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ISSN: 2454-5546
Pharma technology
Research Article
Corresponding Author
A.Gaythri
K.V.K College of Pharmacy,
Department of
Pharmaceutics,
JNTUH Hyderabad, India
E-mail:
pharmarxpro@gmail.com
ABSTRACT
In the present investigation, an attempt was made to design and
develop of Sustained Release Ambroxol Hydrochloride Matrix
Tablets using the combination HPMC k 4 100 and carbopol 940, in
order to improve efficacy, reduce the frequency of administration,
and better patient compliance. Ambroxol hydrochloride is a potent
mucolytic agent capable of inducing bronchial secretions used in the
treatment of respiratory disorders. The Sustained release matrix
tablets containing Ambroxol hydrochloride were developed using
different drug: polymer ratios. Sustained release matrix tablets were
prepared by wet granulation method. Granules were prepared and
evaluated for loose bulk density, tapped bulk density, compressibility
index and angle of repose, shows satisfactory results. The prepared
tablets were further evaluated for uniformity of weight, hardness,
friability, thickness, content uniformity, In-vitro dissolution, drugexcipients interactions. The FT-IR studies revealed that there was no
chemical interaction between drug and excipients. In-vitro release
studies were carried out using USP XXII type II (paddle method)
dissolution apparatus at 50 rpm by taking 900 ml of 0.1 N HCl (pH
1.2) as dissolution medium for first 2 hours and later replacing it
with 900 ml pH 6.8 phosphate buffer solution for rest of the time
period at 37 0.50C. The release data was fitted to various
mathematical models such as, Higuchi, Korsmeyer-Peppas, Firstorder, and Zero order to evaluate the kinetics and mechanism of the
drug release. Among all the formulations, F 3 shows 98.97 % better
controlled release at the end of 11 hr.
Keywords: Ambroxol Hydrochloride, Matrix tablet, Sustained
release, carbopol 940 , Wet Granulation
INTRODUCTION
Dosage forms are designed to deliver
optimum dose of drug to the site of action to
produce desired pharmacological action and
also
to
achieve
the
effective
drug
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ISSN: 2454-5546
Pharma technology
Research Article
use
in
chronic
respiratory
release
tablets
of
Ambroxol
Materials
HPMC
K4
100,
Polyvinyl
Lab
Fine
Chem
Industries,
from
hetero
labs
hyderabad.
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ISSN: 2454-5546
Pharma technology
Research Article
transferred to a 200mL volumetric flask and
METHODOLOGY
Construction of Standard
Ambroxol hydrochloride
Graph
of
Preparation
dihydrogen
potassium
mixed.
of
0.2
(M)
phosphate
dihydrogen
potassium
solution:
phosphate
was
different
concentrations
of
ambroxol
measured
8.5
mL
of
concentrated
for
twice-daily
SR
formulation
was
distilled water.
data33.
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ISSN: 2454-5546
Pharma technology
Research Article
= 155.88 mg.
k0 = DI x ke
Total dose required = DT = DL + DM
where
DI
is
the
initial
dose
(i.e.,
= 49.02+155.88
= 204.9 mg
205 mg
ke = 0.693 / t1/2
maleate = 4 h
Therefore
ke = 0.693 / 4
= 0.1732 mg/h.
Availability rate R = ke x DI
= 0.1732 x 75
mg
of
ambroxol
hydrochloride,
were
= 12.99mg/h.
where tmax = 2 h
Therefore DL = 75-(12.99x 2)
= 49.02 mg.
Maintenance dose = DM = R x H
release.
Therefore DM = 12.99x 12
4
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ISSN: 2454-5546
Pharma technology
Research Article
polyvinylpyrrolidone
(PVP-K30)
in
These
granules
were
blended
with
* qs = quantity sufficient
Formulations
In the formulations prepared, the release
retardants
included
was
hydroxypropylmethylcellulose
(HPMC
a) Angle of Repose
The angle of repose of granules was
determined by the funnel-method. The
accurately weighed granules were taken in a
funnel. The height of the funnel was
AMB
HPMC
CARBOPOL
CC
PVP-
PA
MS
Talc Total
HCL
K100M
940
(mg)
K30
(mg)
(mg)
(mg)
F1
75
37.5
74.5
10
Qs
205
F2
75
56.5
55.5
10
Qs
205
F3
75
75
37
10
Qs
205
F4
75
37.5
74.5
10
Qs
205
F5
75
56.5
55.5
10
Qs
205
F6
75
75
37
10
Qs
205
(mg)
(mg)
and
glidant.
