Dolas et al Journal of Drug Delivery & Therapeutics.

2018; 8(5):393-399

Available online on 15.09.2018 at [Link]

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted
non-commercial use, provided the original work is properly cited

Open Access Research Article

FORMULATION AND EVALUATION OF GASTRORETENTIVE

FLOATING TABLETS OF LAFUTIDINE
Ramdas T. Dolas *1, Dr. Shalindra Sharma2, Madhuraj Sharma3
1
Research Scholar, Jodhpur Institute of Pharmacy, Jodhpur National University, Jodhpur, India
2
Principal, Jodhpur Institute of Pharmacy, Jodhpur National University, Jodhpur, India
3
Dean Incharge, Faculty of Pharmaceutical Sciences, Jodhpur National University, Jodhpur, India

ABSTRACT
The purpose of this research was to develop a novel gastroretentive drug delivery system based on wet granulation technique for
sustained delivery of active agent. Quick GI transit could result in incomplete drug release from the drug delivery system above the
absorption zone leading to decreased efficacy of the administered dose and thus less patient compliance. Gastroretentive floating
tablets, which was designed to provide the desired sustained and complete release of drug for prolonged period of time.
Gastroretentive floating tablets of lafutidine were prepared by wet granulation technique using different concentrations of Gum
Kondagagu, Gum olibanum and Locust bean Gum. The optimized formulation (LF14) exhibited 99.54% drug release in 12 hrs,
while the buoyancy lag time was 33 sec. In-vitro drug release kinetics was found to follow both the Zero order and the possible
mechanism of lafutidine release from the optimized formulation might be attributed to super case II transport mechanism. The
Optimized formulation (LF14) showed no significant change in physical appearance, drug content, floating lag time, in vitro
dissolution studies after 75%±5% RH at 40±20C relative humidity for 6 months.
Keyword: Wet granulation, Floating lag Time, Gastroretentive, Lafutidine

Article Info: Received 30 July, 2018; Review Completed 05 Sep 2018; Accepted 06 Sep 2018; Available online 15 Sep 2018

Cite this article as:

Dolas RT, Dr. Sharma S, Sharma M, Formulation and evaluation of gastroretentive floating tablets of lafutidine,
Journal of Drug Delivery and Therapeutics. 2018; 8(5):393-399 DOI: [Link]

*Address for Correspondence:

Ramdas T. Dolas, Research Scholar, Jodhpur Institute of Pharmacy, Jodhpur National University, Jodhpur, India

INTRODUCTION bacteria and exhibit low solubility at high pH values.

Gastro retentive dosage form can remain in the gastric
Oral administration is the most versatile, convenient and region for several hours and hence significantly prolong
commonly employed route of drug delivery for systemic the gastric residence time of drugs. Prolonged gastric
action .Oral controlled release drug delivery have retention improves bioavailability, reduces drug waste,
recently been of increasing interest in pharmaceutical and improves solubility of drugs that are less soluble in a
field to achieve improved therapeutic advantages, such high pH environment. Gastro retention helps to provide
as ease of dosing administration, patient compliance and better availability of new products with suitable
flexibility in formulation. A controlled drug delivery therapeutic activity and substantial benefits for patients
system with prolonged residence time in the stomach is 1,2
.
of particular interest for drugs that are locally active in
the stomach, have narrow absorption window in Lafutidine has newly developed 2nd generation H2
gastrointestinal tract, are primarily absorbed from antihistaminic blocker. It is exceedingly helpful in
stomach and upper part of GIT, are unstable in the gastric and duodenal ulcers. It prevents the gastric
intestinal or colonic environment, disturb normal colonic mucosal lesions in both acute and chronic gastritis. The
lafutidine penetrates the stomach wall and binds the H2
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Dolas et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):393-399

receptors. The lafutidine also increases the blood flow to Methods:

