Pharmaceutics

Design, Evaluation and Study of Effect of Hydrophilic Polymers

on Release Rate of Antiulcer Floating Tablets
Akbari BV, Dholakiya RB, Shiyani BG, Lodhiya DJ, Shastry CS1
Departments of Pharmaceutics and 1Pharmacology, Shree Dhanvantary Pharmacy College, Kim, Surat,
Gujarat, India

Address for correspondence: Mr. Akbari Bhavesh V; E-mail: bhavesh_akbari2003@yahoo.com

ABSTRACT

Gastro retentive drug delivery systems are the systems which are retained in the stomach for a longer period
of time and thereby improve the bioavailability of drugs. Different approaches for gastro retentive dosage forms
include oating, raft, expanding/swelling, bioadhesive/ mucoadhesive and high/low density systems.Famotidine,
an anti-ulcer drug, suffers from poor bioavailability (50% as famotidine is less soluble in alkaline pH. Famotidine
used in combination with antacids promotes local delivery of these drugs to the receptor of the parietal cell
wall. Local delivery also increases bioavailability at the stomach wall receptor site and increases the efcacy of
drugs to reduce acid secretion. This study aim to formulate oating tablets of famotidine using an effervescent
approach for gastroretentive drug delivery system. Floating tablets were prepared using direct compression
techniques using polymers like HPMC K4M and HPMCK100M for their gel-forming properties. The HPMC
polymer alone is unable to control release rate. It releases drug >90% in four to six hours. In combination with
Xanthan gum it release >90% in eight hours. The results indicate that gas generated gastroretentive oating
tablets of famotidine containing HPMCK100M and Xanthan gum provide better options for controlled release
action and improved bioavailability.

Key words: Famotidine, HPMC K4M, HPMC K100M, xanthan gum, swelling index

DOI: 10.4103/0975-1483.59318

INTRODUCTION part of the small intestine; once the drug passes down the
absorption site, the remaining quantity goes unabsorbed.
Effective oral drug delivery may depend upon several factors The gastric emptying of dosage forms in humans is affected
such as gastric emptying process, gastrointestinal transit by several factors because of which wide inter and intra-
time of dosage form, drug release from the dosage form subject variations are observed.[1] Since many drugs are well
and site of absorption of drugs. Most of the oral dosage absorbed in the upper part of the gastrointestinal tract, such
forms possess physiological limitations such as variable high variability may lead to non-uniform absorption and
gastrointestinal transit, because of variable gastric emptying, makes the bioavailability unpredictable. Hence a benecial
leading to non-uniform absorption proles, incomplete delivery system would be one which possesses the ability
drug release and shorter residence time of the dosage form to control and prolong the gastric emptying time and can
in the stomach. This leads to incomplete absorption of deliver drugs in higher concentrations to the absorption site
drugs having absorption window, especially in the upper (i.e. upper part of the small intestine).

