100.00
120.00
0.00 2.00 4.006.008.0010.00
Time (hr)
Cumilative % drug released
F5
F6
F7
F8
Figure 2. Dissolution profiles of press-coated tablets contain-
ing NaCMC as type of hydrophilic polymer.
in turn hindered the drug release. In case of formulation
F4, the release from the tablet was more in a sustained
manner than a burst release which may be due to slower
hydration of HPMC and also this formulation contains
least amount of EC than the other formulations of
HPMC.
Similar but opposite result was observed in case of
NaCMC, that all the formulations show a relative, slow
initial drug release for first 2 hours then the release in-
creases quickly to 100% with in 8 hours of dissolution
studies. This behavior of increase in drug release may be
0.00
20.00
40.00
60.00
80.00
100.00
120.00
0.00 2.00 4.00 6.00 8.0010.00
Time (hr)
Cumilative % drug released
F9
F10
F11
F12
Figure 3. Dissolution profiles of press-coated tablets contain-
ing HPC as type of hydrophilic polymer.
0.00
10.00
20.00
30.00
40.00
50.00
0.00 2.00 4.006.00 8.0010.00
Time (hr)
Cumilative % drug released
F13
F14
F15
F16
Figure 4. Dissolution profiles of press-coated tablets contain-
ing HEC as type of hydrophilic polymer.
due to high solubility of NaCMC at pH 6.8 [22] also this
polymer undergoes a quick gel erosion rate and complete
disintegration of polymer matrix. In case of HPC as type
of hydrophilic polymer, the dissolution behavior was
characterized by sigmoid, S-shaped curve release profile
with a prolonged lag time and a complete drug release
from the core tablet was observed at the end of dissolu-
tion studies due to separation of coating layer into two
halves allowing the core tablet exposed to dissolution
medium (observation made during the dissolution stud-
ies). HEC as a type of hydrophilic polymer, the release

C. Narendra et al. / Natural Science 2 (2010) 379-387
383
at the end of dissolution studies were found to be less
than 18% which may be due to high viscosity of polymer,
decreased water uptake to form a gel matrix [23] and
presence of hydrophobic components such as EC and
magnesium stearate further prevented the hydration rate.
3.3. Effect of Hydrophilic/EC Ratio
EC, a cellulose ether derivative most widely used as wa-
ter insoluble polymer for coating of solid dosage forms.
Besides as controlled release barrier, they have also been
used as moisture barrier to improve stability of hydro-
lytically liable drugs [24]. The effect of hydrophilic/EC
ratio in presence and absence of magnesium stearate on
the release properties are summarized in Table 4. On
comparison of values, increasing the hydrophilic/EC
ratio, HPMC containing formulations exhibited a nega-
tive effect on lag time where as a positive effect was
observed in case of other hydrophilic polymers. HPMC
and HEC containing formulations showed no complete
drug release from the tablet even at the end of dissolu-
tion studies which is probably due to slow hydration rate
(because of hydrophobic components) and also the hy-
drogel layer therefore formed was strong enough and
could inhibit further water penetration into the inside of
core tablet [25,26].
In case of NaCMC and HPC, they did not show sig-
nificant difference in their release profile at the end of
dissolution studies except that NaCMC containing for-
mulations exhibited shorter lag time with complete drug
release with in 8 hours of dissolution studies where as in
case of HPC containing formulations exhibited longer
lag time with complete drug release at the end of disso-
lution studies. Such a type of release behavior may be
due to faster hydration followed by a combination of
disintegration and high erosion rate for the former where
as moderate swelling with low erosion rate for the later
[26,27].
3.4. Effect of Magnesium Stearte
The effect of magnesium stearate on the lag time and
percent drug release at 8 hrs can be visualized from the
Table 4. The formulations containing magnesium stear-
ate exhibited an improved lag time but no improvement
was observed in case of percent drug release at 8 hrs.
The beneficial effect of magnesium stearate on the lag
time is probably due to its hydrophobic nature prolongs
the lag time by significantly decreasing the water uptake
Figure 5. Main effect plot for type of hydrophilic
polymer (X1) on lag time (Y1) by keeping factors X2
and X3 at lower level.
and penetration through the coating layer [28].
3.5. Statistical Analysis
The model terms for Y1 (lag time) were found to be sig-
nificant with an F value of 42.10 (0.0052), high R2 value
of 0.9940 indicate the adequate fitting of two factor in-
teraction model. As shown in Table 5, factors X1, X3 and
interaction factors X1X2 and X1X3 were found to be sig-
nificant.
At lower level of factors X2 and X3, changing the type
of hydrophilic polymer from HPMC to HEC the lag time
decreases but at higher level of factors X2 and X3, the lag
time increased to a greater value if HPMC and HPC
were used as the type of hydrophilic polymer, where as
in case of NaCMC and HEC the effect was found to be
negative (Figures 5 & 6).
Changing the factor X3 from lower to higher level, a
significant positive effect on the lag time was observed
with irrespective of type of hydrophilic polymer and
hydrophilic /EC ratio.
The interaction effect between the factors X1X2 can be
studied with the help of Figures 7 & 8.
In presence or absence of magnesium stearate, if X2
was increased from lower to higher level and by
Table 4. Comparison of release parameters prepared from different types of hydrophilic polymers.
HPMC NaCMC HPC HEC
Response 1no MgSt 2MgSt 3no MgSt 4MgSt 5no MgSt 6MgSt 7no MgSt 8MgSt
Y1 (Hr) 4.35 7.3 1.95 3.65 2.55 6.3 2.55 4.9
Y2 (%) 11.405 26.229 100 99.07 109.275 99.84 15.185 13.055
Mean values from the formulations 1F1-F3, 2F2-F4, 3F5-F7, 4F6-F8, 5F10-F12, 6F9-F11, 7F14-F16, 8F13-F15.
Y1= Lag time
HPMCNaCMC HPC HEC
0.80
2.47
4.15
5.82
7.50
X1

