Journal of Advanced Pharmaceutical Sciences
2011 Vol-1 Issue 1
B. Agaiah Goud et. al
FORMULATION AND EVALUATION OF BIOADHESIVE
BUCCAL TABLETS OF SIMVASTATIN
B. AGAIAH GOUD* AND KUMARA SWAMY SAMANTHULA*
Department of Pharmaceutics, S.R.R. College of Pharmaceutical Sciences,
Valbhapur, Elkathurthy, Karimnagar - 505 476, Andhra Pradesh, India.
The objective of this study was to develop mucoadhesive buccal tablets of
Simvastatin using mucoadhesive polymers. Simvastatin has short biological halflife (3hr), high first-pass metabolism and poor oral bioavailability (5%), hence an
ideal candidate for buccal delivery system. The tablets were prepared by direct
compression technique using carbopol-934, sodium carboxy methyl cellulose (Na
CMC) and hydroxyl propyl methyl cellulose (HPMC) as mucoadhesive polymers.
For poorly water-soluble drugs that do not show pH-dependent solubility, an
approach to increase the dissolution rate is the addition of solubilizing agents or
surfactants to the dissolution media. Formulations were evaluated for mass
variation, hardness, friability, drug content, swelling studies, erosion studies, invivo residence time, in-vitro release studies in pH 7.0 phosphate buffer with 0.5%
SDS and ex-vivo permeation studies through porcine buccal mucosa. Formulation
FS5 and FH5 exhibited controlled drug release (8hr). Formulation FS5 selected as
optimized formulation based on physicochemical parameters and ex-vivo
permeation studies and follows zero order drug release. FTIR studies show no
evidence on interaction between drug, polymers and other excipients. The results
indicate that suitable bioadhesive buccal tablets for simvastatin with desired invivo residence time and controlled release could be prepared.
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Key words: Mucoadhesion, sodium carboxy methyl cellulose, hydroxyl propyl
methyl cellulose, simvastatin, swelling index, buccal drug delivery.
Introduction
Oral drug administration has been one of the most suitable and widely accepted by the
patients for the delivery of most therapeutically active drugs. But, due to some unsuitable
physiological conditions of the gastro-intestinal tract like relatively poor absorption, presence
of various digestive enzymes of the gastrointestinal tract and first pass metabolism by hepatic
enzymes, the administration of some drugs is affected1,2. In recent years, delivery of
therapeutic agents through various transmucosal routes has received significant attention
owing to the agents that are subjected to first-pass metabolism or are unstable within the
acidic environment of the gastrointestinal tract.3
Mucoadhesive formulations have been researched for delivery to the mucosa of oral
(buccal, sublingual and gingival), eyes, nose, rectum and vagina4. Among these systems, the
buccal mucosa offers many advantages like relatively large surface area of absorption, easy
accessibility, simple delivery devices, avoiding hepatic first pass metabolism gastrointestinal
degradation and feasibility of controlled drug delivery.5 Through this route it is possible to
realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the
first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the
second case involves drug absorption through the mucosal barrier to reach the systemic
circulation.
Recently much attention has been focused on the design and evaluation of buccal drug
delivery systems keeping in view their potential for future market. Therefore a buccal drug
delivery system needs to be developed and optimized i.e., a bioadhesive buccal drug delivery
system will have to be developed which adheres to the buccal mucosa in a safe way for a
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satisfactory period of time so as to release the drug to the maximum possible extent in an
effective way. 6
Simvastatin is HMG Co - A reductase inhibitors widely used in the treatment of
hyperlipidemias and cardiovascular diseases and it is known to have low oral bioavailability
(5%) due to an extensive high first-pass effect and its availability in less dose size i.e., in few
mg. Hence, it is suitable candidate for buccal drug delivery. The aim of the present study was
to design and develop bioadhesive buccal tablets of simvastatin that could be applied to the
buccal mucosa to release the drug unidirectionally in buccal cavity in order to decrease
gastric irritation and avoid first pass effect for improvement in bioavailability, to reduce the
dosing frequency and to improve patient compliance.
