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ABSTRACT
This investigation describes the preparation and in vitro evaluation of gastroretentive floating tablet of
theophylline. Two hydrophilic cellulose derivatives, Methocel K100M and Methocel K15MCR were evaluated
for their gel forming and release controlling properties. Sodium bicarbonate and citric acid were incorporated as
gas generating agents. The effects of soluble components (sodium bicarbonate and citric acid), gel forming
agents and amount variation of theophylline on drug release profile and floating properties were investigated.
Tablets were prepared by direct compression technique. Formulations were evaluated for in vitro buoyancy and
drug release study was evaluated for eight hours using USP XXII paddle-type dissolution apparatus using 0.1N
HCl as dissolution medium. The release mechanisms were explored and explained with zero order, first order,
Higuchi and Korsmeyer equations. The release rate, extent and mechanisms were found to be governed by
polymer and floating agent content. The content of active ingredient was also a vital factor in controlling drug
release pattern. It was found that polymer content and amount of floating agent significantly affected the mean
dissolution time, percentage drug release after 8 hours, release rate constant and diffusion exponent.
Keywords: Gastroretentive dosage form, floating tablet, theophylline, absorption window, hydrophilic polymer.
Besides these ingredients each tablet contains 25 mg ludipress, 4 mg aerosil and 2 mg magnesium stearate.
log (Mt/M∞) = logk + nlogt (4) super case II transport, which means the drug release rate
does not change over time and the drug is released by
Where, M∞ is the amount of drug release after infinite zero-order mechanism. In this case, the drug release is
time; k is the release rate constant which considers dominated by the erosion and swelling of the polymer
structural and geometric characteristics of the tablet; and (Ritger and Peppas, 1987). Mean dissolution time (MDT)
n is the diffusional exponent; indicative of the mechanism was calculated from dissolution data using the following
of drug release. For a tablet having cylindrical shape n equation (Mockel and Lippold, 1993):
value below 0.45 indicate Fickian diffusion and n value
between 0.45 and 0.89 indicate anomalous transport, often n
MDT = ( )k −1 / n
termed as first-order release. If the n value reaches 0.89 or n +1
above, the release can be characterized by case II and
Table 2: Floating lag time and release parameters of folating tablets of theophylline
70.0
60.0
Time (sec)
50.0
40.0
30.0
20.0
10.0
0.0
0
2
F-1
F-2
F-3
F-4
F-5
F-6
F-7
F-8
F-9
F-1
F-1
F-1
Formulation
Fig. 1: In vitro floating lag time of gastroretentive floating tablets of Methocel K100M (F1~F-6) and K15MCR (F-
7~F-12).
Fig. 2: Pictorial presentation of in vitro floating behavior of a representative tablet of Methocel K100M.
(a)
100 100.0
80.0
80
% Release
% Release
60.0
60
40.0
40
20.0
20
0.0
0 0 2 4 6 8
Time (Hour)
0 2 4 6 8
Time (hour) F-7 F-8 F-9
F-10 F-11 F-12
F-1 F-2
60
upon the drug release was to some extent lost which is
demonstrated by the standard error bars parallel to Y-axis.
40
From figs. 3 and 4 it is clearly observed that increasing
amount of floating agent caused the increase of release
20
rate and extent which was particularly significant at the
0
initial stages of the dissolution study.
0 2 4 6 8
Time (Hour) Impact of Theophylline content on release profile
From the zero order release profile it was observed that
F-5 F-6 the total percent release of theophylline from those three
formulations which contained 75 mg of floating agent
Fig. 3: Zero order plot of release kinetics of Theophylline were decreased gradually due to the increase of amount of
showing the variation of drug release due to change of theophylline. The results resemble with the previous
amount of floating agent from various formulations of finding; the increase of amount of insoluble component
Methocel K100M. (increase of theophylline which in an insoluble drug)
caused the reduction in the percent release and reduction
(a) Theophylline 100mg, (b) Theophylline 200mg of zero order release rate (table 2). Similar pattern of
(c) Theophylline 300mg changes were also observed in case of F-2, F-4 and F-6.
Pak. J. Pharm. Sci., Vol.22, No.2, April 2009, pp.155-161 159
Theophylline loaded gastroretentive floating tablets based on hydrophilic polymers
12.00
10.00
Time (hours)
8.00
6.00
4.00
2.00
0.00
2
F-1
F-2
F-3
F-4
F-5
F-6
F-7
F-8
F-9
F-1
F-1
F-1
Formulations
Fig. 5: Mean Dissolution Time (MDT) of gastroretentive floating tablets of Methocel K100M (F1~F-6) and
K15MCR (F-7~F-12).