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The hydrodynamic balanced system (HBS), also called Bulk Density: Both loose bulk density (LBD) and tapped
Floating drug delivery system (FDDS), is an oral dosage bulk density (TBD) were determined. A quantity of 2 gm
form (capsule or tablet) designed to prolong the residence of powder blend from each formula, previously shaken
time of the dosage form within the GIT. It is a formulation to break any agglomerates formed, was introduced in to
of a drug with gel forming hydrocolloids meant to remain a 10 ml measuring cylinder. The initial volume was noted
buoyant in the stomach contents. Drug dissolution and and the cylinder was allowed to fall under its own weight
release from the dosage form retained in the stomach uids on to a hard surface from the height of 2.5 cm at second
occur at the pH of the stomach under fairly controlled intervals. Tapping was continued until no further change
conditions.[2] The retentive characteristics of the dosage in volume was noted. LBD and TDB were calculated using
form are not signicant for the drugs that: the following equations.
1. Are insoluble in intestinal uids
2. act locally LBD= Weight of the powder blend/Untapped Volume
of the packing
exhibit site-specic absorption.
TBD=Weight of the powder blend/Tapped Volume of
the packing
MATERIALS AND METHODS
Compressibility Index: The Compressibility Index of the
Famotidine and Xanthan gum was gifted from Micro powder blend was determined by Carrs compressibility
lab Hosur, HPMC K4 and HPMC K100 was gifted by index. It is a simple test to evaluate the LBD and TBD of a
Colorcon Asia Pvt. Ltd., Goa. Avicel PH-102 was obtained powder and the rate at which it packed down. The formula
as gift sample from signet Chem Ltd, Mumbai and other for Carrs Index is as below:
reagents were obtained from the laboratory.
Carrs Index (%) = [(TBD-LBD) x100]/TBD
Preparation of gastro retentive oating tablets
Total Porosity: Total porosity was determined by measuring
Different tablet formulations were prepared by direct the volume occupied by a selected weight of a powder
compression technique. All the powders were passed (Vbulk) and the true volume of the powder blend (The space
though 60 mesh sieve. The required quantity of drug, occupied by the powder exclusive of spaces greater than
and low-density polymer were mixed thoroughly. Talc the intermolecular spaces, V)
and magnesium stearate were nally added as glidant and
lubricant respectively. The blend was directly compressed Porosity (%) =Vbulk-V/Vbulk x 100
(9mm diameter punches) using tablet compression
machine. Each tablet contained 40mg of famotidine and Evaluation of Tablets
others pharmaceutical ingredients used as shown in Table 1.
Drug content[9]
Evaluation of powder blend[5-8]
Five tablets were weighed individually and powdered. The
Angle of repose: The angle of repose of powder blend powder equivalent to average weight of tablets was weighed
was determined by the funnel method. The accurately and drug was extracted in 0.1 N HCl; the drug content
weighed powder blend was taken in the funnel. The height was determined measuring the absorbance at 266.2 nm
of the funnel was adjusted in such a way that the tip of after suitable dilution using a Shimadzu UV-1601 UV/Vis
the funnel just touched the apex of the powder blend. double beam spectrophotometer.
The powder blend was allowed to ow through the funnel
freely on to the surface. The diameter of the powder cone Friability test
was measured and angle of repose was calculated using the
following equation. The friability of tablets was determined using Roche
Friabilator. It is expressed in percentage (%). Ten tablets were
tan = h/r initially weighed (Winitial) and transferred into friabilator. The
friabilator was operated at 25rpm for 4 minutes or run up
Where, h and r are the height and radius of the powder to 100 revolutions. The tablets were weighed again (Wnal).
cone. The % friability was then calculated by

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%F = 100 (1-W0/W) % Friability of tablets less than 1% tablets was determined at predened time intervals. The
are considered acceptable. swelling index was calculated by the following equation:

In vitro buoyancy studies[10] Swelling index WU = (W1 W0)/ W0 x 100

The in vitro buoyancy was determined by oating lag Where, Wt = Weight of tablet at time t.
time method described by Dave B.S.[10] The tablets were
placed in a 250 ml beaker containing 0.1 N HCl. The time W0 = Initial weight of tablet
required for the tablets to rise to the surface and oat
was determined as oating lag time. The time between Effect of hardness on buoyancy lag time
introduction of dosage form and its buoyancy in 0.1 N
HCl and the time during which the dosage form remain Formulation FT10 was selected to study the effect of
buoyant were measured. The time taken for dosage form hardness on buoyancy lag time. The tablets of batch 10
to emerge on surface of medium called Floating Lag Time were compressed at different compression pressures to get
(FLT) and total duration of time by which dosage form the hardness of 5kg/cm2, 6kg/cm2, 7kg/cm2, 8kg/cm2 and
remain buoyant is called Total Floating Time (TFT). 9kg/cm2. The tablets were evaluated for buoyancy lag time.
The method followed is same as that of buoyancy test.
In Vitro dissolution studies[4]
Stability study[12-14]
The release rate of famotidine from oating tablets was
determined using the United States Pharmacopoeia (USP) Gastro retentive tablets of famotidine formulated in
XXIV dissolution testing apparatus II (paddle method). the present study were subjected to accelerated stability
The dissolution test was performed using 900 ml of studies. Stability studies of the prepared formulations
0.1 N HCl, at 37 0.5C and 75 rpm. A sample (5 ml) were performed at ambient humidity conditions, at room
of the solution was withdrawn from the dissolution temperature, at 40oc and 4oc for a period up to 30 days.
apparatus hourly for eight hours, and the samples were The samples were withdrawn after periods of 15 days and
replaced with fresh dissolution medium. The samples 30 days; analyzed for its appearance, hardness, friability,
were diluted to a suitable concentration with 0.1N HCl. oating time, drug content and in vitro release.
Absorbance of these solutions was measured at 266.2
nm using a Shimadzu UV-1601 UV/Vis double beam RESULTS AND DISCUSSION
spectrophotometer. Cumulative percentage of drug
release was calculated using the equation obtained from Evaluation of tablet formulations
a standard curve.
Pre-compression parameters
Swelling index[11] a. Angle of Repose (): The angle of repose for the
formulated blend was carried out. It concludes all
The swelling index of tablets was determined n 0.1 N HCl the formulations blend were found to be in the range
(pH 1.2) at room temperature. The swollen weight of the 240.88 to 29.30.

Table 1: Composition of famotidine oating tablets

Ingredients FT1 FT2 FT3 FT4 FT5 FT6 FT7 FT8 FT9 FT10
Famotidine 40 40 40 40 40 40 40 40 40 40
HPMC K4M 40 - - - 80 - 40 - 40 20
HPMC K100M - 40 - 80 - - 40 40 - 40
Xanthan gum - - 40 - - 80 - 40 40 20
Sodium bicarbonate 20 20 20 20 20 20 20 20 20 20
Citric acid (anhydrous) 10 10 10 10 10 10 10 10 10 10
PVP-K-30 20 20 20 20 20 20 20 20 20 20
Avicel PH-102 q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
Magnesium Stearate 1 1 1 1 1 1 1 1 1 1
Talc 2 2 2 2 2 2 2 2 2 2
#All quantities were in milligrams. #All the batches contained 1% w/w talc and 0.5% w/w magnesium stearate

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b. Compressibility Index: Compressibility index was Swelling study
carried out and found to be 12.34% to 16.30%
indicating the powder blend has the required ow Swelling study was performed on all the batches (FT1 to
property for compression. FT10) for ve hours. The results of swelling index were
shown in Table 3 and in Figure 1.
Post-compression parameters
a. Friability Test: The % friability was less than 1% in In the present study, the higher swelling index was found
all the formulations ensuring that the tablets were for tablets of batch FT10 containing HPMC K4M, HPMC
mechanically stable. K100M and Xanthan gum having nominal viscosity of
b. Drug Content Uniformity: The percentage of drug more than 1, 04,000 cps. Thus, the viscosity of the polymer
content for FT1 to FT10 was found to be in between had major inuence on swelling process, matrix integrity,
97.11% to 99.69% of famotidine, it complies with as well as oating capability, hence from the above results
ofcial specications as shown in Table 2. it can be concluded that linear relationship exists between
swelling process and viscosity of polymer.
In vitro buoyancy study
Effect of hardness on buoyancy lag time
On immersion in 0.1N HCl solution pH (1.2) at 370C,
the tablets floated, and remained buoyant without The effect of hardness on buoyancy lag time for batch
disintegration. From the results it can be concluded that FT10 was studied. The results of oating lag time of tablets
the batch containing only HPMC polymer showed good with hardness of 4 kg/cm2, 5kg/cm2, 7kg/cm2 and 8 kg/
total oating time (TFT). Formulation containing HPMC cm2 were 47,58,76,89 and 186 sec respectively as shown
K4M, HPMC K100M and Xanthan gum showed good in Table 4 and. Buoyancy lag time (sec) vs. hardness (kg/
FLT of 45 sec, while the formulation containing Xanthan cm2) plotted and shown in Figure 2.
gum (alone) did not oat more than 1.5 hrs. This may be
due to the nature of polymer and gas generating agent, In vitro dissolution study and kinetic modeling of
which were kept constant in the present study. The gas drug release
generated cannot be entrapped inside the gelatinous layer,
and it escapes leading to variation in FLT and TFT. From the in vitro dissolution data it was found that