gastric mucosa. It shows protective action in an
Wet Granulation Method 4
experimental model 3.
Gastroretentive floating tablets of lafutidine were
MATERIALS AND METHODS prepared by wet granulation technique using different
Materials: concentrations of Gum Kondagagu, Gum olibanum and
Locust bean Gum. All the ingredients were passed
The Lafutidine was obtained as a gift sample from through sieve no 85# and were mixed uniformly.
splendid laboratories, Pune. Gum Kondagogu, Gum Granulation was carried out with sufficient quantity of
Olibanum and Locust Bean Gum were obtained from binder solution (PVP K 30 - 5% in isopropyl alcohol).
Girijan Co-operative corp. Ltd, Hyderabad. Sodium The wet mass was passed through sieve no 12# and
bicarbonate, Citric acid, PVP-K30 was gifted from MSN dried at 450C for 2 hr. Dried granules were sized by
Labs Ltd, Hyderabad. All other chemicals used were of sieve no.18# add magnesium stearate and talc. Granules
analytical grade. obtained were compressed with 8 mm flat punch
(Cadmach, Ahmedabad, India).

Table 1: Formulation trials of floating tablets of Lafutidine using Locust bean gum
Ingredients LF1 LF2 LF3 LF4 LF5 LF6 LF7 LF8
Drug 10 10 10 10 10 10 10 10
Locust bean 30 40 50 60 30 40 50 60
gum
Sodium 30 30 30 30 45 45 45 45
Bicarbonate
Citric acid 10 10 10 10 10 10 10 10
MCC 150 140 130 120 135 125 115 105
PVP K-30 10 10 10 10 10 10 10 10
Mg stearate 5 5 5 5 5 5 5 5
Talc 5 5 5 5 5 5 5 5
Total weight 250 250 250 250 250 250 250 250

Table 2: Formulation trials of floating tablets of Lafutidine using Gum Kondagogu

Ingredients LF9 LF10 LF11 LF12 LF13 LF14 LF15 LF16
Drug 10 10 10 10 10 10 10 10
Gum Kondagogu 50 70 90 110 50 70 90 110
Sodium Bicarbonate 30 30 30 30 45 45 45 45
Citric acid 10 10 10 10 10 10 10 10
MCC 130 110 90 70 115 95 75 55
PVP K-30 10 10 10 10 10 10 10 10
Mg stearate 5 5 5 5 5 5 5 5
Talc 5 5 5 5 5 5 5 5
Total weight 250 250 250 250 250 250 250 250

Table 3: Formulation trials of floating tablets of Lafutidine using Locust bean gum
Ingredients LF17 LF18 LF19 LF20 LF21 LF22 LF23 LF24
Drug 10 10 10 10 10 10 10 10
Gum Olibanum 65 75 85 95 65 75 85 95
Sodium Bicarbonate 30 30 30 30 45 45 45 45
Citric acid 10 10 10 10 10 10 10 10
MCC 105 95 85 75 80 70 60 50
PVP K-30 10 10 10 10 10 10 10 10
Mg stearate 5 5 5 5 5 5 5 5
Talc 5 5 5 5 5 5 5 5
Total weight 250 250 250 250 250 250 250 250
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Evaluation Parameters solutions was measured at 220 nm using a UV

