IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY

Available online at www.ijrpc.com Research Article

DOI: https://dx.doi.org/10.33289/IJRPC.12.2.2022.12(24)

FORMULATION AND EVALUATION OF

FLOATING TABLETS OF TINIDAZOLE
N.V.V. Jagan Mohan Reddy*, D. Vijayalakshmi,
G. Poorna, G. Saispandana, G. Saisirisha and G. Harikamani
Department of Pharmaceutics, VJ’s College of Pharmacy,
Diwancheruvu-533296,Rajahmundry, East Godavari, Andhra Pradesh, India.

ABSTRACT
Floating matrix tablets of tinidazole were developed to prolong gastric residence time and increase drug
absorption further increasing the bioavailability. It is an anti-parasitic. Floating tablets of tinidazole
formulated to increase gastric residence and there by improve its therapeutic efficacy. By using
different polymers such as carbopol, guargum, sodium alginate, and eudragit prepare formulations f1,
f2, f3, f4, f5, f6, f7, f8, f9. Formulated tablets showed satisfactory results for various post compression
evaluation parameters like thickness, hardness, weight variation, floating lagtime, total floating time,
content uniformity and invitro drug release. Formulation f2 gave better-controlled drug release and
floating properties in comparison to the other formulations.

Keywords: Anti-parasitic, increase gastric resistance, carbopol, guargum.

INTRODUCTION
Oral route is the most convenient and extensively used route for drug administration. This route has
high patient acceptability, primarily due to ease of administration. Over the years, oral dosage forms
have become increasingly sophisticated with major role being played by controlled release drug delivery
systems (crdds) release drug at predetermined rate.
Drug delivery technologies are advanced enough to design any dosage form that can deliver drugs at
a constant rate for extended periods of time ranging from days to years. And yet most oral controlled
release dosage forms deliver drugs for only 12hrs.Oral delivery for 24hrs is possible for some drugs;
such are absorbed well throughout gastro intestinal tract (git). Thus, the real issue in the development
of oral controlled release dosage forms is how to extend the time for drug absorption from final intestine.
For example, oral dosage forms may have to stay in the stomach or somewhere in the upper small
intestine until the entire drug is released for desired period of time. Designing platforms that target upper
small intestine is rather difficulty, since they would have to be adhesive type systems that selectively
adhere to jejunum, ileum surface. However, it is difficult to place oral dosage form sat selected sites in
the small intestine. For this reason, research efforts have been focused on platform to extend gastric
retention time (grt).
Oral drug delivery is the most widely utilized route of administration among all the routes that have been
explored for systemic delivery of drugs via pharmaceutical products of different dosage forms. Oral
route is considered most natural, uncomplicated, convenient and safe due to its ease of administration,
patient acceptance and cost-effective manufacturing process.

GASTRORETENTIVE DRUG DELIVERY SYSTEMS

The development of oral crdds has been hindered by the inability to localize the system in the selected
regions of the git. There has been considerable research over the last decade on the possibility of
controlled and site specific delivery to the git by controlling the gastro intestinal transit of orally
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

administered dosage forms using gastro retentive drug delivery systems (grdds).Such grdds possess
the ability of retaining the druging it particularly in the stomach for long periods (s.S.davis 2005).
The idea of gastro retention stems from the need to localize drugs at specific region ofgit such as
stomach in the body. Often the extent of drug absorption is limited by the residence time of the drug at
absorption site. The transittime in giti. e., from the mouth to anus, varies from one person to another. It
also depends upon the physical properties of the object ingested and the physiological conditions of the
alimentary canal. In addition, the relatively brief g.i. transittime (8-12 hr) for most of the drugs impedes
the formulation of once daily dosage form. Many drugs show poor bioavailability (ba) in the presence
of intestinal metabolic enzymes like cytochromep450 (cyp3a), abundantly present in the intestinal
epithelium. Their activity decreases longitudinally along the small intestine, with levels rising slightly
from the duodenum to the jejunum and declining in the ileum and colon. This non uniform distribution
of cyp3a causes regional variability in the absorption of drugs that are the substrates of enzymes.

FLOATING DDS (FDDS)

Floating systems, first described by davies in1968, have a bulk density lower than the gastric content.
They remain buoyant in the stomach for a prolonged period of time, with the potential for continuous
release of drug. Eventually, the residual system is emptied from the stomach. Gastric emptying is much
more rapid in the fasting state and floating systems rely heavily on the presence of food to retard
emptying and provide sufficient liquid for effective buoyancy. In 1985, mojaverian et al. Reported that
the amount, nature and caloric content of the food .The main drawback is the passivity of the operation.
It depends on the air sealed in the dry mass centre following hydration of the gelatinous surface layer
and hence the characteristics and amount of polymer (hwang.S. J1998)

Classification of FDDS
Based on the mechanism of buoyancy, floating systems can be classified into two distinct categories
A. Non-effervescentsystems.11-14.
B. Effervescentsystems.15,16.

