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ISSN 2349-7750
ISSN: 2349-7750
PHARMACEUTICAL SCIENCES
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Research Article
Corresponding Author:
M. Naga Ganesh,
Department of Pharmaceutics,
Geethanjali College of Pharmacy,
Cheeryal, Hyderabad,Telagana,
India-501301.
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Please cite this article in press as M.Naga Ganesh and Y.Madhusudan Rao, Formulation and Evaluation of
Elementary Osmotic Pump Doxofylline, Indo Am. J. P. Sci, 2016; 3(8).
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INTRODUCTION:
Osmotic pumps are controlled drug delivery devices
worked on the principle of osmosis. Wide range of
osmotic devices are avaliable, out of them osmotic
pumps are unique, dynamic and widely employed in
clinical practice. Osmotic pumps shows many
advantages like they (i) are easy to formulate and
simple in operation, (ii) improve patient acceptence
by decresing frequency of dosing (iii) shows good in
vitro in vivo correlation. However wide variety of
oral osmotic systems have been reported in literature,
but most important osmotic drug delivery system is
Theeuwes elementary osmotic pump (EOP). Due to
of its simple structure and high efficiency, EOPs are
the most important osmotic devices and more than
540 patents have been devoted. Procardia XL and
Adalat
CR
(nifedipine),
Acutrium
(phenylpropanolamine), Minipress XL (prazocine)
and Volmax (salbutamol) are examples of EOPs
currently available in the market [1-3]. In this drug
delivery system, the osmotic core is surrounded by a
semipermeable membrane drilled with a drug
delivery orifice. Once this system comes in contact
with the gastrointestinal fluids, the osmotically driven
water enters the system through the semipermeable
membrane, dissolves the soluble agents, and exits
through the delivery orifice. Because these systems
use osmotic pressure for the controlled delivery of
the active compound(s), delivery rates are expected
to be independent of gastrointestinal condition [4].
The rate of drug release from osmotic pumps is
dependent on the total solubility and the osmotic
pressure of the core. The highly dihydrogenmonoxide
(H2O) - soluble drugs may create considerable
osmotic pressures and may release the active drug at
desirable rates.
Asthma and COPD (Chronic Obstructive Pulmonary
Disease) are the most common life threatening
pulmonary disease that requires constant monitoring.
Doxofylline, a methyl xanthine derivative that works
by inhibition of phosphodiesterase IV activities, has
recently drawn attention because of its better safety
profile and similar efficacy over the most widely
prescribed analogue, theophylline, indicated for
asthma and chronic obstructive pulmonary disease
due to decreased affinities towards adenosine A1 and
A2 receptors. Doxofylline is chemically designated
as 7-(1, 3 dioxolone-2-yl methyl) theophylline.
Presence of a dioxolane group in position C-7
differentiates it from theophylline. Doxofylline is an
anti-tussive and bronchodilator used for maintenance
therapy in patients suffering with asthma and chronic
obstructive pulmonary disease (COPD) and is
extensively metabolized in the liver by demethylation
and oxidation to an extent of 80-90% and 48%
plasma protein bound. Elimination half life (t) is
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400
120
145
25
5
5
700
400
125
140
25
5
5
700
400
130
135
25
5
5
700
400
135
130
25
5
5
700
400
140
125
25
5
5
400
120
400
125
400
130
400
135
400
140
145
25
5
5
140
25
5
5
135
25
5
5
130
25
5
5
125
25
5
5
700
700
700
700
700
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Cellulose acetate
(gm)
Ethyl
cellulose
(mg)
PEG-400 (gm)
DBP(gm)
HPMC(gm)
Acetone(ml)
IPA(ml)
0.6
2
0.3
90
0.6
90
0.3
90
0.6
90
90
-
700
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Table 5: Comparative In- vitro drug release data of formulations containing Manitol as osmogen (F1 to F5)
Cumulative % drug release*
F1 F2 F3 F4 F5
Time
(Hrs)
F1
F2
F3
F4
F5
0.00
0.00
0.00
0.00
0.00
0.60.173
0.830.115
0.460.208
0.530.230
1.160.251
2.960.152
4.730.642
3.360.450
3.660.450
5.060.556
11.360.152
11.160.251
10.20.400
11.030.351
12.730.503
16.010.300
17.030.251
15.930.251
15.360.305
19.860.305
22.030.251
22.80.600
21.330.351
21.90.458
26.330.472
38.090.500
29.630.493
26.660.750
27.830.404
31.930.251
34.130.404
36.00.655
340.360
350.300
40.020.558
38.930.416
41.630.750
40.330.351
41.090.264
47.960.378
45.060.305
47.00.721
44.660.709
49.250.503
55.030.650
10
52.160.667
55.430.832
51.630.702
55.060.251
62.030.321
12
59.860.378
60.040.818
57.040.360
61.930.321
70.760.602
14
67.460.832
67.010.700
64.040.321
70.80.400
78.560.288
16
72.560.611
76.230.450
71.160.971
76.090.458
83.860.493
20
82.081.153
82.960.611
76.660.776
81.730.589
89.040.360
24
87.030.458
91.050.700
82.630.665
90.030.793
96.060.360
First
Higuchis
Korsemeyer-
order plot
order plot
Plot
Peppas plot
R2
R2
R2
R2
F1
0.976
0.989
0.982
0.987
0.947
Non-Fickian release
F2
0.980
0.976
0.903
0.977
0.948
Non-Fickian release
F3
0.968
0.986
0.977
0.966
0.934
Non-Fickian release
F4
0.990
0.981
0.987
0.996
0.964
Non-Fickian release
F5
0.980
0.961
0.972
0.914
0.957
Non-Fickian release
F.Code
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Mechanism of drug
release
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Table 7: Effect of percentage increase in weight upon coating on in vitro drug release profile.
Percentage increase in weight upon coating
Time (hrs)
1.90 %
2.61 %
3.45 %
4.86 %
6.50 %
8.05 %
Cumulative %
release SD
Cumulative %
release
Cumulative %
release
Cumulative
% release
Cumulative %
release
Cumulative
% release
30.85
41.75
17.24
19.56
0.430.152
1.160.251
40.30
50.56
24.96
25.37
2.230.321
5.060.556
60.249
65.98
29.78
29.85
10.20.500
12.730.503
70.37
71.29
40.12
33.77
15.260.450
19.860.305
82.34
85.89
60.69
35.91
19.80.800
26.330.472
98.24
90.82
71.54
45.91
26.70.458
31.930.251
82.57
65.01
30.960.802
40.020.558
97.68
78.26
36.60.793
47.960.378
--
--
99.87
--
--
--
--
89.3
43.760.776
55.030.650
10
--
--
--
49.150.650
62.030.321
12
14
16
20
24
-------
------
------
98.56
------
55.731.002
62.010.755
67.040.400
75.30.500
83.030.404
70.760.602
78.560.288
83.860.493
89.040.360
96.060.360
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4.Theeuwes, F. Elementary osmotic pump. J. Pharm.
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5. Shukla D, Chakraborty S, Singh S, Mishra B.
Doxofylline: a promising methylxanthine derivative
for the treatment of asthma and chronic obstructive
pulmonary disease. Expert Opin Pharmacother 2009;
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6. Sameer sheaikh, Nirali Dave, Anil chandewar and
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Eur. J. Pharm. Biopharm., 2006; 68: 289-97.
8. Ramakrishna., N.; Mishra, B. Plastizer effects and
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