DEVELOPMENT AND EVALUATION OF FLOATING TABLETS OF CIPROFLOXACIN HCL - DISCUSSION
DISCUSSION
An attempt was made to formulate and
evaluate floating drug delivery system containing ciprofloxacin HCL as a model
drug, Ciprofloxacin HCl belong to fluoroquinoline
derivative which is widely used in the long term therapy for treatment of wide
range infection including anthrax, biliary tract infection, bone and joint
infection, gastrointestinal including traveler’s diarrhea and Campylobacter
enteritis and Shiegella. Hence
the floating form was developed.
Floating drug delivery system have a
bulk density less than gastric fluids and thus it remains buoyant in the
stomach without affecting gastric emptying rate for a prolonged period of time.
While the system is floating on the gastric contents, the drug is released
slowly at the desired rate from the system. After release of drug, the residual
system is emptied from stomach. This results in an increased gastric residence
time and a better control of the fluctuation in plasma drug concentration.
Single unit formulations (floating tablet) are associated with problems such as
sticking together or being obstructed in the gastrointestinal tract, which may
have a potential danger of producing irritation. On the other hand a floating
system made of multiple unit forms (floating tablets) has relative merits
compared to a single unit preparation. Floating tablets provide a constant and
prolonged therapeutic effect which will reduce dosing frequency.
The aim of present study was to
develop floating tablets of ciprofloxacin HCL by wet granulation technique by
using sodium alginate, HPMC K 4M, and carbopol
934 P as a polymer.
Preformulation Method
Calibration curve
In pre formulation studies it was found that,
the estimation of ciprofloxacin HCL by spectrophotometric method at 271 nm had
good reproducibility ( as shown in table 4).
Bulk Density
The bulk density of the Formulation
F1 to F4 ranges from 0.674±0.01gm/cm3
to 0.756±0.03gm/cm3, (containing HPMC K4M), formulation F5 to F8
ranges from 0.735±0.01 gm/cm3 to 0.812±0.04gm/cm3,
(containing Carbopol 934 P), formulation F9 to F12 ranges from 0.817±0.03gm/cm3
to 0.805±0.001gm/cm3 respectively (as shown in table no.5).
Tapped
Density
The
tapped density of the formulation F1 to F4 varied from 0.750 to 0.701,
formulation F5 to F8 varied from 0.732 to
0.889, formulation F9 to F12 varied from 0.981 to 0.974 respectively (as shown in table no.5).
Hausners
Ratio
The
hausners ratio of the entire formulation F1 to F12 were in the range of 1.11±0.09 to 1.14±0.02
(as shown in Table no.5)
Carr’s
Index
The carr’s index of
entire formulation F1 to F12 were in
range of 12.19±0.09 to 13.44±1.6 (as shown in table no.5) The Carr’s compressibility
index values showed up to 15% result in good to excellent flow properties.
Angle of repose (θ):
The
data obtained from angle of repose for formulations F1 to F12 were found to be
in the range of 15.23°q to 23.34°q. The angle of repose
less than 30°, which reveals good flow property.
Post formulation methods
Thickness
The thickness of
entire formulation F1 to F12 were in the range of 2.66 to 3.8.
Average weight
The average
weight of entire formulation F1 to F12 were in the range of 500.9 to 502.15.
Hardness
The hardness of
entire formulation F1 to F12 were in the range of 4.3±0.5 to 5.6±0.4.
Friability
The friability of
entire formulation F1 to F12 were in the range of 0.38 to 0.63.
In vitro Buoyancy Study
In
vitro floating studies were performed by placing tablet in beaker containing
0.1N HCl, maintained at temperature of 37±0.50C. The floating lag
time and floating time was noted visually. The results are given in table 13.
in the initial floating tablets of Ciprofloxacin HCl, formulation containing
drug and different polymers HPMC K4, carbopol 934 P and sodium alginate with
gas generating agents sodium bicarbonate (F1 to F12) the floating lag time was
found to be in between 67 seconds to 120 seconds and remained under floating
conditions for 24 hours.
