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Formulation Development and Evaluation of the Dispersible Tablet of

Cefpodoxime Proxetil

Article · January 2012

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 International Journal of Pharmacy Research and Technology
2012, Volume 3, Issue 1, 06-10
ISSN 2250 – 0944 (Online)
ISSN 2250 – 1150 (Print)
Research Article
Formulation Development and Evaluation of the Dispersible Tablet of Cefpodoxime Proxetil

Bhatt Chintan*1, Yadav Kailash1, Tarachand Kumawat1, Shah Hardik1, Bhatt Dipak2,
Shah Chainesh3, Ramani Vinod4
1
Regional College of Pharmacy, Jaipur, Rajasthan.
2
Cadila Pharmaceutical LTD, Dholka, Gujarat.
3
Dept. of Pharmaceutics, R.H. Patel College of Pharmacy, Dahemi, Anand, Gujarat
4
Dept. of Pharmaceutics, C.K.Pithawala institute of Pharmaceutical Science and Research, Surat.
* Corresponding Author: Email: cbhatt215@gmail.com
Received: 20/12/2012, Revised: 05/01/2013 Accepted: 18/01/2013
ABSTRACT
In present research work, dispersible tablets of cefpodoxime proxetil were formulated using direct compression
technique using various granulation techniques and different disintegrating agents by various Pharmaceutical Exicipients.
Cefpodoxime proxetil is an advanced-generation, broad-spectrum cephalosporin antibiotic approved for the treatment of
acute bacterial exacerbation of chronic bronchitis (AECB), group-A beta haemolytic streptococcal pharyngotonsillitis, and
uncomplicated skin/skin structure infections in adult and adolescent patients. Cefpodoxime proxetil has slightly bitter taste,
poor flow propertyand poor water solubility. In this research work, initially the poor flow property was improved by
comparing various granulation techniques via Trial-1 wet granulation, Dry granulation Trial-2 Lactose, Micro crystalline
cellulose powder (MCCP), Carboxymethylcellulose (CMC) Calcium, Sodium lauryl Sulphate (SLS), and Croscarmellose
Sodium (CCS) and Polyvinylpyrrolidone (PVP) K30 and Trial-3 by Dry granulation MCCP, Maize starch and PVP K30.
The optimized formulation i.e. Trial-3MCCP, Maize starch, PVP K30 was incorporated with various Disintegrnat like SSG,
CCS and Crospovidone which is encoded as Trial-3A, Trial-3B and Trial-3C respectively. The prepared tablets were
evaluated by various post-compession parameters. Among 3 Batches Trial-3C using Crospovidone was found optimized
since it had expressed Disintegrating Timeof 20 sec and 99.98 ± 0.023 % CDR within 55min and furthermore also found
better when compared with other marketed ODT of Cefpodoxime proxetil.
Key words: Dispersible tablet, Pharmaceutical exicipients, Disintegrants, Disintegrating Time.

