Design, evaluation and study of effect of hydrophilic

polymers on release rate of antiulcer floating tablets

BV Akbari1, RB Dholakiya1, BG Shiyani1, DJ Lodhiya1, CS Shastry2

1
 Department of Pharmaceutics, Shree Dhanvantary Pharmacy College, Kim, Surat, Gujarat,
India
2
 Department of Pharmacology, Shree Dhanvantary Pharmacy College, Kim, Surat, Gujarat,
India

Date of Web 25-Jan-

Publication 2010

       

Correspondence Address:
B V Akbari
Department of Pharmaceutics, Shree Dhanvantary Pharmacy College, Kim, Surat, Gujarat 
India

DOI: 10.4103/0975-1483.59318

   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 floating, 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 efficacy of drugs to reduce acid secretion. This study aim to
formulate floating 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 floating
tablets of famotidine containing HPMCK100M and Xanthan gum provide better
options for controlled release action and improved bioavailability.

Keywords: Famotidine, HPMC K4M, HPMC K100M, xanthan gum,

swelling index

How to cite this article:

Akbari BV, Dholakiya RB, Shiyani BG, Lodhiya DJ, Shastry CS. Design, evaluation
and study of effect of hydrophilic polymers on release rate of antiulcer floating
tablets. J Young Pharmacists 2009;1:305-11

How to cite this URL:

Akbari BV, Dholakiya RB, Shiyani BG, Lodhiya DJ, Shastry CS. Design, evaluation
and study of effect of hydrophilic polymers on release rate of antiulcer floating
tablets. J Young Pharmacists [serial online] 2009 [cited 2010 Nov 12];1:305-11.
Available from: http://www.jyoungpharm.in/text.asp?2009/1/4/305/59318

   Introduction  

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

The hydrodynamic balanced system (HBS), also called Floating drug delivery system
(FDDS), is an oral dosage form (capsule or tablet) designed to prolong the residence
time of the dosage form within the GIT. It is a formulation of a drug with gel forming
hydrocolloids meant to remain buoyant in the stomach contents. Drug dissolution
and release from the dosage form retained in the stomach fluids occur at the pH of
the stomach under fairly controlled conditions. [2] The retentive characteristics of the
dosage form are not significant for the drugs that:

1. Are insoluble in intestinal fluids

2. act locally

exhibit site-specific absorption. 

   Materials and Methods  

Famotidine and Xanthan gum was gifted from Micro lab Hosur, HPMC K4 and
HPMC K100 was gifted by Colorcon Asia Pvt. Ltd., Goa. Avicel PH-102 was
obtained as gift sample from signet Chem Ltd, Mumbai and other reagents were
obtained from the laboratory. 

Preparation of gastro retentive floating tablets

Different tablet formulations were prepared by direct compression technique. All the
powders were passed though 60 mesh sieve. The required quantity of drug, and low-
density polymer were mixed thoroughly. Talc and magnesium stearate were finally
added as glidant and lubricant respectively. The blend was directly compressed
(9mm diameter punches) using tablet compression machine. Each tablet contained
40mg of famotidine and others pharmaceutical ingredients used as shown in [Table
1].

Evaluation of powder blend [5],[6],[7],[8] 

Angle of repose: The angle of repose of powder blend was determined by the funnel
method. The accurately weighed powder blend was taken in the funnel. The height
of the funnel was adjusted in such a way that the tip of the funnel just touched the
apex of the powder blend. The powder blend was allowed to flow through the funnel
freely on to the surface. The diameter of the powder cone was measured and angle
of repose was calculated using the following equation.
tan θ = h/r

Where, h and r are the height and radius of the powder cone.

Bulk Density: Both loose bulk density (LBD) and tapped bulk density (TBD) were
determined. A quantity of 2 gm of powder blend from each formula, previously
shaken to break any agglomerates formed, was introduced in to a 10 ml measuring
cylinder. The initial volume was noted and the cylinder was allowed to fall under its
own weight on to a hard surface from the height of 2.5 cm at second intervals.
Tapping was continued until no further change in volume was noted. LBD and TDB
were calculated using the following equations.

