Solid dispersions

Pharmaceutical Seminar VI
on
FORMULATION AND EVALUATION OF
GASTRO RETENTIVE FLOATING TABLETS
CONTAINING CEFPODOXIME PROXETIL
SOLID DISPERSIONS
Anita Yadav
B.pharma, 7th
sem
10490003
Cct,Devinagar-13, Butwal
06-Mar-13 1Pharmaceutical seminar VI

INTRODUCTION
 Cefpodoxime Proxetil (CP) is the orally active
ester prodrug of third generation Cephalosporin.
 CP is used orally for the treatment of mild to
moderate respiratory tract infections,
uncomplicated gonorrhea and urinary tract
infections.
 One of the major problems with this drug,
according to the BCS system (class IV) it has
very poor aqueous solubility and poor
bioavailability after oral administration.

 Solid dispersion (SD) is one of the most successful
strategies to improve dissolution rate of poorly
aqueous soluble drugs.
 SDs can be defined as molecular mixtures of poorly
water soluble drugs in hydrophilic carriers.
 Solid dispersion technique has been extensively used
to increase the solubility of a poorly water-soluble
drug.
 The mechanism by which the solubility and the
dissolution rate of the drug are increased includes:
reduction of the particle size of drug.06-Mar-13 3Pharmaceutical seminar VI

 The gastroretentive drug delivery systems can be
retained in the stomach and help in continuously
releasing the drug.
 Various gastro retentive techniques were used,
including floating, swelling, high density, and
bioadhesivity have been explored to increase the
gastro retention of dosage forms.
 Floating systems are low density systems that have
sufficient buoyancy to float over the gastric contents
and remain in the stomach for a prolonged period of
time.

 The formulations were found to be stable with
insignificant change in the physical properties of
tablets and these exhibited satisfactory physico
chemical characteristics.
 The study revealed that, floating tablets using SDs of
CP with skimmed milk powder can enhance its
solubility and dissolution rate.
 The objective of the present work was to improve the
dissolution rate and bioavailability of CP by
formulating gastro retentive floating tablets using
solid dispersion method.
.

MATERIALS AND METHODS
 Materials:-
 Cefpodoxime Proxetil was procured as a
gift sample from Cadila Pharmaceuticals Pvt.
Ltd. (Ahmedabad, India).
 Skimmed milk powder was kindly provided by
Gujarat Co-operative Milk Marketing Federation
Anand (India). All other chemicals and reagents
were of analytical grade.

 Methods:-
 Preparation of Solid Dispersions (SDs) by
Solvent Evaporation Method:-
• Solid dispersions of CP were prepared by solvent
evaporation method using skimmed milk powder
as carrier in the different weight ratios of 1:1, 1:2,
1:3 and 1:4 of drug: carrier polymer.
• Accurately weighed quantities of carrier (skimmed
milk powder) were added to the solutions of CP in
ethanol.

• The solutions were stirred at room temperature
and the solvents were allowed to evaporate.
Solid dispersions thus formed, were then dried
in vacuum oven for 24 hrs at room temperature,
pulverized and sieved through sieve no. 60.
• After the preparation of solid dispersions, the
powdered samples were stored in a closed
container away from light and humidity until use.

 Preparation of Physical Mixtures (PM):-
• Physical mixtures were prepared by mixing the
appropriate amounts of the drug and carrier
(skimmed milk) in the different weight ratios of
1:1, 1:2, 1:3 and 1:4 in mortar.
• The resulting mixtures were sieved through sieve
no. 80, collected and stored in closed container
away from light and humidity until use.

 Determination of Saturation Solubility:-
• Saturation solubility was determined by using shake
flask method.
• Excess quantities of pure CP, prepared SDs and PMs
were added in 25 ml distilled water in conical flasks
which were then put in orbital shaker at 37°C and at
100rpm for 72 hrs.
• Absorbance of resulting solution was measured on
UV/Visible Spectrophotometer.

 Determination of pH Dependent Solubility:-
• Shake flask method same as that for saturation
solubility was used with 0.1N HCl and
phosphate buffer saline (pH 7.4) as solvents.
 Percent Drug Content:-
• 10 tablets were weighed and powdered. An
amount of the powder equivalent to 8mg of CP
was dissolved in 100ml of 0.1N HCl, filtered,
diluted suitably and analyzed for drug content at
263nm using UV/Visible spectrophotometer.