INTRODUCTION for geriatric or pediatric patients or for those who are

Tablets are solid preparations each containing single
dose of one or more active substances andusually obtained
by compressing uniform volumes of particles. Tablets are
intended for oral administration. Some are swallowed
whole,after being chewed, some are dissolved or dispersed
in water before being administered and some areretained in
the mouth where the active substance is liberated [1].Tablets
are the most widely used dosage form because of its
convenience in terms of self administration, compactness
and ease in manufacturing. But pediatric and geriatric
patients may encounter inconvenience in swallowing it. To
overcome this problem, in recent year’s increasing attention
has been focused in formulating fast dissolving and
dispersible tablets that are intended to dissolve or
disintegrate rapidly in the mouth. Tablet disintegration has
been considered as the rate limiting step in faster drug
release.[2]
Recent advances in Novel Drug Delivery System
(NDDS) aims to enhance safety and efficacy of drug
molecule by formulating a convenient dosage form for
administration and to achieve better patient compliance.
Tablets are the most widely utilized oral dose format. A
novel tablet concept which offers ease of oral
administration and increased patient compliance is the fast
dissolving / disintegrating tablet (FDDT)[3]. Dispersible
tablets are uncoated tablets intended to be dispensed in
water before administration giving a homogenous
dispersion. The tablets produced must have the ability to
form adequate dispersion which is uniform and stable when
placed in water. The chief advantage is quicker absorption
and onset of clinical effects. They are generally prepared
having difficulty in swallowing tablets. They comprise of
totally water soluble excipients and components.
Dispersible tablets disintegrate either rapidly in water, to
form a stabilized suspension, so, it’s preferred for paediatric
patients who cannot swallow a solid dosage form and the
API is unstable if formulated in liquid formulation, also
helpful for patients having prolonged illness who are prone
tonauseatic sensations if they have to swallow a tablet. The
added advantage of this formulation is faster onset of action
as compared to standard compressed tablet.[4] The
properties of the water dispersible tablet, such as porosity,
hardness, disintegration time and increase in viscosity after
dispersion are necessary to investigate during
manufacturing which decides the product performance.
Dispersible tablets as defined in Ph. Eur. are uncoated or
film coated tablets intended to be dispersed in water before
administration giving a homogeneous dispersion. Typically
a dispersible tablet is dispersed in about 5-15 ml of water
and the resulting dispersion is administered to the patient.[5]
Cefpodoxime proxetil is an advanced-generation, broad-
spectrum cephalosporin antibiotic approved for the
treatment of acute bacterial exacerbation of chronic
bronchitis (AECB), group-A betahaemolytic streptococcal
pharyngotonsillitis, and uncomplicated skin/skin structure
infections in adult and adolescent patients. Cefpodoxime
proxetil has slightly bitter taste, poor flow property and
poor water solubility. So in case of acute bacterial
exacerbation of chronic bronchitis (AECB) group-A beta-
haemolytic streptococcal pharyngo tonsillitis, and
uncomplicated skin/skin structure infections it require
immediate release of drug from the dosage form, which

6 | IJPRT | January – March

 Bhatt et al / International Journal of Pharmacy Research & Technology 2013 3(1) 06-10

make Cefpodoxime proxetil suitable candidate for Hausner’s ratio

dispersible tablets.[6]The purpose of the study to formulate Hausner’s ratio is an indirect index of ease of powder
Dispersible tablet of Cefpodoxime proxetil is to provide flow. It is calculated by the following formula.Hausner’s
fast release of drug, enhanced dissolution and solubility of ratio value is less than 1.5 indicates good flow and greater