LBD= Weight of the powder blend/Untapped Volume of the packing

TBD=Weight of the powder blend/Tapped Volume of the packing

Compressibility Index: The Compressibility Index of the powder blend was

determined by Carr's compressibility index. It is a simple test to evaluate the LBD
and TBD of a powder and the rate at which it packed down. The formula for Carr's
Index is as below:

Carr's Index (%) = [(TBD-LBD) x100]/TBD 

Total Porosity: Total porosity was determined by measuring the volume occupied by
a selected weight of a powder (V bulk ) and the true volume of the powder blend (The
space occupied by the powder exclusive of spaces greater than the intermolecular
spaces, V)

Porosity (%) =V bulk -V/V bulk x 100

Evaluation of Tablets

Drug content [9] 

Five tablets were weighed individually and powdered. The powder equivalent to
average weight of tablets was weighed and drug was extracted in 0.1 N HCl; the
drug content was determined measuring the absorbance at 266.2 nm after suitable
dilution using a Shimadzu UV-1601 UV/Vis double beam spectrophotometer.

Friability test 

The friability of tablets was determined using Roche Friabilator. It is expressed in

percentage (%). Ten tablets were initially weighed (W initial ) and transferred into
friabilator. The friabilator was operated at 25rpm for 4 minutes or run up to 100
revolutions. The tablets were weighed again (W final ). The % friability was then
calculated by -

%F = 100 (1-W 0 /W) % Friability of tablets less than 1% are considered acceptable. 

In vitro buoyancy studies [10] 

The in vitro buoyancy was determined by floating lag time method described by
Dave B.S. [10] The tablets were placed in a 250 ml beaker containing 0.1 N HCl. The
time required for the tablets to rise to the surface and float was determined as
floating lag time. The time between introduction of dosage form and its buoyancy in
0.1 N HCl and the time during which the dosage form remain buoyant were
measured. The time taken for dosage form to emerge on surface of medium called
Floating Lag Time (FLT) and total duration of time by which dosage form remain
buoyant is called Total Floating Time (TFT).

In Vitro dissolution studies [4] 

The release rate of famotidine from floating tablets was determined using the United
States Pharmacopoeia (USP) XXIV dissolution testing apparatus II (paddle method).
The dissolution test was performed using 900 ml of 0.1 N HCl, at 37 ± 0.5°C and 75
rpm. A sample (5 ml) of the solution was withdrawn from the dissolution apparatus
hourly for eight hours, and the samples were replaced with fresh dissolution medium.
The samples were diluted to a suitable concentration with 0.1N HCl. Absorbance of
these solutions was measured at 266.2 nm using a Shimadzu UV-1601 UV/Vis
double beam spectrophotometer. Cumulative percentage of drug release was
calculated using the equation obtained from a standard curve. 

Swelling index [11] 

The swelling index of tablets was determined n 0.1 N HCl (pH 1.2) at room
temperature. The swollen weight of the tablets was determined at predefined time
intervals. The swelling index was calculated by the following equation:

Swelling index WU = (W 1 - W 0 )/ W 0 x 100

Where, W t = Weight of tablet at time t.

W 0 = Initial weight of tablet

Effect of hardness on buoyancy lag time

Formulation FT10 was selected to study the effect of hardness on buoyancy lag
time. The tablets of batch 10 were compressed at different compression pressures to
get the hardness of 5kg/cm 2 , 6kg/cm 2 , 7kg/cm 2 , 8kg/cm 2 and 9kg/cm 2 . The
tablets were evaluated for buoyancy lag time. The method followed is same as that
of buoyancy test.

Stability study [12],[13],[14] 

Gastro retentive tablets of famotidine formulated in the present study were subjected
to accelerated stability studies. Stability studies of the prepared formulations were
performed at ambient humidity conditions, at room temperature, at 40 o c and 4 o c for
a period up to 30 days. The samples were withdrawn after periods of 15 days and 30
days; analyzed for its appearance, hardness, friability, floating time, drug content and
in vitro release.

   Results and Discussion  

Evaluation of tablet formulations

Pre-compression parameters

a. Angle of Repose (θ): The angle of repose for the formulated blend was carried
out. It concludes all the formulations blend were found to be in the range
24 0 .88' to 29.30'.
 b. Compressibility Index: Compressibility index was carried out and found to be
12.34% to 16.30% indicating the powder blend has the required flow property
for compression.

Post-compression parameters

a. Friability Test: The % friability was less than 1% in all the formulations
ensuring that the tablets were mechanically stable.
b. Drug Content Uniformity: The percentage of drug content for FT1 to FT10 was
found to be in between 97.11% to 99.69% of famotidine, it complies with
official specifications as shown in [Table 2].

