Mohammadi-Samani, S., Boostanian, A. (2010). The Effect of HLB on the Release Profile of Atenolol from Ethyl Cellulose-coated Tablets. Iranian Journal of Pharmaceutical Research, Volume 3(Number 3), 145-148.
S Mohammadi-Samani; A Boostanian. "The Effect of HLB on the Release Profile of Atenolol from Ethyl Cellulose-coated Tablets". Iranian Journal of Pharmaceutical Research, Volume 3, Number 3, 2010, 145-148.
Mohammadi-Samani, S., Boostanian, A. (2010). 'The Effect of HLB on the Release Profile of Atenolol from Ethyl Cellulose-coated Tablets', Iranian Journal of Pharmaceutical Research, Volume 3(Number 3), pp. 145-148.
Mohammadi-Samani, S., Boostanian, A. The Effect of HLB on the Release Profile of Atenolol from Ethyl Cellulose-coated Tablets. Iranian Journal of Pharmaceutical Research, 2010; Volume 3(Number 3): 145-148.
The Effect of HLB on the Release Profile of Atenolol from Ethyl Cellulose-coated Tablets
It is possible to alter the permeability of ethyl cellulose membrane with certain materials such as surfactants. In this study the effect of surfactant concentration and different HLB values on the release rate of atenolol from ethyl cellulose-coated tablets was evaluated. The results showed that when the concentration of surfactant increased, the rate of drug release also increased. The kinetics of atenolol release from these tablets also depended on surfactant concentration and their total HLB value. The data showed that there was an optimum HLB for an optimum rate of drug release. When the HLB value was increased to 9, the release rate increased and the kinetics of drug release approached a zero order model. But, further increase in HLB value up to 15 did not have any additional significant effect on the release rate of atenolol from these film-coated tablets.
It is possible to alter the
permeability of ethyl cellulose membrane with certain materials
such as surfactants. In this study the effect of surfactant
concentration and different HLB values on the release rate of
atenolol from ethyl cellulose-coated tablets was evaluated. The
results showed that when the concentration of surfactant
increased, the rate of drug release also increased. The
kinetics of atenolol release from these tablets also depended
on surfactant concentration and their total HLB value. The data
showed that there was an optimum HLB for an optimum rate of
drug release. When the HLB value was increased to 9, the
release rate increased and the kinetics of drug release
approached a zero order model. But, further increase in HLB
value up to 15 did not have any additional significant effect
on the release rate of atenolol from these film-coated tablets.
Over the last few decades, much attention
has been focused on designing oral controlled release dosage
forms. The polymeric film-coating technique has been used for
controlling the release rate of active ingredients from the
solid pharmaceutical dosage forms (1-5). Ethyl cellulose is
probably the most widely used water- insoluble polymer in
film-coating (6-10). Because of its good film forming
properties, much attention has been focused on the control of
the permeability of ethyl cellulose (2, 9, 11,). There are
several approaches to correct the permeability characteristics
of water insoluble polymers, which are used in film-coating. In
the coating process, surfactants could facilitate spreading of
the coating solution on the surface of the tablets (13). Small
amounts of non-ionic surfactants have also been used to wet and
homogenize the coating mixtures (14-16). Several researchers
previously showed that the release rate of active ingredients
from the film-coated tablets depended on the surfactants
concentration, which was added in the ethyl cellulose coating
solution (1, 13).
Atenolol, a model drug, is a polar
cardioselective b-blocker widely used alone or in combination to treat
essential hypertension. The administration of atenolol
conventional tablets, with doses of 100 mg/day may cause
fluctuations in plasma concentration, resulting in side effects
or a reduction in drug concentration at receptor sites.
Therefore, the objective of the present work was to apply a
film-coating technique for the controlled drug delivery of
atenolol (17).
In the present study the effects of
different HLB values of surfactants and their concentration
have been evaluated as release modulator moieties.
Experimental
Materials
Atenolol and ethanol (99%) were purchased
from Darou-Pakhsh (Iran), sodium phosphate dibasic, polyvinyl
pyrrolidone with molecular weight of 25000-30000, magnesium
stearate, dichloromethane and tween 80 were obtained from Merck
(Germany), span 60 was from Sigma and ethyl cellulose with a
viscosity grade of 1000 mPas was obtained from Hercules.
Methods
Formulation of core tablets
Atenolol core tablets were produced by
mixing atenolol, dicalcium phosphate and polyvinyl pyrolidone,
granulated with ethanol, and then passed through a No. 20
sieve. Sieved fraction was dried in an oven at 50°C for a
period of 1 h. The granules were mixed with magnesium stearate
for 2 min and then compressed into tablets on 12-mm concave
punches, using an Erweka single punch machine (Germany). The
weight of each tablet was within a range of 700±14 mg.