 In Vitro Dissolution Studies
• In vitro dissolution studies of prepared SDs were carried out
using USP type 2 test apparatus . In all experiments, 5 ml of
dissolution sample was withdrawn at 5 min interval, filtered
using a 0.45-mm whatman filter, and replaced with an equal
volume of fresh medium to maintain a constant total volume.
Samples were analysed on UV/Visible spectrophotometer at
263nm.
 Formulations of Floating Tablets
• Each floating tablets containing SDs of CP and carrier
complex were prepared by a conventional wet granulation
method. The composition of various formulations is given in
Table 1.

Table : Composition of different floating tablet formulations of
SDs of CP06-Mar-13 13Pharmaceutical seminar VI

 Evaluation of Granules Properties:-
• Angle of Repose:-The angle of repose of was
determined by the funnel method and was
calculated as:
θ= tan-1(h/r)
• Bulk Density :-Both bulk density (BD) and tapped
bulk density (TBD) were determined by the
following formula
BD = Weight of the Powder/Volume of the
packing.
TBD = Weight of the powder /Tapped volume of
the packing.

• Compressibility Index/ Carr’s Index:-The
percentage compressibility of the bulk drug was
determined by using the following formula:-
Compressibility Index = Tap density – Bulk
density/Tap density x 100
 Evaluation of Floating Tablets:-
• In vitro Buoyancy determination studies:-In vitro
buoyancy studies were performed in a 100ml beaker
containing simulated gastric fluid, pH 1.2 as per USP.
The time taken for the tablet to rise to the surface and
float was taken as floating lag time (FLT). The duration
of time the dosage form constantly remained on the
surface of medium was determined as the total floating
time (TFT).

 Others evaluating parameters of CP tablets:-
• Thickness and diameter
• Weight variation
• Friability Test
• Hardness Test
• Percent Drug Count
• Determination of Percent swelling interest
• In-vitro Drug Release Studies
• Dissolution Studies Using USP Type II Apparatus
with Wire Sinker
• Stability Studies

RESULTS AND DISCUSSIONS
 The prepared SDs and PMs of CP were evaluated
for
• saturation solubility,
• pH dependent solubility,
• percent drug content, and in-vitro dissolution
studies.
 All PMs showed higher saturation solubility as
compared with pure CP.

Table 1: Saturation Solubility and pH Dependent solubility Studies of Pure
CP, SDs and PMs

Table 2: Percentage Drug Content of PMs and SDs

 The in vitro dissolution study of the pure CP,
SD4 and PM4 using skimmed milk powder as
carrier showed improved dissolution of CP
over that of pure CP.
 SD4 showed the fastest dissolution (92.35%)
than PM4 and pure.

Fig. 3: Percent Cumulative Drug Release by USP 2 and USP 2 Wire
Helix Apparatus

 Among these formulations, the in vitro Buoyancy
was increased in the following order: F4> F1 > F6 >
F3> F5> F2.
 The formulation showed a constant rate of release
in a sustained manner similar to zero order kinetics
with good buoyancy property.
 From the data, there was no significant change in
the percent drug content and other physical
parameters.

Table 4: Pre Compression Parameters of Granules
Table 5: In vitro Buoyancy determination

Table 6: General Characteristic of Floating Tablets

Table7: % Swelling Index (Percentage Water Uptake) of Floating Tablets

Fig. 3: Percent Cumulative Drug Release by USP 2 and USP 2 Wire Helix
Apparatus06-Mar-13 26Pharmaceutical seminar VI

Table 8: Stabilities studies of Floating Tablets

CONCLUSION:-
 According to the results obtained from the
experimental work, the SD 4 showed better
dissolution when compared with the pure CP.
 The study revealed that, floating tablets using SDs
of CP with skimmed milk powder can enhance its
solubility and dissolution
06-Mar-13
28
Pharmaceutical seminar VI

REFERENCE
 Sharma Neha, Jain Nidhi, CK Sudhakar, Jain Sanjay
(2012) Formulation and Evaluation of Gastro
Retentive Floating Tablets Containing Cefpodoxime
Proxetil Solid Dispersions. Int J Curr Pharm Res
4(4), 82-87

Solid dispersions

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