spectrophotometer.
Precompression parameters 5,6
Stability studies: The optimized formulation of
Prior to the compression, the formulation powder blends
lafutidine were packed in strips of 0.04 mm thick
were evaluated for their bulk and tapped density and
aluminum foil laminated with poly vinyl chloride by
from these values compressibility index and Hausner’s
strip packing and these packed formulations were stored
ratio were calculated. While the flow properties of the
in ICH certified stability chambers (Thermo labs,
powder bled were accessed from the angle of repose 4.
Mumbai) maintained at 40 0C and 75% RH for 6
Evaluation of Floating Tablets 7,8 months. The samples were withdrawn periodically and
evaluated for their floating lag time, content uniformity
Post compression parameters: The prepared tablets
and for in vitro drug release 9.
were evaluated for quality control tests like weight
variation, hardness, thickness, friability and content RESULTS AND DISCUSSION
uniformity.
In the present work, lafutidine used in the treatment of
Weight variation: Ten tablets were selected randomly ulcer has been utilized as an active drug and considered
from each batch and weighed individually, calculating to be good candidate for reducing dose frequency, for
the average weight and comparing the individual tablet solid oral sustained release formulation as well as more
weight to the average. From this; percentage weight compliance in ulcers. The present it in the form of
difference was calculated and then checked for USP gastroretentive floating tablets to provide the desired
specifications. sustained and complete release for prolonged period of
time.
Hardness and friability: Hardness of tablet was
determined by Monsanto hardness Tester. Ten tablets Precompression Parameters
were randomly picked from each batch and analyzed for
hardness. The mean and standard deviation were also The results of precompression evaluation parameters are
calculated. Friability test was done by Roche friabilator. shown in (Table 4). All the precomression evaluation
Ten tablets were weighed and were subjected to the parameters were within the USP Pharmacopoeia limits.
combined effect of attrition and shock by utilizing a Postcompression Parameters
plastic chamber that revolve at 25 rpm dropping the
tablets at distance of 6 in. with each revolution. The results of postcompression evaluation parameters
Operated for 100 revolutions, the tablets were de-dusted are shown in (Table 5). The Weight variation of all
and reweighed. The percentage friability was calculated. formulations witnessed to be in the limit allowed that is
± 5% of total tablet weight. The suitable hardness for
In vitro buoyancy studies: The in vitro buoyancy was compressed tablets is considered as a vital function for
determined floating lag time, as per the method the end user. The deliberated crushing strength of
described by Rosa et al. The tablets were placed in a 250 fabricated tablets of formulations F1-F24 trended
ml beaker, containing 200 ml of 0.1 N HCl. The time between 4.0-5.0kg/cm2. The thickness of all the
required for the tablet to rise to the surface and float was formulations ranges from 4.1-4.5 mm. The friability of
determined as Floating Lag Time (FLT) and the time all prepared formulation between 0.53-0.79 percent, the
period up which the tablet remained buoyant is friability properties limits are in between 0-1%. The
determined as Total Floating Time (TFT). drug content of all formulation is in between 94.23-
In vitro Dissolution Studies: The In vitro dissolution 99.68%, drug content depends on the angle of repose
study was performed by using a United States since the angle of repose indicates uniform flow nature
Pharmacopeia (USP) type II (paddle) apparatus at a of powder blend which makes the drug to evenly
rotational speed of 100 rpm. Exactly 900 ml of 0.1 N distribute in all the formulation and to maintain content
HCl was used as the dissolution medium and the uniformity in all batches. Tablets of all batches had
temperature was maintained at 37oC ± 0.5oC. A sample floating lag time below 60 seconds regardless of
(10 ml) of the solution was withdrawn from the viscosity and content of polymers because of evolution
dissolution apparatus at specified time interval for 12 of CO2 resulting from the interaction between sodium
hrs and the same volume was replaced with pre -warmed bicarbonate and dissolution medium, entrapment of gas
fresh dissolution media. The samples were filtered inside the hydrated polymeric matrices enables the
through a whattman filter paper and diluted to a suitable dosage form to float by lowering the density of the
concentration with 0.1 N HCl. Absorbance of these matrices. Total Floating time for the natural polymers
formulations were more than 12 hrs.

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Dolas et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):393-399