A. Non-effervescent systems
1. Hydrodynamically balanced systems (HBS)

Fig. 1: Hydrodynamically balanced systems

The gelatinous polymer barrier formation results from hydrophilic polymer swelling. Drug is
released by diffusion and erosion of the gel barrier.
The HBS must comply with three manor criteria L.J. Caldwellet al 1988
1. It must have sufficient structure to form a cohesive gel barrier
2. Itmustmaintainanoverallspecificgravitylowerthanthatofgastriccontentsi.e.,1.004-1.01g/ml
3. It should dissolve slowly enough to serve as are servoir for the delivery system

A bilayer tablet canalso be prepared to contain one immediate-release and other sustained-release
layer. Immediate-release layer delivers the initial dose whereas SR layer absorbs gastric fluid and
forms a colloidal gel barrier on its surface Shethetal 1978.
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Fig. 2: Improvement in HSB

The main drawback is the passivity of the operation. It depends on the air sealed in the dry mass centre
following hydration of the gelatinous surface layer and hence the characteristics and amount of polymer
(Hwang.S. J 1998).

2. Intra gastric floating drug delivery device

The device comprised of a drug reservoir encapsulated in a microporous compartment having
pores along its top and bottom surfaces. The peripheral walls of the drug reservoir compartment
were completely sealed to prevent any physical contact of the undissolved drug with the stomach
walls. The floatation chamber caused the system to float in the gastric fluid Yuasa.Hetal1996, developed
intra gastric floating SR granules of diclofenac sodium using polymer solution of
hydroxypropylcellulose L grade(HPC-L) and ethylcellulose, and calcium silicate as a floating
carrier, which has a characteristically porous structure with numerous pores and alarge individual
pore volume. The coated granules acquired floating ability from the air trapped in the pores of
calcium silicate when they were coated with a polymer(Singh. Brahma N.,Kwon H.Kim2000).

Fig. 3: Intra gastric floating drug delivery device

3. Floating tablets
Single-unit floating tablets prepared based on polypropylene foam powder and matrix-forming polymer.
Incorporation of highly porous foam powder in matrix tablets provided density much lower than the
density of the release medium. A 17% wt/wt foam powder (based on mass of tablet) was achieved in
vitro for at least 8 hours. It was concluded that varying the ratios of matrix-forming polymers and the
foam powder could alter the drug release patterns effectively(Shweta Arora etal 2005 & Streubel Aet
al2003)

4. Floating Microspheres
Conventionally, the drug-loaded microspheres have been developed by emulsification and solvent-
evaporation method. Example was preparation of hollow microspheres (microballoons), loaded with
ibuprofen in their outer polymer shell. The ethanol-dichloromethane solution of the drug and an enteric
acrylic polymer was poured into an agitated aqueous solution of PVA that was thermally controlled at
40oC. The gas phase generated in dispersed polymer droplet by evaporation
ofdichloromethaneformedaninternalcavityinmicrospheresofpolymerwithdrug.The micro balloons floated
continuously over the surface of acidic dissolution media containing surfactant for greater than 12 hr in
vitro.

Fig. 4: Floating Microspheres

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B. Effervescent systems or Gas generating systems

ADDS can be made to float in the stomach by incorporating a floating chamber with may be filled with
vacuum, air or inert gas. The gas in the floating chamber can be introduced either by the effervescent
reaction between organic acids and bicarbonate salts or by the volatilization of an organic solvent.

1. Effervescent reaction Tablets

Floatability can also be achieved by generation of gas bubbles. CO2 can be generated in situ by
incorporation of carbonates or bicarbonates, which react with acid—either the natural gastric acid or
co-formulated as citric or tartaric acid. The optimal stoichiometric ratio of citric acid and sodium
bicarbonate for gas generation.

Fig. 5: Formation of CO2 in gas generating systems

Beads
Floating alginate beads using gas forming agents (calcium carbonate and sodium bicarbonate) and
studied the effect of CO2 generation on the physical properties, morphology, and release rates. The
study revealed that the kind and amount of gas-forming agent had a profound effect on the size, floating
ability, pore structure, morphology, release rate, and mechanical strength of the floating beads. It was
concluded that calcium carbonate formed smaller but stronger beads than sodium bicarbonate. Calcium
carbonate was shown to be a less-effective gas-forming agent than sodium bicarbonate but it produced
superior floating beads with enhanced control of drug release rates. In vitro floating studies revealed
that the beads free of gas-forming agents sank uniformly in the media while the beads containing gas-
forming agents in proportions ranging from 5:1 to 1:1 demonstrated excellent floating (100%)20.