1%
w/v
solution
of
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ISSN: 2454-5546
Pharma technology
Research Article
V0 = Initial volume
Vf = final volume
tan = h/r
c) Compressibility Index (Carrs Index)
where, h and r are the height and radius of
tapped
is.
respectively.
densities.
In
theory,
the
less
CI = (TD-BD) x 100/TD
Tapped Density
d) Hausners Ratio
It is the ratio of tapped density and bulk
density. Hausner found that this ratio was
related to interparticle friction and, as such,
could be used to predict powder flow
properties. Generally a value less than 1.25
indicates good flow properties, which is
equivalent to 20% of Carrs index
calculated
using
the
following
formulae.
6
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Pharma technology
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i) Thickness
Twenty tablets from the representative
sample were randomly taken and individual
standard
deviation
values
were
calculated.
ii) Hardness
acceptable.
weight
(WA)
was
calculated.
calculated.
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Pharma technology
Research Article
where
release
rate
is
concentration
vi)In-Vitro
Characteristics
Drug
Release
C = K0 t
(1)
t is the time.
(2)
sample
was
analyzed
by
UV-visible
(3)
(4)
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ISSN: 2454-5546
Pharma technology
Research Article
The following plots were made using the invitro drug release data
standard
of
graph
of
Ambroxol
Ambroxol
Peppas model.
Mt / M = Ktn
(5)
respectively, which suggests that it obeys
structural
rate constant
and
geometric
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ISSN: 2454-5546
Pharma technology
Research Article
index, and drug content (Table 19). Angle of
repose was less than 29 and Carrs index
values were less than 16 for the granules of
all the batches indicating good to fair
flowability and compressibility. Hausners
ratio was less than 1.19 for all the batches
indicating good flow properties.
Table 2: Physical
Precompression Blend
Properties
Formulati
ons
Angle of
repose
()
Bulk
Density
(g/mL)
Tapped
Density
(g/mL)
Carrs
Index
(%)
Hausne
rs
ratio
F1
26.56
0.422 0.506
16.6
0
1.19
15.9
0
1.18
14.2
8
1.16
12.1
1
1.13
13.7
0
1.15
13.6
1
1.15
1.2
F2
Absorbance
28.75
0.481 0.572
0.8
0.6
y = 0.0198x + 0.0493
F3
29.05
0.276 0.322
R2 = 0.9968
0.4
0.2
F4
26.97
0.341 0.388
0
0
10
20
30
40
50
60
Concentration (mcg/mL)
F5
27.34
0.510 0.591
of
F6
28.77
0.533 0.617
Characterization of Granules
The granules for matrix tablets were
characterized with respect to angle of
repose, bulk density, tapped density, Carrs
10
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ISSN: 2454-5546
Pharma technology
Research Article
of
HPMC.
Increase
in
F.
Code
Hardness
(kg/cm2)
Thickness
(mm)
Weight
variation
Friabil
ity %)
F1
3.220.17
v204.81.48
(mg)
0.36
F2
5.50
0.44
5.500.31
205.40.54
0.39
F3
6.280.40
3.220.80
204.60.41
0.13
F4
6.160.55
3.200.20
203.81.64
0.11
F5
5.250.57
3.080.66
205.61.14
0.54
F6
5.080.30
3.330.25
204.20.83
0.58
3.370.25
11
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Pharma technology
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Time
(hrs)
1
F1
F2
F3
F4
F5
F6
26.2
24.4
22.93
22.16
21.25
22.82
35.7
28.5
39.86
31.08
32.28
36.71
49.5
41.2
46.82
42.58
43.88
46.36
60.71
58.3
55.87
57.73
56.46
57.83
84.43
76.9
79.89
73.83
74.25
76.25
95.29
94.6
87.07
80.87
83.89
85.93
10
98.3
91.97
90.14
90.63
93.06
12
98.97
92.22
93.55
Zero order
First
order
Higuchi
r2
r2
r2
0.926
0.821
0.977
KorsmeyerPeppas
r2
0.981
r2 = Correlation coefficient;
n= Diffusional exponent.
N
0.59
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Pharma technology
Research Article
13
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CONCLUSION
release
that
polymers
could
be
successfully
medications.
In:
375.
3. Chien YW. Controlled and modulated-
release
tablets
containing
hydrophilic
HPMC
drug
4. Shanmugan
delivery
P,
systems.
In:
Bandameedi
Drug
doi:10.4172/2157-7609.1000194
Metab
Toxicol,
2015;
6:
194.
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and
14
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ISSN: 2454-5546
Pharma technology
8. Hixson AW, Crowell JH. Dependence of
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