Materials and methods
Materials
Simvastatin was gift sample from Aurobindo Pharma Ltd, Hyderabad, India.
Carbopol 934P was obtained from S.D. Fine Chemicals, Mumbai. Sodium carboxy methyl
cellulose, hydroxyl propyl methylcellulose K4M was obtained from Loba chemicals,
Mumbai. Micro Crystalline Cellulose obtained from Laksmi chemicals, India. PEG 6000
obtained from India glycol Pvt Ltd., Mumbai, India. All other ingredients used in
formulations were of analytical grade.
Preparation of buccal tablets
Buccal tablets were prepared by a direct compression method, before going to direct
compression all the ingredients were screened through sieve no.100, except lubricant all the
ingredients were thoroughly blended in a glass mortar with pestle for 15 min. After sufficient
mixing lubricant was added and again mixed for additional 2-3 min. The mixture is
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compressed using 8 mm flat faced punch on 8 stages rotary tablet compress machine (Rimek
Minipress Karnavati Eng. Ltd, Ahmadabad, India). Formulation chart is given in table 1. All
tablets contained MCC as filler, magnesium stearate as lubricant, butylated hydroxyl anisole,
citric acid, ascorbic acid as anti oxidants and bioadhesive polymers with different mixing
ratios of carbopol 934P and CMC sodium and carbopol 934P and HPMC K4M.
Table 1: The tablets were prepared using carbopol 934, Sodium CMC and HPMC K4M
with different ratios
Formulation code
FS1
FS2
FS3
FS4
FS5 FH1 FH2 FH3 FH4 FH5
CP:SCMC/CP:HPMC
5:1
3:1
2:1
1.4:1
1:1
5:1
3:1
2:1
1.4:1
1:1
Simvastatin
10
10
10
10
10
10
10
10
10
10
Carbopol-934
50
45
40
35
30
50
45
40
35
30
Na CMC
10
15
20
25
30
-
-
-
-
-
HPMC K4M
-
-
-
-
-
10
15
20
25
30
MCC
47
47
47
47
47
47
47
47
47
47
Magnesium stearate
02
02
02
02
02
02
02
02
02
02
02
02
02
02
02
02
02
02
02
02
Citric acid
02
02
02
02
02
02
02
02
02
02
Ascorbic acid
02
02
02
02
02
02
02
02
02
02
Total weight(mg)
125
125
125
125
125
125
125
125
125
125
Ingredients (mg)
Butylated hydroxyl
anisole (BHA)
CP: Carbopol, Na CMC: Sodium carboxy methyl cellulose, HPMC: Hydroxy propyl methyl
cellulose, MCC: Micro crystalline cellulose
Drug content
Ten tablets were taken and powdered; powder equivalent to one tablet was weighed
accurately and allowed to dissolve in 10 ml ethanol and make up to 100 ml with distilled
water on a rotary shaker overnight. After filtration through whatmann filter paper and
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sufficient dilution with distilled water, samples were analyzed spectrophotometrically at 239
nm (Elico SL – 159, Hyderabad, India). This procedure was repeated thrice. Amount of drug
present was determined from the standard curve of simvastatin.
Swelling study
Three buccal tablets were weighed individually (W1) and placed separately in 2% agar
gel plates with the core facing the gel surface and incubated at 37 ± 1°C. After every 1 h time
interval until 8 h, the tablet was removed from the petri dish and excess surface water was
removed carefully with blotting paper. The swollen tablet was then reweighed (W2) and the
swelling index (SI) were calculated using the formula given in equation (Vishnu et. al.,
2007).