Table 4: Physical properties of prepared powder blends of Floating tablet

Formulation Bulk density Tapped density Angle of rr s e

H us er’s ratio
(g/cc) (g/cc) repose(ϴ) (%)
LF1 0.56±0.02 0.54±0.01 24.34±0.4 10.23±0.8 1.13±0.02
LF2 0.58±0.12 0.58±0.04 23.67±0.3 10.23±1.0 1.11±0.07
LF3 0.59±0.04 0.64±0.05 26.54±0.1 10.12±0.7 1.13±0.09
LF4 0.50±0.04 0.68±0.04 23.89±0.2 11.34±0.6 1.14±0.03
LF5 0.65±0.02 0.59±0.02 22.56±0.1 11.23±0.8 1.11±0.05
LF6 0.50±0.21 0.66±0.12 23.30±0.1 10.23±0.5 1.12±0.06
LF7 0.52±0.06 0.64±0.03 25.56±0.2 10.34±1.0 1.14±0.06
LF8 0.53±0.01 0.68±0.03 24.67±0.3 10.11±0.8 1.12±0.03
LF9 0.57±0.01 0.61±0.01 25.56±0.3 10.45±0.7 1.13±0.02
LF10 0.58±0.13 0.67±0.06 22.66±0.2 11.45±0.5 1.15±0.01
LF11 0.53±0.09 0.68±0.12 25.34±0.2 10.23±0.5 1.13±0.01
LF12 0.57±0.06 0.64±0.21 22.99±0.5 11.34±0.5 1.12±0.01
LF13 0.54±0.01 0.67±0.04 25.14±0.3 10.67±0.4 1.11±0.02
LF14 0.51±0.04 0.66±0.07 21.09±0.2 09.23±0.4 1.10±0.03
LF15 0.53±0.01 0.63±0.04 22.78±0.4 10.45±0.3 1.10±0.02
LF16 0.54±0.02 0.61±0.07 22.45±0.4 10.68±0.2 1.13±0.02
LF17 0.59±0.21 0.68±0.03 25.09±0.3 11.47±0.8 1.12±0.02
LF18 0.58±0.03 0.67±0.08 23.05±0.2 11.99±0.3 1.14±0.02
LF19 0.56±0.02 0.61±0.12 25.06±0.2 11.45±0.6 1.13±0.01
LF20 0.59±0.06 0.64±0.1 24.78±0.1 10.12±0.5 1.15±0.01
LF21 0.59±0.07 0.63±0.03 25.34±0.4 11.09±0.4 1.16±0.02
LF22 0.56±0.15 0.63±0.04 24.12±0.3 10.34±0.2 1.14±0.03
LF23 0.58±0.13 0.66±0.13 24.45±0.3 10.67±0.4 1.14±0.02
LF24 0.56±0.12 0.68±0.05 25.56±0.2 09.68±0.6 1.14±0.05

Table 5: Physicochemical parameters of lafutidine floating tablets

*Weight #Content Floating lag Total
F. No #Thickness #Hardness #Friability
variation uniformity time floating
(mm) (Kg/Cm2) (%)
(mg) (%) (sec) time (hrs)
F1 249.65±1.2 4.4±0.12 4.3±0.12 0.57±0.01 95.23±0.63 55 >12
F2 251.69±0.8 4.3±0.06 4.1±0.06 0.55±0.02 97.04±0.06 52 >12
F3 248.04±0.5 4.3±0.06 4.1±0.06 0.63±0.03 95.56±0.14 50 >12
F4 250.05±0.0 4.2±0.12 5.2±0.12 0.72±0.01 98.11±1.01 47 >12
F5 251.54±0.4 4.3±0.00 4.3±0.00 0.62±0.02 94.23±1.08 44 >12
F6 250.78±0.4 4.3±0.10 5.1±0.06 0.66±0.01 95.45±0.31 42 >12
F7 252.65±0.3 4.1±0.10 4.3±0.10 0.53±0.02 98.91±0.49 40 >12
F8 249.57±0.2 4.3±0.25 5.3±0.40 0.69±0.01 97.23±0.51 57 >12
F9 250.76±0.3 4.3±0.06 5.3±0.06 0.58±0.00 96.13±0.56 55 >12
F10 248.49±0.2 4.2±0.20 4.2±0.42 0.79±0.02 95.23±0.24 52 >12
F11 251.53±0.4 4.2±0.06 5.3±0.06 0.76±0.01 97.97±0.21 49 >12
F12 250.58±0.3 4.2±0.00 4.4±0.06 0.73±0.02 98.45±0.76 46 >12
F13 251.34±0.2 4.3±0.26 4.8±0.35 0.72±0.02 97.45±0.48 43 >12
F14 250.67±0.3 4.1±0.21 5.4±0.21 0.54±0.03 99.68±0.23 33 >12
F15 249.65±0.2 4.4±0.06 5.0±0.23 0.65±0.02 96.45±0.36 58 >12
F16 250.65±0.3 4.2±0.25 4.4±0.23 0.68±0.01 96.45±0.69 55 >12
F17 251.79±0.4 4.5±0.15 5.8±0.32 0.59±0.01 96.34±0.35 53 >12
F18 251.87±0.1 4.4±0.25 4.7±0.35 0.68±0.01 97.56±0.23 50 >12
F19 249.65±0.2 4.4±0.06 4.0±0.23 0.75±0.02 96.45±0.36 47 >12
F20 249.32±0.2 4.2±0.12 5.5±0.20 0.63±0.03 97.18±0.81 45 >12
F21 250.16±0.8 4.0±0.10 4.2±0.81 0.52±0.89 95.23±0.13 51 >12
F22 251.33±0.2 4.3±0.15 5.3±0.25 0.61±0.23 97.59±0.65 48 >12
F23 249.58±0.7 4.1±0.33 4.8±0.12 0.58±0.55 96.38±0.33 54 >12
F24 250.11±0.4 4.5±0.28 4.5±0.45 0.71±0.67 98.42±0.27 49 >12