Each tablet theoretically contained 100 mg atenolol and the
compression pressure was adjusted so that the average hardness
of the tablets after compression was 5-6 kgf. Content
uniformity test was performed according to BP 1999 protocol for
atenolol tablets and the samples met the specified requirement
of the atenolol tablets mentioned in its monograph.
Preparation of polymeric solution with
different HLB values
Tween 80 (HLB 15) and span 60 (HLB 4.7)
were used to prepare different polymeric solutions with
different HLB values. The ratios of these surfactants in each
formulation have been presented in Table 1.
Coating of tablet cores
The tablets were coated using the pan
coating technique. A conventional 25-inch diameter Erweka pan
(model AR 401) was used. In each experiment 200 g core
materials were coated. Dichloromethane and ethanol with a ratio
of 50:50 were used as the polymer and surfactant solvents, and
the polymer concentration in coating formulation was kept
constant (2% w/w). The coating process was performed until the
thickness of the polymeric layers became 40±5 µm.
The coated tablets were dried first in the pan and finally at
room temperature for 24 h and then the film-coated tablets were
used to evaluate the release profiles.
The thickness of polymeric layer was
evaluated by means of a digital micrometer (Mitutoyo, Japan).
For this purpose, dried-coated tablets were moistened with
water for 1 h and then free film was prepared and after drying
the film, its diameter was measured and the mean value of three
samples calculated.
Dissolution Studies
The release rate of atenolol from coated
tablet was investigated using the USP dissolution apparatus No.
1 (Erweka tablet dissolution tester DT70, Germany). Distilled
water was used as the dissolution media. The stirring rate of
the media was kept at 100 rpm. Coated tablets were placed in
900 ml of dissolution media and the temperature was maintained
at 37±0.1°C. At appropriate time intervals, 5 ml
samples were taken and filtered through a 0.45 µm
Millipore filter. Then the samples were analyzed at 223 nm by
means of an UV- visible spectrophotometer (Cecil 9000, U.K.).
After each sampling, the same amount of the dissolution medium
was replaced. A dilution factor was calculated and the observed
release data corrected based on the calculated dilution factor.
The mean of 6 determinations was used to calculate the drug
release profile from the samples obtained from each
formulation.
Results and discussion
The release profiles of atenolol from
uncoated tablets and each group of coated tablets with ethyl
cellulose solution having different ratios of ethyl cellulose:
tween 80 are shown in figure 1. The results show that when the
ratio of polymer:surfactant decreases, the rate of atenolol
release increases. According to this figure (Fig. 1) and based
on the kinetic analysis data which presented in table 2 it
seems that when the polymer:surfactant ratio is 10:5 the
release profile is optimum for releasing at least 80 % of
atenolol during 10 h and in this ratio the release kinetics
approaches a zero order model and becomes more uniform (18).
The release profiles of atenolol from
tablets, which have been coated with polymeric solutions with
different HLB values, have been presented in figure 2.
According to this figure (Fig. 2) and based on table 3, it is
obvious that there is an optimum HLB value for a suitable
release of active ingredient. Based on figure 2 and table 3,
when the HLB value increased from 4.7 to 7 and then to 9, the
rate of atenolol release increased (P<0.01), but when the
HLB value was increased from 9 to 12 or 15, no significant
difference in the release rates was obtained (P<0.35). In
this regard the zero order release rate constant of each
formulation has been compared with the next formulation,
with a higher HLB value and the ANOVA test was performed
to compare the release rate constants. Based on the release
data, an HLB value of 9 is found to be the best value for
obtaining an optimum release rate (releasing at least 80% of
atenolol during 10 h and because of zero order release
profile).
Conclusion
Surfactants have a profound effect on the
release rate and profile of atenolol from ethyl
Cellulose-coated tablets. Using proper amounts of surfactant
and a suitable HLB value, the release rate and kinetic of drug
release could be controlled. In the lower HLB values the rate
of drug release is low, because these surfactants are more
lipophilic and have lower water solubility. But with higher HLB
values, hydrophilicity of surfactants was increased. Due to
increase in the ratio of tween 80 at higher HLB values, water
solubility and hydrophilicity of surfactant mixtures were
increased. An increase in water solubility of surfactant
mixtures could produce a microporous matrix within the tablet
coat for water diffusion and increases the rate of atenolol
dissolution and diffusion to the dissolution medium. According
to Narisawa et al.,(8). the release of drugs from ethyl
cellulose-coated tablets is independent on their
physicochemical characteristics and therefore, similar release
pattern may be obtained for other drugs (9).
Acknowledgement
This project was financially supported by
the Shiraz University of Medical Sciences (Grant No.77-555).
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