Formulations
containing gas generating agent sodium bicarbonate at varying concentrations has
shown a floating lag time of 67 seconds to 120 seconds remained floating for 24
hours. The floating lag time was found to be more in the formulations which
contains less gas generating agent (sodium bicarbonate) in the which may be due
to delayed swelling of the polymer. It was observed that increasing the
concentration of sodium bicarbonate, there was a reduction in the floating lag
time, where the dissolution medium was imbibed into the matrix, the interaction
of acidic fluid with sodium bicarbonate resulted in the formulation F4
containing of 67 seconds for 24 hours.
In vitro drug release
In vitro drug release studies of
Ciprofloxacin HCL from floating tablets
were performed in pH 1.2 for 24 hrs using USP Type I dissolution test
apparatus. It was found that in vitro drug release of formulation F1 to F4 were
in the range of 72.02 to 94.07. Formulation F5 to F8 were in the
range of 87.92 to 91.03. Formulation F9 to F12 were in the range of 85.78 to 87.21
and formulation Among all formulations F4 was found to be the best
formulation as it release ciprofloxacin HCL 94.07%
in a sustained manner with constant fashion over extended period of time (for
24 hr).
It
was observed that the concentration of sodium bi-carbonate increased, lag time
decreased and percent of drug release of ciprofloxacin HCL increases.
The
release rates obtained were subjected for Kinetic treatment to know the order
of release. The ‘r’ values for zero order kinetics of formulation F1 to F12 are
0.9993, 0.9998, 0.9983, 0.9964, 0.9974, 0.9984, 0.9992, 0.9975, 0.9993, 0.9998,
0.9992 and 0.9996 respectively. The ‘r’ values indicates that drug release of all
formulation F 1 to F 12 follows zero order kinetics.
To
ascertain the drug release mechanism, the in-vitro data were also subjected to
Higuchi diffusion. The ‘r’ values of Higuchi diffusion was in the range of
0.923 to 0.976 of all formulation F1 to F12. It suggests
that the Higuchi diffusion plots of all the formulations were fairly linear
because ‘r’ values near about 1 in all the cases. So it confirms the drug
release by Higuchi diffusion mechanism.
The
release mechanisms of ciprofloxacin HCL
floating tablets also evaluated
on the basis of Peppas model. The n value of all formulations F1 to F12 are in
the range of 0.975 to 0.993 which is in the range of 0.5< n >1.0, which
indicate that tne mechanism of release of ciprofloxacin HCL floating tablets
are anomalous (non-Fickian) transport.
Infrared spectroscopy (FTIR )
The
prepared floating tablets were characterized by FTIR spectroscopy to find out
any chemical interaction between ciprofloxacin HCL and polymers used.
a
characteristic IR spectra of Ciprofloxacin HCL showed at 1699cm-1 for
C = O, for C-O str, 886cm-1
for O-H str, 2682cm-1 for C-O str, 886cm-1 for
N-H, 3739cm-1 for C-N bend, 1307cm-1 for C=C, 1490cm-1.
All these prominent peaks of drug is observed in formulation F4. Thus,
indicating the compatibility of drug with polymers and excipient used. Here,
the FT-IR Spectrum of ciprofloxacin HCL and “F4” are matching with each other.
So there is no interaction take place in optimized formulation as shown in
table 21.
The individual spectra
of drug ciprofloxacin hcl,
polymers sodium alginate, carbopol 934 P, HPMC K 4M, and excipient sodium
bi-carbonate as shown in figure. 33, 29, 34 and 31 respectively.
Stability Study:
The promising formulations were subjected to
short term stability study by storing the formulations at 25°C with relative
humidity 60 % and 40°C with relative humidity 75% showed the maximum stability.
The values of drug content and in vitro drug release were close to initial data
with only slight variations. Accelerated stability studies for 3 month revealed
that the formulations were stable upto 400C and 75% RH. It should be
stored in a cool, dry place. Stability study are shown in table 28.
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