drug, rapid onset of action may improved bioavaibility and than 1.5 indicates poor flow property.
improve dispersion of the drug in water by compression Tapped density
technique using various granulation techniques and Hausner ratio =
Bulk density
different disintegrating agents by various Pharmaceutical
Exicipients and also not compared with the marketed Angle of repose
formulations which have not been done yet. The angle of repose of powder was determined by the
funnel method. The accurately 10 g weighed powder were
MATERIAL & METHODS taken in a funnel. The height of the funnel was adjusted in
Cefpodoxime Proxetil. CCS, Crospovidone and SSG such a way that the tip of the funnel just touches the apex of
were obtained gift samples from Cadila Pharmaceuticals the heap of the powder. The powder was allowed to flow
private limited, Dholka. through funnel freely onto the surface.The diameter of the
powder cone was measured and angle of repose was
Flow properties of Pure drug and Granules blend [7-13] calculated using the following equation.
Bulk density h
Bulk density was determined by pouring the blend into tanθ =
r
a graduated cylinder. A quantity of 10 g of powder from Where, θ = angle of repose, h = height of the cone and r =
each formulation, previously lightly shaken to break any radius of the cone base
agglomerates formed was introduced into a 50 ml
measuring cylinder. The bulk volume and mass of the Drug-excipient physical compatibility study [8,12]
powder was determined. The bulk density was calculated Differential scanning calorimetry (DSC)
by using below formula. measurements were carried out on a scanning calorimeter
Mass of powder blend (DSC Q10 V9.0 Build 275, UniversalV4.1D TA
Bulk density =
Bulk volume of powder blend Instruments). The instrument was calibrated using indium
as standard. Samples (5-10mg) were placed in sealed
Tapped density aluminium pans and heatedfrom 70oC to 160oC at a rate of
The measuring cylinder containing a known mass of 10oC/min undernitrogen atmosphere (60 ml/min), with
blend was tapped for a fixed time. The minimum volume empty pan asreference.
occupied in the cylinder and the mass of the blend was
measured. The tapped density was calculated using the Preparation of Cefpodoxime proxetil Tablet
following formula. Accurately weigh all the ingredients, Pass Lactose,
Mass of powder blend MCCP, CMC Calcium, SLS, CCS from sieve no. 40#, Mix
Tapped density = all the above sifted materials and granulate manually by
Tapped volume of powder blend
binder solution of water and PVP K30, Dry the above wet
Carr’s index mass at 60oC for 1 hours in FBD. Dried materials sift
The simplest way for measurement of free flow of through sieve 20#. Final sifting the remaining ingredients
powder is compressibility, an indication of the ease with except Cefpodoxime proxetil and aerosil, through sive no
which a material can be induced to flow is given by Carr’s 40#.Cefpodoxime proxetil and aerosil is passed through
index which is calculated as follow. Sieve no 30# and co-sift. Magnesium stearate is sifted and
Carr’s index (%) = [(TBD – LBD) × 100] / TBD kept separately.Mix all the above sifted materials with
Where, LBD = weight of the powder/volume of the powder granules in polybag except magnesium stearate than mix
TBD = weight of the powder/tapped volume of the powder the magnesium stearate at the time of compression for 5
minutes. [6,8]
Table 1: Formulation Design
Ingredients Trial 1 Trial 2# Trial 3+ Trial 3A Trial 3B Trial 3C
Cefpodoxime Proxetil 100 100 100 100 100 100
Lactose monohydrate 60 52 --- --- --- ---
Maize starch --- --- 49 49 49 49
MCCP 89 97 108 108 108 108
PVP K30 3 3 3 3 3 3
CMC Calcium 17 17 17 17 17 17
SLS 2 2 2 3 3 3
Crospovidone 2 2 2 --- --- 8
CCS 6 6 6 --- 8 ---
SSG --- --- --- 8 --- ---
Pipperment DC 117 2.5 2.5 2.5 2.5 2.5 2.5
Neotam 1 1 1 1 1 1
Aerosil 3 3 3 3 3 3
Magnesium Stearate 3 3 3 7 7 7
Water Q.S Q.S Q.S Q.S Q.S Q.S
# by compaction of API and CMC Calcium, +by compaction of API, CMC Calcium, CCS, SLS