Swelling Index = [(W2-W1) ÷ W1] × 100
Where,
W1 = initial weight of the tablet
W2 = final weight of the tablet
Matrix erosion
After swelling study, the swollen tablets were dried at 60°c for 24 h in an oven and
kept in desiccator for 48 h and reweighed (W3). Matrix erosion was calculated using
following formula.7
% Matrix erosion = [(W1-W3) ÷ W3] × 100
Surface pH study
The surface pH of the buccal tablets was determined in order to investigate the
possibility of any side effects in-vivo. As the acidic or alkaline pH may cause irritation to the
buccal mucosa, the pH was maintained to neutral as closely as possible. A combined glass
electrode was used for this purpose. The tablet was allowed to swell by keeping it in contact
with 1 ml of distilled water (pH 6.5 ± 0.05) for 2 h at room temperature. The pH was
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measured by bringing the electrode in contact with the surface of the tablet and allowing it to
equilibrate for 1 min.8
In vitro drug release of buccal tablets
The drug release rate from buccal tablets was studied using the USP type II
dissolution test apparatus. The dissolution medium consisted of 500 mL of phosphate buffer
pH 7.0. The release was performed at 37oC ± 0.5oC, with a rotation speed of 50 rpm.6 The
backing layer of buccal tablet was attached to the glass slide with instant adhesive
(cyanoacrylate adhesive). The slide was placed in to the bottom of the dissolution vessel.
Samples (5 mL) were withdrawn at predetermined time intervals and replaced with fresh
medium. The samples were filtered through filter paper and analyzed by UV
spectrophotometer at 239 nm.
Ex vivo permeation of buccal tablets
Tissue isolation: Porcine buccal tissue from domestic pigs was obtained from a local
slaughter house and used within 2 hours of slaughter. The tissue was stored in Krebs buffer
pH 7.0 at 40 C after collection. The epithelium was separated from the underlying connective
tissue with a surgical technique and delipidized membrane was allowed to equilibrate for
approximately one hour in receptor buffer to regain lost elasticity.
Study protocol: Ex vivo permeation study of simvastatin buccal tablets through the porcine
buccal mucosa was performed using Franz-type diffusion cell. The freshly excised porcine
buccal mucosal membrane was clamped between donor and receiver chambers of the Franztype diffusion cell, facing the mucosal side towards the donor compartment. The receiver
chamber was filled with fresh pH 7.0 buffer solution and after the buccal membrane was
equilibrated for 30 min 9. The buccal tablet was placed in donor chamber and 1mL of buffer
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solution (pH 7.0) was added10 and the receptor compartment was maintained at 37±0.20C and
continuously stirred at 50 rpm throughout the study.
Aliquots (2mL) were collected at predetermined time intervals and filtered through a
filter paper, and the amount of drug permeated through the buccal mucosa was then
determined by measuring the absorbance at 239 nm using a UV spectrophotometer. The
medium of the same volume (2mL), which was prewarmed at 37°C, was then replaced into
the receiver chamber.11 The experiments were performed in triplicate (n = 3) and mean value
was used to calculate the flux (J) and permeability coefficient (P).
J = (dQ/dt)
A
P = (dQ/dt)
ΔCA
Where
J is Flux (mg.hrs-1cm-2);
P is permeability coefficient (cm/h);
dQ/dt is the slope obtained from the steady state portion of the curve;
ΔC, the concentration difference across the mucosa and A the area of diffusion (cm2).
Due to the low permeability of drug from the formulation, permeation enhancer (PEG
6000) was added into the optimized formulation to increase the permeability. The
enhancement ratio for flux was determined by dividing the cumulative amount permeated of
simvastatin in the presence of PEG 6000 (Qenh) by the amount of simvastatin alone (Q control).
Enhancement ratioflux=Qenh/Qcon
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Kinetic modeling of drug dissolution profiles
The dissolution data was fitted to Zero order, First order, Higuchi and Korsmeyer Peppas to ascertain the kinetic modeling of the drug release. The method was adopted for
deciding the most appropriate model.12, 13
Release kinetics:
Data of in vitro release was fit into different equations to explain the release kinetics
of simvastatin release from buccal tablets. The kinetic equations used were zero order and
first order equations.
a) Zero order release kinetics:
It defines a linear relationship between the fractions of drug released verses time
Q = kt
Where, Q is the fraction of drug released at time t
K is the zero order release rate constant
A plot of the fraction of drug released against time will be linear if the release obeys zero
order release kinetics.
b) First order release kinetics:
Wagner assuming that the exposed surface area of a formulation decreased
exponentially with time during dissolution process suggested that drug release from most
slow release formulation could be described adequately by apparent first order kinetics.