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Figure 1: Comparison of in vitro Percentage drug release of lafutidine floating tablet formulations LF1-LF8

Figure 2: Comparison of in vitro Percentage drug release of lafutidine floating tablet formulations LF9-LF16

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Dolas et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):393-399

Figure 3: Comparison of in vitro Percentage drug release of lafutidine floating tablet formulations LF17-LF24
From the above figures (Figure 1, 2 and 3) it can be that mathematically interprets the dissolution curve in
observed that the polymer Gum Kondagogu has the function of some parameters related to the
sustaining effect on the release of drug from the floating formulations.
matrix tablet of lafutidine compared to Locust bean gum
A water soluble drug assimilated in a matrix is mainly
and Gum olibanum. The difference in the drug release
liberated by diffusion, while for a low water- soluble
profiles of various formulations was due to the presence
drug the self-erosion of the matrix will be the principal
of different concentrations of natural polymers. The
release mechanism. Mathematical modeling of the
concentration of polymer was added in increasing order
release kinetics of specific classes of controlled-release
to check its drug release retarding ability and LF14 was
systems may be used to predict solute release rates from
considered as best formulation among the all the
and solute diffusion behavior through polymers and
formulations. LF14 showed good buoyancy properties
elucidate the physical mechanisms of solute transport by
and sustained the drug release for desired period of time
simply comparing the release data to mathematical
(12hrs). The release profiles from all these formulations
models.
followed diffusion controlled release, complying with
higher correlation coefficient values of Higuchi and In the view of the establishment of the release
Peppas equations. mechanism and quantitatively interpreting and translate
mathematically the dissolution date being plotted.
Mathematical treatment of optimized formula of
lafutidine floating tablets CONCLUSION
In vitro dissolution has been identified as a vital part of In the present work, it can be concluded that the
drug development. It could be used for assessment of lafutidine floating tablets can be an innovative and
bioequivalence. There are several models to represents promising approach for the delivery of lafutidine for the
the drug dissolution profiles where it is a function of treatment of gastric ulcers. The optimized formulation
time associated with the amount of drug dissolved in LF14 containing Gum Kondagagu and a gas-generating
distinction to the dosage form. The quantitative agent. In-vitro release profile of lafutidine and marketed
interpretation of the values collected in the dissolution product when compared, the optimized formulation
assay is facilitated by the usage of a generic equation LF14 showed drug release of 99.54±1.26 % within 12h
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Dolas et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):393-399

whereas 99.54 % of the drug was released from the rate constant of optimized formulation LF14 was low
marketed product within 12h. The major mechanism of enough prolonging drug delivery. This result is
drug release follows zero order kinetics and non fickian encouraging, because a longer gastric residence time is
transport by coupled diffusion and erosion. This means an important condition for higher bioavailability of the
that water diffusion and also the polymer rearrangement drugs included in the prolonged or sustained release
have an essential role in the drug release. The release dosage forms.

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