IJPRT | January – March | 7

 Bhatt et al / International Journal of Pharmacy Research & Technology 2013 3(1) 06-10

Evaluation of Dispersible Tablets [6,8,11,12,13,14]
Weight variation[6,12,13,14]
Twenty tablets were weighed individually and the
average weight was determined. The % deviation was
calculated and checked for weight variation. Not more than
2 of the individual weight deviate from the average weight
and none deviate by more than twice of that percentage.
at 25 rpm and dropping the tablets at a height of 6 inches in
each revolution. Preweighed sample of tablets were placed
in the Friabilator and were subjected to 100 revolutions.
Tablets were deducted using a soft muslin cloth and
reweighed. The friability (f) is given by the formula.
Initial wt. of tablets − Final wt. of tablets
% loss =
Initial wt. of tablets
× 100

Thickness [6,12,13,14] Disintegration test [6,12,13,14]

The thickness of prepared tablets was measured using The device to test disintegration use is 6 glass tubes
a Verniercaliper. Five tablets from each batch were used for that are 3 inches long, open at the top and held against a 10
this test. The mean and standard deviation of each batch mesh screen at the bottom end to the basket rack assembly.
were calculated. To test for disintegration time, one tablet is placed in each
tube, and the basket rack is positioned in a 1 liter beaker of
Appearance [6,12,13,14] water, Phosphate buffer pH 6.8 at body temperature such
The general appearance and elegance of tablet was that the tablet remain 2.5 cm below the surface of the liquid
identified visually, which include tablet size, shape, colour, on their upward movement and descend not closer than 2.5
presence or absence of an odour, taste, surface texture etc. cm from the bottom of beaker. A standard motor device is
use to move the basket assembly containing the tablet up
Table 2: Physical Parameters of powder blend and down through a distance of 5-6 cm at a frequency of
Pure 28-32cycles per minute. To be in compliance with USP
Trial 1 Trial 2 Trial 3
Drug standards the tablets must disintegrate and all the particles
Bulk density must pass through 10 mesh sieve in the time specified
0.276 0.482 0.529 0.623
gm/ml
Tapped Dissolution test of optimized Trial batch: [6,8]
density 0.368 0.597 0.616 0.717 The tablets were evaluated for in vitro drug release
gm/ml was carried out using USP dissolution apparatus. The
Carr’s index following conditions were applied. For dispersible
25% 14% 13% 11% tabletUSP Dissolution apparatus Type II (Paddle) Media
%
Hausners Phosphate buffer pH 6.8 Volume of dissolution medium
1.33 1.17 1.14 1.11 900ml Speed of paddle rotation 50 RPM temperature 37.0 ±
ratio
0.5°C Sampling point 5, 10, 15, 30, 45, & 60 min interval,
Hardness [6,12,13,14] 5ml sample withdrawn and further diluted. The absorbance
Tablet hardness (tablet crushing strength) is defined as was taken at 257 nm determined by UV (shimadzu-1800).
the force required for breaking a tablet in a diametric
compression test. Tablets required a certain amount of Stability study
hardness or strength to withstand mechanical shocks of The stability study was carried out for optimized
manufacturing, packaging, and shipping. Hardness of the 5 formulation as per ICH guidelines (Feb. 2003). Various
tablets from each batch was measured using Monsanto ICH storage conditions are available which are as 25⁰C ±
hardness tester. 2⁰C (60% ± 5%RH), 30⁰C ± 2⁰C (65% ± 5%RH) and 40⁰C
± 2⁰C (75% ± 5%RH). The Cefpodoxime proxetil DT of
Friability[6,12,13,14] the best formulation were placed in screw capped glass and
Friability test is performed to assess the effect of stored at various ICH storage condition for a period of 60
friction and shocks, which may often cause tablet to chip, days. The samples were analyzed for physical appearance,
cap or break. Friability of the tablets was determined using Disintegrating Time and for the % CDR at regular interval
Roche Friabilator (Erection and Instrumentation of 15 day.[17]
Engineers). This device subjects the tablets to the combined
effect of abrasions and shock in a plastic chamber revolving

Table 3: Post-compression Parameters of formulated tablets characteristics

Properties Trial 1 Trial 2 Trial 3 Trial 3A Trial 3B Trial 3C
Thickness (mm) 3.81-3.84 3.82-3.85 3.81-3.85 4.81-4.84 4.82-4.85 4.91-5.00
Hardness Kg / cm2 4-6 5-7 5.5-6 6-8 5-7 4-6
D.T. (min) 8 12 1.5 2 54 20
% Friability 0.7 0.78 0.75 0.67 0.8 0.55
Avg. Wt. 300mg 300mg 300mg 300mg 300mg 300mg

RESULTS AND DISCUSSION
The taste of the Cefpodoxime proxetil was checked
and it was found very bitter, odour found pungent and
colour was found yellowish white.The angle of repose for
the Cefpodoxime Proxetil found 460.It is compared with
which indicates poor flow property.The bulk density for
Cefpodoxime proxetil was found 0.276gm/ml. The tapped
density for Cefpodoxime proxetil was found 0.368gm/ml.
The Carr’s index for Cefpodoxime proxetil found 25.00%.
It is compared with which indicates poor flow property.
The Hausner’s ratio for Cefpodoxime proxetil found to
1.33, It is compared with which indicates poor flow
property. The angle of repose for the physical mixture of
Cefpodoxime proxetil found in range 200 to 250.The bulk

8 | IJPRT | January – March

 Bhatt et al / International Journal of Pharmacy
rmacy Research & Technology 2013 3(1)
3 06-10