The equation used to describe first order release kinetics is
In (1-Q) = -kt
Where,
Q is the fraction of drug released at time t and
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K is the first order release rate constant.
Thus, a plot of the logarithm of the fraction of drug remained against time will be
linear if the release obeys first order release kinetics.
Models of drug release mechanisms:
The release data of buccal tablets was fitted into different mechanism models like
Higuchi, Korsemeyer – peppas and Hixson – crowel models to interpret the drug release
mechanism from tablets.
a) Higuchi (Diffusion) equation:
It defines a linear dependence of the active fraction released per unit of surface (Q) on
the square root of time.
Q = kt1/2
Where,
k is the release rate constant.
A plot of the fraction of drug released against square root of time will be linear if the
release obeys Higuchi equation. This equation describes drug release as a diffusion process
based on the Fick's law, square root time dependent.
b) Korsemeyer – peppas kinetics:
A plot of the fraction of the logarithm of % drug released against logarithm of time
will be linear if the release obeys Korsemeyer – peppas equation.
Log Q = log k + n log t
Where, k is the release rate constant.
c) Hixson – crowel (Erosion) model:
This equation defines the drug release based on formulation erosion alone.
Q = 1-(1-kt)3
Where Q is the fraction of drug released at time t
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K is the release rate constant
Thus a plot between (1-Q)1/3 against time will be linear if the release obeys erosion equation.
Determination of the ex vivo residence time
The ex vivo residence time was determined using a locally modified USP
disintegration apparatus.14 The disintegration medium was composed of 500 mL pH 7.0
phosphate buffer maintained at 37◦C. The porcine buccal tissue was glued to the surface of a
glass slab, vertically attached to the apparatus. The buccal tablet was hydrated from one
surface using 0.5 mL of phosphate buffer pH 7.0 and then the hydrated surface was brought
into contact with the mucosal membrane. The glass slab was vertically fixed to the apparatus
and allowed to run in such a way that the tablet was completely immersed in the buffer
solution at the lowest point and was out at the highest point. The time necessary for complete
erosion or detachment of the tablet from the mucosal surface was recorded. The experiments
were performed in triplicate (n=3).
Stability of buccal tablets
Stability studies of buccal tablets were performed for optimized formulation in normal
human saliva. The human saliva was collected from humans and filtered through filter paper.
Buccal tablets were placed in separate petri dishes containing 5 mL of human saliva and
placed in a temperature-controlled oven for 6 hr at 37°C ± 0.2°C. At regular time intervals (0,
2, 4, and 6 hr), the buccal tablets were examined for change in color, surface area and
integrity.15 The experiments were repeated in triplicate (n = 3).
FTIR studies to determine the drug excipients compatibility
Fourier Transform Infrared (FTIR) analysis was performed to interpret the
interactions of drug with polymers and other ingredients. The powder sample along with KBr
was used for FTIR studies. The IR spectrum of a) pure simvastatin, b) physical mixture
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containing drug, CP 934 and HPMC K4M c) physical mixture containing drug, CP 934 and
SCMC d) optimized formulation were taken, interpreted and compared with each other.
RESULTS AND DISCUSSION
Weight variation, Thickness, Hardness, Friability and Assay:
The values of weight variation, thickness, hardness, friability and assay of the twenty
tablets (Table 2) were found to be within the limits of conventional oral tablets stated in the
Indian Pharmacopoeia (IP, 1996). The average mass ranged from 122.8 to 128.1 mg, thick-ness of the tablets varied from 1.55 mm to 1.86 mm, hardness of the tablets was in the range
3.5 to 4 kg/cm2 the friability ranged from 0.22 to 0.51 and the drug content ranged from
95.76 in formulation FS1 to 99.16 in formulation FS5, 95.42 in formulation FH1 to 101.42 in
formulation FH5. The mass, thickness, hardness, friability and assay of all compressed tablets
were within the limits as per USP.