Fig. 6: Effervescent Beads

2. Volatile liquid containing systems

The GRT of a DDS can be sustained by incorporating an inflatable chamber, which contains a liquid
i.e., ether, cyclopentane, that gasifies at body temperature to cause the inflation of the chamber in the
stomach, shown in (Fig. 7).
Two patents on FDDS issued to the Alza Corporation disclosed drug delivery devices for the controlled
and continuous administration of medicinal agents.
These Gastro-inflatable drug delivery devices are osmotically controlled floating systems containing
a hollow deformable unit that can convert from a collapsed to an expanded position, and returns to the
collapsed position after an extended period. The deformable system consists of two chambers
separated by an impermeable, pressure-responsive, movable bladder. The first chamber contains the
drug and the second chamber contains the volatile liquid.
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

The device inflates, and the drug is continuously released from the reservoir into the gastric fluid. The
device may also consist of a bioerodible plug made up of PVA, polyethylene etc. that gradually dissolves
causing the in flatable chamber to release gas and collapse after a predetermined time to permit the
spontaneous ejection of the inflatable system from the stomach.

Fig. 7: Gastro-inflatable drug delivery device

Intragastric osmotically controlled DDS consists of an osmotic pressure-controlled drug

delivery device and aninflatable floating support ina bioerodible capsule, when the device reaches
the stomach, bioerodible capsule quickly disintegrates to release the DDS. The floating support is
made up of a deformable hollow polymeric bag containing a liquid that gasifies at a body
temperature to inflate the bag. The osmotic-pressure controlled drug delivery device consists of
two compartments
 A drug reservoir compartment
 An osmotically active compartment

The drug reservoir compartment is enclosed by a pressure-responsive collapsible bag, which is

impermeable to vapors and liquids and has a drug delivery orifice. The osmotically active
compartment contains an osmotically active salt and is enclosed within a semi-permeable housing.

Fig. 8: Intragastric osmotic controlled

drug delivery system

C. Raft-forming systems
Here, a gel-forming solution (e.g. sodium alginate solution containing carbonates orbi carbonates)
swells and forms a viscous cohesive gel containing entrapped CO2 bubbles (Fig. 9) on contact
with gastric fluid. Formulations also typically contain antacids such as Aluminum hydroxide or
Calcium carbonate to reduce gastric acidity. Because raft-forming systems produce a layer on the
top of gastric fluids, they are often used for gastroesophageal reflux treatment.

Fig. 9: Schematic illustration of the barrier

formed by a raft-forming system
D. Low-density systems
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Gas-generating systems inevitably have a lag time before floating on the stomach contents, during
which the dosage form may undergo premature evacuation through the pyloric sphincter. Low-density
systems (<1 g/cm3) with immediate buoyancy have therefore been developed. They are made of low-
density materials, entrapping oil or air. Most are multiple unit systems, and are also called
‘‘microballoons’’ because of the low-density core.

Table 1: METHODOLOGY
LIST OF MATERIALS AND SUPPLIERS
S.no. Ingredients Supplier
1. Tinidazole Supplied by pharma train
2. Carbopol974p Sdfine chemicals,mumbai
3. Polyethyleneoxide Sdfine chemicals,mumbai
4. Guargum Sdfine chemicals,mumbai
5. Sodiumbicarbonate Sdfine chemicals,Mumbai
6. Citric acid Sdfine chemicals,mumbai
7. Avicelph102(mcc) Fmc biopolymer,mumbai
8. Talc Sdfine chemicals,mumbai
9. Magnesium stearate Sdfine chemicals,mumbai

Table 2: Formulation of Tinidazole floating tablets

by wet granulation method
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Tinidazole 200 200 200 200 200 200 200 200 200
Carbopol 50 75 100 - - - - - -
Polyethylene oxide - - - - - -
50 75 100
Guar gum - - - - - - 50 75 100
Sodium bi carbonate 50 50 50 50 50 50 50 50 50
Citric acid 30 30 30 30 30 30 30 30 30
Pvpk30 30 30 30 30 30 30 30 30 30
Mcc 130 105 80 130 105 80 130 105 80
Talc 5 5 5 5 5 5 5 5 5
Mg.stearate 5 5 5 5 5 5 5 5 5
Total weight 500 500 500 500 500 500 500 500 500

Table 3: LIST OF EQUIPMENT’S

S.no Name of the equipment Model
1 Electronic weighing balance Scale-tec
Roche friabilator electrolab,
2
Friabilator Mumbai
3 Laboratory oven Dtc-00r
4 Compression machine Cmd(cadmach)
5 Tablet hardness tester Pfizerhardnesstester,mumbai
6 Uv Labindiauv3000+
7 Dissolutionapparatus Electrolabtdt-08l
8 Vernier calipers Cd-6”cs
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