Table 2: Evaluation of physical parameters of oating tablets

Tablets Weight variation test Friability Hardness Thickness Drug

Batch (%) (%) (kg/cm2) (mm) content (%)
FT1 1.75 0.92 5.6 0.47 3.08 0.2 98.02
FT2 3.52 0.72 4.5 0.63 3.16 0.010 97.01
FT3 2.15 0.91 6.4 1.27 3.14 0.012 99.53
FT4 1.56 0.86 5.1 0.03 3.12 0.06 98.01
FT5 3.54 0.79 4.3 0.83 3.16 0.011 97.04
FT6 1.42 0.86 5.10.03 3.18 0.012 98.40
FT7 2.11. 0.78 4.3 0.83 3.15 0.010 97.11
FT8 1.89 0.81 6.4 1.27 3.10 0.012 99.55
FT9 2. 56 0.96 5.1 0.03 3.11 0.06 99.01
FT10 2.04 0.75 4.3 0.83 3.200.011 99.69
# All the values are expressed as mean SE.

Table 3: Swelling Index of Tablets of Batch FT1 to FT10

Time FT1 FT2 FT3 FT4 FT5 FT6 FT7 FT8 FT9 FT10
1 hr 32 33 31 40 35 29 36 48 30 42
2 hrs 39 38 38 51 42 36 46 59 41 51
3 hrs 41 43 44 62 49 48 56 65 46 67
4 hrs 49 49 52 73 57 59 64 78 54 76
5 hrs 56 65 68 90 68 62 77 82 60 91

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Figure 1: Swelling index for tablets of batch Ft1 to Ft10 Figure 2: Plot of hardness v/s buoyancy lag time

Table 4: Effect of hardness on buoyancy lag time of

formulation FT10
Hardness in kg/cm2 Buoyancy lag time (sec)
4 47
5 58
6 76
7 89
8 186

hours. It concludes that F10 had better controlled release

than the other formulation.

The release data obtained for formulations FT1 to FT10

were tabulated in Table 5, Figure 3 shows the plot of
cumulative per cent drug released as a function of time
Figure 3: In vitro dissolution profile of batches Ft1 to Ft10 (using
dissolution apparatus) for different formulations. The results obtaining in vitro
release studies were plotted in different models of data
formulation FT1 to FT9 released more than 90% of drug treatment as follows: zero order rate kinetics, rst order
before eight hours of the study indicating that the polymer rate kinetics, Higuchis classical diffusion equation, Peppas
amount is not sufcient to control the drug release. While exponential equation, HixsonCrowell erosion equation.
FT8 and FT10 containing Xanthan gum and HPMC The kinetic values obtained for formulation FT10 were
K100M released more than 90% of drug with in eight shown in Table 6.

Table 5: In vitro cumulative % drug release of all batches by paddle method

Time (hrs) Cumulative % drug release

FT1 FT2 FT3 FT4 FT5 FT6 FT7 FT8 FT9 FT10
0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
1 49.19 40.30 37.41 31.44 46.66 34.51 39.47 26.66 30.66 27.09
2 58.92 52.35 42.36 48.91 69.47 46.85 56.52 36.59 44.31 45.68
3 87.47 65.94 57.71 66.18 76.41 56.61 68.48 51.56 57.96 65.51
4 99.68 76.14 67.49 79.62 81.56 64.17 71.83 67.34 63.49 77.48
5 - 89.57 73.06 83.67 89.58 74.90 91.35 80.11 70.06 81.80
6 - 101.16 80.84 88.04 101.83 82.62 100.16 92.02 81.34 89.07
7 - - 90.07 100.1 - 89.98 - 100.30 92.07 98.12
8 - - 97.98 - - 95.35 - - 98.18 100.36