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Table 2: Weight variation, Thickness, Hardness, Friability and Assay (n=20)
Hardness Friability Drug Content
Weight variation
Thickness
(mg)
(mm)
(kg/cm2)
(%)
(%)
FS1
124.6±0.20
1.76±0.16
3.8±0.5
0.23
97.65
FS2
126.1±0.11
1.86±0.13
4.0±0.3
0.48
96.53
FS3
125.6±0.17
1.76±0.14
3.5±0.5
0.51
95.76
FS4
128.1±0.10
1.63±0.16
3.8±0.2
0.22
98.32
FS5
127.0±0.19
1.68±0.15
4.0±0.5
0.35
99.16
FH1
123.5±0.42
1.55±0.25
3.7±0.2
0.38
97.53
FH2
124.2±0.31
1.56±0.14
3.5±0.5
0.41
101.42
FH3
122.8±0.56
1.62±0.17
3.8±0.3
0.29
97.47
FH4
124.4±0.25
1.56±0.17
4.0±0.3
0.25
98.64
FH5
126.3±0.13
1.48±0.14
3.5±0.1
0.28
95.42
Formulation
Swelling and Matrix erosion studies:
The bioadhesion and drug release profile are dependent upon swelling behavior of the
tablets. Swelling index increased as the weight gain by the tablets increased proportionally
with the rate of hydration. In swelling study, it was found that the amount of carbopol plays
an important role in swelling of the matrix and leads to the drug diffusion. The fastest
hydration rate was obtained from FH1 (HPMC K4M) and FS1 (Na CMC) that hydrated
above 44 % within 6 hr. It was observed that swelling rate increased with an increase in
carbopol polymer content of the prepared tablets. The maximum swelling was seen in the
formulations FS1 and FH1.
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The mucoadhesive polymers used were hygroscopic and retain large amounts of water.
Tablets containing HPMC K4M as secondary polymers were found to exhibit least matrix
erosion. This is because the presence of water that balanced the weight loss due to erosion
and was more evident for this groups, as they showed higher hydration rates. The plots of
percentage swelling index and matrix erosion are shown in [Fig 1 & 2].
50
18
45
% Swelling
1hr
35
2hr
30
3hr
25
4hr
20
5hr
15
6hr
10
% Matrix erosion
16
40
14
12
10
Series1
8
6
4
2
5
0
0
FS1 FS2 FS3 FS4 FS5 FH1 FH2 FH3 FH4 FH5
FS1 FS2 FS3 FS4 FS5 FH1 FH2 FH3 FH4 FH5
Formulation code
Formulation code
Fig 1: Percentage swelling of developed buccal tablets
Fig 2: Matrix erosion of developed buccal tablets
Surface pH study
The surface pH of all formulations was within a range of 6.2 to 7.0, close to neutral
pH. These results reveal that all the formulations provide an acceptable pH in the range of
salivary pH (6.6 to 7.0). They did not produce any local irritation to the mucosal route. The
results of all the above mentioned tests are shown in table 3.
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Table 3: Surface pH values of formulations
Formulation code
Surface pH
FS1
6.4 ± 0.31
FS2
6.6 ± 0.25
FS3
7.0 ± 0.19
FS4
6.4 ± 0.23
FS5
6.5 ± 0.24
FH1
6.5 ± 0.19
FH2
6.3 ± 0.22
FH3
6.2 ± 0.30
FH4
6.6 ± 0.21
FH5
6.8 ± 0.22
In vitro drug release of buccal tablets
An ideal controlled release system should be able to release the drug immediately to
attain the therapeutic level at a faster rate and maintain this drug level for a prolonged period
of time.16 In vitro drug release studies revealed that the release of simvastatin from different
formulations varies with characteristics and composition of matrix forming polymers as
shown in graphs. The release rate of simvastatin increased with decreased carbopol 934 and
increasing concentration of Na CMC and HPMC K4 M in FS5 and FH5 respectively. The
most important factor affecting the rate of release from the buccal tablets is the drug: polymer
ratio. Carbopol 934P is more hydrophilic and has excellent mucoadhesive, gelling properties
and also helps in sustaining effect. An increase in carbopol polymer concentration causes an
increase in the viscosity of the gel as well as formation of a gel layer with a longer diffusion
path. Therefore decrease of carbopol content delays the drug release from tablet core.