density for the physical mixture of Cefpodoxime proxetil
was found in range 0.482gm/ml to 0.623gm/ml.The tapped
density for the physical mixture of Cefpodoxime proxetil
was found in range0.597gm/ml to 0.717gm/ml. The Carr’s
index for the physical mixture of the Cefpodoxime Proxetil
was found in range 11% to 14%. The Hausner’s ratio for
the physical mixture of the Cefpodoxime proxetil was
found in range 1.11 to 1.17. It shows that the improved
flow property of the Cefpodoxime proxetil after granulation
technique and different formulation used in three trial.
From Trial-1 using granules,Trial-22 using granules and
compaction of API and CMC Calcium, Trial-3 Trial using
granules and compaction of API, CMC calcium, CCS,
SLS.The
.The bulk density, tapped density, carr’s
index,hausner’s ratio and angle of repose of the trial 3
shows the excellent flow property when compared to
others.
(CIPLA) and Altipod (Torrent). There were no much more
differences found in all 3 compared tablets in Shape,
hardness, taste, colour and % friability but D.T. was
minimum of optimized formulation i.e. 20 secs comparing
to Ceforox (CIPLA) 54 secs and Altipod Altip (Torrent) 1.1
mins. So it proves Trial-3C3C was formulation which shows
better disintegration time of Cefpodoxime Proxetil
Dispersible Tablet than the marketed brands.
In-vitro
vitro Dissolution profile of all batches. The in- vitro
dissolution profile of optimized
mized batch Trial-3C
Trial shows 99.98
.5 % CDR within just 40 to 55 mins of time which is
impacting that Crosspovidone fast disintegrating agent
comparing to SSG and CCS.

Table 4: Comparison of Optimized Formulation Trial-

Trial
3C with marketed Dispersible Formulations
Parameters Ceforox Altipod Trial 3C
Avg. Wt. 300 mg 300 mg 300 mg
4.13
4.13-
Thickness (mm) 3.9-3.93 4.91-5.00
4.15
Hardness kg/cm2 5.5 4.5 4.2
Figure 2: Dissolution Profile of all Formulations.
% Friability 0.55% 0.60% 0.50%
D.T. (sec) 54 1.1 20

Post-Compression Parameters
Post-compression
compression parameters show all batches was
evaluated for Thickness, Hardneess, D.T. and % friability
and was found within I.P. limit. Trial-33 i.e. base granule-2
granule
batch shows better results having thickness 3.81-3.85
3.81 mm,
hardness 5.5-6 kg/cm2, friability 0.75% and lowest
Disintegrating Time of 1.5 mins which was found better
than other batches. So Batch Trial-33 was optimized batch
for further tableting procedure. Aboveove optimized batch
Trial-33 was further incorporated with different
Disintegrating agent viz SSG, CCS and Crosspovidone and Figure 3: Dissolution Profile of all Formulations
batches encoded as TRIAL-3A, 3A, TRIAL-3B
TRIAL andTRIAL-3C
respectively. The resultant formulation shows little CONCLUSIONS
variation in Thickness, Hardneessand
eessand % friability but In case of acute bacterial exacerbation of chronic
remarkable difference in Disintegrating Time. The bronchitis (AECB) group-A beta--haemolytic streptococcal
Disintegrating Time was found 2 Mins, 54 secs and 20 sec pharyngotonsillitis, and uncomplicated skin/skin structure
of TRIAL-3A, TRIAL-3B and TRIAL--3C respectively and infections itrequire immediate release of drug from the
further proceed for evaluating. dosageform, which make Cefpodoxime proxetil suitable
candidate for dispersible tablets. Initially the poor flow
property was improved by comparing various granulation
techniques and Trial-33 by Dry granulation MCCP, Maize
starch and PVP K30 gives satisfactory improvement in flow
properties of drug. The optimized formulation i.e. Trial-3
Trial
MCCP, Maize starch, PVP K30 was incorporated with
various Disintegrnats like SSG, CCS and Crospovidone
which is encoded as Trial-3A,3A, Trial-3B
Trial and Trial-3C
respectively. Among 3 Batches Trial-3C Trial using
Crospovidone
done was found optimized since it had expressed
Disintegrating Time of 20 sec and 99.98 ± 0.023 % CDR
within 55min and furthermore also found better when
compared with other marketed ODT of Cefpodoxime
Fig 1: D.T. Profile of All Formulations
Formulation proxetil.

Comparison of optimized Batch with Marketed ACKNOWLEDGEMENT

Preparation The authors great fully acknowledge
cknowledge Mr. Kailash
3C was compared with
The Optimized Batch Trial-3C chand Yadav and Dr, Tarachand Kumavat of Regional
marketed Cefpodoxime Proxetil brands namely Ceforox

IJPRT | January – March | 9

 Bhatt et al / International Journal of Pharmacy Research & Technology 2013 3(1) 06-10
College of Pharmacy, Jaipur, Rajasthan and Mr Dipak
Bhatt of Cadila Pharmaceutical LTD, Dholka, Gujarat.
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