In vitrobuoyancy study

On immersion in 0.1N HCl solution pH (1.2) at 37 0 C, the tablets floated, and
remained buoyant without disintegration. From the results it can be concluded that
the batch containing only HPMC polymer showed good total floating time (TFT).
Formulation containing HPMC K4M, HPMC K100M and Xanthan gum showed good
FLT of 45 sec, while the formulation containing Xanthan gum (alone) did not float
more than 1.5 hrs. This may be due to the nature of polymer and gas generating
agent, which were kept constant in the present study. The gas generated cannot be
entrapped inside the gelatinous layer, and it escapes leading to variation in FLT and
TFT. 

Swelling study

Swelling study was performed on all the batches (FT1 to FT10) for five hours. The
results of swelling index were shown in [Table 3] and in[Figure 1].

In the present study, the higher swelling index was found for tablets of batch FT10
containing HPMC K4M, HPMC K100M and Xanthan gum having nominal viscosity of
more than 1, 04,000 cps. Thus, the viscosity of the polymer had major influence on
swelling process, matrix integrity, as well as floating capability, hence from the above
results it can be concluded that linear relationship exists between swelling process
and viscosity of polymer. 

Effect of hardness on buoyancy lag time

The effect of hardness on buoyancy lag time for batch FT10 was studied. The results
of floating lag time of tablets with hardness of 4 kg/cm 2 , 5kg/cm 2 , 7kg/cm 2 and 8
kg/cm 2 were 47,58,76,89 and 186 sec respectively as shown in [Table 4] and.
Buoyancy lag time (sec) vs. hardness (kg/cm 2 ) plotted and shown in [Figure 2].

In vitro dissolution study and kinetic modeling of drug release

From the in vitro dissolution data it was found that formulation FT1 to FT9 released
more than 90% of drug before eight hours of the study indicating that the polymer
amount is not sufficient to control the drug release. While FT8 and FT10 containing
Xanthan gum and HPMC K100M released more than 90% of drug with in eight
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
for different formulations. The results obtaining in vitro release studies were plotted
in different models of data treatment as follows: zero order rate kinetics, first order
rate kinetics, Higuchi's classical diffusion equation, Peppas exponential equation,
Hixson-Crowell erosion equation. The kinetic values obtained for formulation FT10
were shown in [Table 6]. 

Stability study

The stability study results obtained were shown in [Table 7] and [Table 8]. The results
revealed that no significant changes in appearance, floating time, drug content,
hardness, friability, and in vitro release for FT10 formulation when it was stored at
the three different storage conditions.

   Conclusion  

The aim of the study was to study the effect of various hydrophilic polymers on in
vitro release rate from gastro retentive floating tablet of famotidine based on a low
density polymer. 

Different types of matrix forming polymers - HPMC K4 M, HPMC K100 M, Xanthan

gum were studied. The tablets eroded upon contact with the release medium, and
the relative importance of drug diffusion, polymer swelling and tablet erosion for the
resulting release patterns varied significantly with the type of matrix former. The
release rate could effectively be modified by varying the ''matrix-forming polymer/low
density polymer'' ratio, the tablet geometry (radius), the type of matrix-forming
polymer, the use of polymer blends and the addition of water-insoluble fillers (such
as Avicel PH-102). The floating behavior of the low density drug delivery systems
could successfully be combined with accurate control of the drug release patterns.
The batch optimization was done using HPMC K4M, HPMC K100 M and Xanthan
gum as matrixing polymers as they gave optimum FLT as well as long acting effect
and no/ least eroding effect. It was also found that the tablet formulations released
more than 90% drug in 8 hours as desired.

The use of HPMC K4 M, HPMC K100 M polymer in matrix tablets as density

reducing agents has given a different look, Xanthan gum was used as release
retardant polymer. During the study with the polymer various characteristics of the
material observed include: highly porous spherical structure, good compressibility,
good flow property with drug and other polymers, no significant effect on drug
release and compatibility with drug and other polymers as seen through IR spectra. 

Thus the above studies reveals that HPMC K4M, HPMC K100 M and Xanthan gum
can be successfully used in the formulation of famotidine sustained release gastro
retentive floating drug delivery system using low density polymer.

   Acknowledgment  

We are sincerely thankful to Shree Dhanvantary Pharmacy College, Kim, Surat for
provided us infrastructure facilities and moral support to carried out this research
work. I sincerely express my gratitude to Micro lab Hosur for providing Famotidine
and Xanthan gum as a gift sample. My colleagues And I are also grateful to Colorcon
Asia Pvt. Ltd., Goa and Signetchem, Mumbai, for providing us HPMC K4M, HPMC
K100M and Avicel PH-102 respectively.[18]

 
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