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The results indicate that as the concentration of secondary polymer increases in the
respective series, Higuchi diffusion mechanism turns to zero-order release profiles.
Increasing the concentration of secondary polymer in the formulations showed a sustained
effect on simvastatin release. The rapidly hydrating polymer dominated in controlling the
release of simvastatin from the buccal tablets, as seen from the dissolution profiles and
moisture absorption data. Release rate slowed down when increasing the concentration of
carbopol 934 and release rate increased with Na CMC and HPMC K4M from 1:1 to 1:3 ratios
in FS and FH series. The maximum cumulative percent of drug release from formulation FS5
could be attributed to the presence of higher amount of Na CMC and lower amount of
carbopol which will ionize at pH environment of the dissolution medium. This is because as
the proportion of these polymers in the matrix increased, there was an increase in the amount
of water uptake and proportionally greater swelling leading to a thicker gel layer. The
comparison of cumulative percent drug release of all formulations was shown in Figure 3 and
4.
Fig 3: Comparison of dissolution profiles of FS1 to FS5
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Fig 4: Comparison of dissolution profiles of FH1 to FH5
Kinetics of drug release and mechanism:
To know the release mechanism and kinetics of simvastatin, the release data was
fitted into mathematical models and n, r2 values for zero order, First order, Higuchi and
Peppas models were represented in table 4.The peppas model is widely used, when the
release mechanism is not well known or more than one type of release could be involved.
The semi-empirical equation17 shown as equation:
Mt/M∞ = ktn
Where, Mt/M∞ is fraction of drug released at time ‘t’, k represents a constant, and n is the
diffusional exponent, which characterizes the type of release mechanism during the
dissolution process. For non-fickian release, the value of n falls between 0.5 and 1.0; while in
case of fickian diffusion, n = 0.5; for zero-order release (case II transport), n = 1; and for
super case II transport, n > 1
18
. The release exponent “n” values were less than 0.5, which
indicates that the drug release from all the batches followed fickian mechanism. The higher
R2 values for Zero order and Higuchi suggest that the drug release follows zero order kinetics
with diffusion mechanism.
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Table 4: In-vitro release kinetics of the formulation
Formulation
zero-order
First-order
Higuchi
R2
Korsmeyer
Peppas
n
FS1
0.967
0.613
0.972
0.329
FS2
0.940
0.552
0.991
0.369
FS3
0.958
0.564
0.983
0.344
FS4
0.953
0.549
0.989
0.379
FS5
0.990
0.647
0.962
0.487
FH1
0.957
0.589
0.972
0.276
FH2
0.969
0.616
0.977
0.341
FH3
0.973
0.618
0.969
0.330
FH4
0.971
0.609
0.970
0.337
FH5
0.952
0.550
0.990
0.384
Ex-vivo drug permeation:
Based on the in-vitro drug release, ex-vivo residence time, in-vivo residence time,
swelling and matrix erosions of all formulations, the FS5 was selected for ex-vivo drug
permeation studies. The oral mucosa of pigs resembles that of humans more closely than any
other animal in terms of structure and composition and therefore porcine buccal mucosa was
selected for drug permeation studies.
The results of drug permeation from buccal tablets through the porcine buccal mucosa
reveal that simvastatin was released from the formulation and permeated through the porcine
buccal membrane and could possibly permeate through the human buccal membrane. The
drug permeation was slow and steady (Fig 5) and 15.97±0.18% and 23.58±0.21% of
simvastatin could permeate through the buccal membrane with and without enhancer (PEG
6000) in 8 hours with a flux of 0.68 mg h -1cm-2 and 1.23 mg h -1cm-2 and permeability
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coefficient was 0.068 cm/ hr and 0.123 cm/ hr, respectively. The flux and permeation
coefficient was increased to 0.68 to 1.23 mg h -1cm-2 and 0.068 to 0.123 cm/ hr with inclusion
of permeation enhancer in the formulation.