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Table 6: Kinetic values obtained from in vitro released signicantly with the type of matrix former. The release
data of formulation FT10 rate could effectively be modied by varying the matrix-
Kinetic model Intercept Slope R2 forming polymer/low density polymer ratio, the tablet
Zero-order plot 17.177 10.120 0.9942 geometry (radius), the type of matrix-forming polymer, the
First-order plot 4.7579 -0.4795 0.9850
Higuchi plot -3.6818 37.99 0.9880 use of polymer blends and the addition of water-insoluble
Hixson Crowell 4.7579 -0.4795 -0.9936 llers (such as Avicel PH-102). The oating behavior of
Peppas-korsmeyer 1.4767 0.6214 0.9555 the low density drug delivery systems could successfully
be combined with accurate control of the drug release
Stability study patterns. The batch optimization was done using HPMC
K4M, HPMC K100 M and Xanthan gum as matrixing
The stability study results obtained were shown in Table 7 polymers as they gave optimum FLT as well as long acting
and 8. The results revealed that no signicant changes in effect and no/ least eroding effect. It was also found that
appearance, oating time, drug content, hardness, friability, the tablet formulations released more than 90% drug in 8
and in vitro release for FT10 formulation when it was stored hours as desired.
at the three different storage conditions.
The use of HPMC K4 M, HPMC K100 M polymer
CONCLUSION in matrix tablets as density reducing agents has given a
different look, Xanthan gum was used as release retardant
The aim of the study was to study the effect of various polymer. During the study with the polymer various
hydrophilic polymers on in vitro release rate from gastro characteristics of the material observed include: highly
retentive oating tablet of famotidine based on a low porous spherical structure, good compressibility, good
density polymer. ow property with drug and other polymers, no signicant
effect on drug release and compatibility with drug and other
Different types of matrix forming polymers - HPMC polymers as seen through IR spectra.
K4 M, HPMC K100 M, Xanthan gum were studied. The
tablets eroded upon contact with the release medium, and Thus the above studies reveals that HPMC K4M, HPMC
the relative importance of drug diffusion, polymer swelling K100 M and Xanthan gum can be successfully used in
and tablet erosion for the resulting release patterns varied the formulation of famotidine sustained release gastro

Table 7: Stability studies data of formulation FT10

Time (hrs) Cumulative % drug release
Initial % At room temperature At 40 C temperature At 2-8 C temperature
drug release
After 15 days After 1 month After 15 days After 1 month After 15 days After 1 month
1 27.09 30.51 31.89 28.51 26.89 35.51 36.98
2 45.68 48.54 46.74 45.54 45.74 46.34 46.64
3 65.51 57.96 56.92 67.96 67.92 57.69 55.23
4 77.48 69.45 66.45 79.45 77.45 69.54 69.84
5 81.80 75.23 73.93 85.23 83.93 79.32 72.92
6 89.07 83.98 84.98 89.98 86.98 84.99 82.89
7 98.12 96.87 95.75 96.87 97.70 96.78 93.73
8 100.36 98.63 98.45 99.83 99.75 98.36 98.75

Table 8: Results of physical parameters after stability studies of formulation FT10

Parameters Initial At room temperature At 40 C temperature At 2-8 C temperature
After 15 days After 1 month After 15 days After 1 month After 15 days After 1 month
FLT (sec) 45 49 51 45 48 49 54
TFT (hrs) >12 >12 >12 >12 >12 >12 >12
Hardness (kg/cm2) 4.3 4.1 4.6 4.0 4.4 4.9 4.1
Friability (%) 0.75 0.78 0.81 0.75 0.75 0.65 0.74
Drug Content (%) 99.69 99.76 99.89 99.59 99.45 99.90 99.53

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