C. Narendra et al. / Natural Science 2 (2010) 379-387
384
Table 5. Summary of ANOVA table for dependent variables from Taguchi design.
Source d.f. Sum square Mean square F value Probability
Y1 (Hr) R2 = 0.9940
Model 12 55.04 4.59 42.10 0.0052*
X1 3 19.29 6.43 59.01 0.0036*
X2 1 0.46 0.46 4.18 0.1334
X3 1 26.34 26.34 241.70 0.0006*
X1X2 3 3.30 1.10 10.10 0.0446*
X1X3 3 4.38 1.46 13.41 0.0304*
X2X3 1 0.60 0.60 5.51 0.1005
Y2 (%) R2 = 0.9773
Model 5 29611.65 5922.33 86.34 < 0.0001*
X1 3 29388.78 9796.26 142.82 < 0.0001*
X2 1 221.52 221.52 3.23 0.1025
X3 1 1.36 1.36 0.02 0.8910
d.f. denotes degree of freedom; * denotes significant p < 0.05.
Figure 6. Main effect plot for type of hydrophilic
polymer (X1) on lag time (Y1) by keeping factors X2
and X3 at higher level.
changing the type of hydrophilic polymer, only HPMC
containing formulations showed negative effect where as
other hydrophilic polymers showed positive effect on the
lag time.
The interaction effect between the factors X1X3 can be
studied with the help of Figures 9 & 10.
From this figures it may be concluded that presence of
magnesium stearate in the coating layer exhibited a posi-
tive effect on the lag time with irrespective levels of
factors X1 and X2.
A linear model for Y2 (percentage drug release at 8 hrs)
was found to be significant. In this case, only factor X1
was found to be significant (Table 5). As the factor X1
was increased from lower to higher level, NaCMC and
Figure 7. Interaction effect plot between type of hydro-
philic polymer (X1) and hydrophilic polymer/EC ratio
(X2) on lag time (Y1) at lower level of factor X3. (▪
Lower level; ∆ Higher level).
HPC containing formulations exhibited an increased
amount of drug release where as incase of HPMC and
HEC containing formulations exhibited very less amount
of drug release (Figures 11 & 12). This type of behavior
may be attributed due to low hydration rate of these
polymers in presence to EC and magnesium stearate and
if so hydrated they formed a dense layer which further
decreases the water diffusion into the core layer and de-
layed the release of drug from the dosage form [29].
4. OPTIMIZATION
To optimize the studied responses with different targets,
Y1= Lag time
X1
HPMC NaCMC HPC HEC
0.82
2.49
4.16
5.83
X2
X1
HPMC NaCMC HPC HEC
1.40
3.20
5.01
6.82
8.62
Y1= Lag time

C. Narendra et al. / Natural Science 2 (2010) 379-387
385
Figure 8. Interaction effect plot between
type of hydrophilic polymer (X1) and
hydrophilic polymer/EC ratio (X2) on lag
time (Y1) at higher level of factor X3. (▪
Lower level; ∆ Higher level).
Figure 9. Interaction effect plot between
type of hydrophilic polymer (X1) and
amount of magnesium stearate (X3) on
lag time (Y1) at lower level of factor X2.(▪
Lower level; ∆ Higher level).
Figure 10. Interaction effect plot between
type of hydrophilic polymer (X1) and
amount of magnesium stearate (X3) on lag
time (Y1) at higher level of factor X2 (▪
Lower level; ∆ Higher level).
Figure 11. Main effect plot for type of hydrophilic
polymer (X1) on % drug release at 8 hrs (Y2) by keep-
ing factors X2 and X3 at lower level.
a multi-criteria decision approach, like numerical opti-
mization technique by the desirability function was used
to generate the optimum settings for the formulation. [30,
31] The variables were optimized for the response Y1
and Y2 and the optimized formulation settings were ar-
rived by maximizing the percent drug release at 8 hrs and
lag time was kept at range between 6 to 7 hours. According
to the statistical prediction, the optimal values obtained
Figure 12. Main effect plot for type of hydrophilic polymer
(X1) on % drug release at 8 hrs (Y2) by keeping factors X2
and X3 at higher level.
was: HPC for type of hydrophilic polymer, hydrophilic
polymer/EC ratio ranged between 2.5: 1 to 4: 1 and
magnesium stearate also was ranged between 26-30 mg.
Since, the Taguchi design is used to screen the formula-
tion variables and to study their significant effect [32],
the results from optimization studies was found to be in
wider range and suggesting further studies to arrive to
the optimal settings.
Y2 = % drug release at 8 hrs
HPMC NaCMC HPC HEC
10.05
37.13
64.20
91.27
118.34
X1
X1
HPMC NaCMC HPC HEC
0.33
28.96
57.60
86.23
114.87
Y2 = % drug release at 8 hrs

C. Narendra et al. / Natural Science 2 (2010) 379-387
386
5. CONCLUSIONS
A Taguchi design was performed to screen the effect of
formulation variables on the response lag time and per-
cent drug release at 8 hrs in the development of timed-
release press-coated tablets by applying computer opti-
mization technique. Type of hydrophilic polymer was
found to be the major factor affecting studied responses
and also the results demonstrated that the hydrophobic
agent, magnesium stearate could significantly prolonged
the lag time. Among the type of different hydrophilic
polymers studied, HPC was found to be more suitable
and other hydrophilic polymers did not demonstrate
beneficial effect (with in the studied variable limits) in
the development of timed-release press-coated tablets.
Based on the results of optimization studies it was con-
cluded that further studies are required to obtain the op-
timal settings.
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