Fig 5: Ex-vivo permeation of simvastatin
Determination of ex-vivo residence time
The ex-vivo residence time is one of the important physical parameter of buccal
mucoadhesive tablets. The ex-vivo mucoadhesive properties of the tablets were determined
using porcine buccal mucosa. Formulation FH1 to FH5 showed higher retention time when
compared to the formulation FS1 to FS5 as showed in table 5. As the concentration of
carbopol decreased with increasing secondary polymer, the retention time decreased. This
test reflects the adhesive capacity of polymers used in formulations. The results revealed that
Na CMC containing formulations showed better bioadhesion than the HPMC K4M.
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Table 5: Ex-vivo residence time of buccal tablets
Formulation
Ex-vivo retention time (hr)
FS1
6.33
FS2
6.16
FS3
5.75
FS4
5.33
FS5
5.25
FH1
6.50
FH2
6.33
FH3
6.25
FH4
6.16
FH5
5.75
Stability of buccal tablets
Stability study was conducted only for optimized formulation (FS5). There was no
change in the color and integrity of the tablets. The data obtained from the study presented in
table 6. Physical properties of the simvastatin buccal tablets such as thickness and diameter
slightly changed owing to swelling of the system in human saliva, buccal tablets maintained
their integrity in the human saliva throughout the study, confirming the sufficient strength of
the system.
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Table 6: Stability profile of optimized formulation in human saliva
Sampling
interval(hrs)
Change
in color
Change in
surface
area(cm2)
0
NO
NO
NO
2
NO
0.5
NO
4
NO
1.3
NO
6
NO
2.1
NO
8
NO
2.8
NO
Change in integrity
Characterization of drug in buccal tablets
FTIR spectroscopic analysis
FTIR has been used to assess the interaction between drug and polymers. The FTIR
spectra of all samples are shown in Figure 8. Important peaks detected in the spectrum of
drug, polymers and formulations are described as follows:
The spectrum of pure simvastatin presented characteristic peaks at 3433.06 cm-1
(alcoholic O-H stretching vibration), 2977.89 cm-1 (methyl and methylene C-H asymmetric
and symmetric stretching vibration), 1730.03 cm-1 (lactone C=O and ester C=O stretching),
1460.01, 1382.87 cm-1 (methyl and methylene C-H bending vibration), and 1145.64 and
850.55 cm-1 (lactone and ester C-O-C bending vibration), respectively.
IR analysis (fig 8) revealed that there was no strong chemical interaction occurred
between drug with polymers and other ingredients used in buccal tablets.
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Figure 8: IR spectrum of a) Simvastatin, b) Simvastatin, carbopol and HPMC K4M,
c) Simvastatin, carbopol and Na CMC and d) optimized formulation
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CONCLUSION
The prepared bioadhesive buccal tablets of Simvastatin can help bypass extensive
hepatic first-pass metabolism and improve bioavailability. The buccal tablets showed that
NaCMC containing formulations showed better bioadhesion than the HPMC K4M. The drug
release rate of formulations prepared with HPMC K4M (Max.60.67%) was retarded due to
the high viscosity of the polymer and formation of complex matrix network when compared
to the low viscosity polymers Na CMC (Max.78.77%). Similarly, in-vitro permeation studies
showed 23.58% drug release of the sustained dosage form. It can be concluded that
formulation FS5 could be used to release the drug unidirectional in buccal cavity without the
risk of mucosal irritation.
ACKNOWLEDGEMENTS
The authors wish to thanks Aurobindo Pharma Ltd, Hyderabad, India for providing
simvastatin as a gift sample and also to the management of S.R.R College of Pharmaceutical
science, Elkathurthy, Karimnagar for providing necessary facilities to carry out the research
work.
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For Correspondence:
B. Agaiah Goud,
Principal & Professor
Dept. of Pharmaceutics
SRR College Of Pharmaceutical Sciences,
Valbhapur, Elkaturthy Karimnagar.
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