RESULTS AND DISCUSSION

Construction of standard calibration curve of tinidazole in 0.1N HCl
The absorbance of the solution was measured at 275nm, using uv spectrometer with 0.1n HCl as blank.
The values are shown in table. A graph of absorbance vs concentration was plotted which indicated in
compliance to beer’s law in the concentration range 5to 25µg/ml

Table 4: Standard calibration graph

values of Tinidazole 0.1N HCl
Concentration
Absorbance
(µg/ml)
0 0
5 0.065
10 0.131
15 0.193
20 0.259
25 0.323

The standard plot of tinidazole plotted by taking absorbance on y–axis and concentration (µg/ml) on x
– axis, the plot is shown figure.

Fig. 10: standard calibration curve of Tinidazole in 0.1nhcl

Inference
The standard calibration curve of tinidazole in 0.1n HCl showed good correlation with regression value
of 0.99%
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Table 5: EVALUATION OF TABLETS

Precompression studies of tinidazole floating tablets
Bulk Tapped
Formulation Hausners Angle
density density Cars index
Code 3 3 ratio of repose(̊)
(kg/cm ) (kg/cm )
F1 0.43 0.52 17.3 1.41 25.62
F2 0.40 0.46 13.0 1.5 31.29
F3 0.50 0.58 13 1.16 29.58
F4 0.44 0.51 13.7 1.25 26.29
F5 0.39 0.47 17.0 1.56 25.23
F6 0.42 0.52 19.2 1.45 25.24
F7 0.36 0.39 7.6 1.0 28.03
F8 0.41 0.50 18 1.5 24.4
F9 0.39 0.48 18 1.23 29.96

Inference
 The tinidazole floting tablets were evaluated for their flow properties; the results for the
blends of compression tablets were shown in table: 5.
 The bulk density and the tapped density for all formulations were found to be almost
similar.
 The carr’s index and hausner’s ratio were found to be in the range of ≤18 and 1.0 to 1.23
respectively, indicating good flow and compressibility of the blends.
 The angle of repose for all the formulations was found to be in the range of 9.92-12.73˚
which indicating passable flow (i.e. Incorporation of glidant will enhance its flow).

Table 6: post compression studies

of tinidazole floating tablets
Formulation %weight Thickness Hardness
%friability %drug content
code variation (mm) (kg/cm2)
F1 Pass 5.06±0.11 0.142 101.3±1.2 5.56±0.057
F2 Pass 5.06±0.15 0.151 102.3±1.7 5.03±0.115
F3 Pass 5.03±0.057 0.62 100.1±1.2 5.01±0.1
F4 Pass 5.1±0.1 0.154 100.7±1.1 5.63±0.05
F5 Pass 5.03±0.05 0.132 99.6±1.5 5.63±0.03
F6 Pass 5.03±0.15 0.143 98.9±2.3 5.5 ±0.05
F7 Pass 4.93±0.05 0.110 100.2±1.7 5.7±0.1
F8 Pass 5.1±0.1 0.133 100.5±1.4 5.53±0.04
F9 Pass 5.02±0.2 0.13 99.2±1.1 5.69±0.05
*test for friability was performed on single batch of 20tablets

Inference
 The variation in weight was within the limit.
 The thickness of tablets was found to be between 4.9-5.2 mm.
 The hardness for different formulations was found to be between 5.01 to 5.69 kg/cm2, indicating
satisfactory mechanical strength.
 The friability was<1.0%w/w for all the formulations, which is an indication of good mechanical
resistance of the tablet.
 The drug content was found to be within limits 98 to 102 %.
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Table 7: Invitro buoyancy studies of

tinidazole floating tablets
Floating Total Matrix
Formulation Lag floating integrity
code Time time upto 12hrs.
(sec) N=3 N=3 N=3
F1 20±0.51 Up to12 +
F2 40±0.21 Up to12 +
F3 80±0.61 Up to12 +
F4 20±0.71 Up to10 -
F5 30±0.81 Up to12 +
F6 35±0.51 Up to12 +
F7 24±0.31 Up to10 -
F8 20±0.81 Up to12 +
F9 36±0.71 Up to12 +

Table 8: concentration of drug

% drug released
Time
F1 F2 F3 F4 F5 F6 F7 F8 F9
(hrs)
0 0 0 0 0 0 0 0 0 0
1 34 27 19 46 39 47 55 43 31
2 49 35 37 67 57 59 67 57 44
4 60 47 45 85 69 71 82 69 57
6 77 61 56 97 87 86 98 82 67
8 89 72 62 100 96 98 100 93 78
10 100 89 77 100 100 100 100 100 86
12 100 100 86 100 100 100 100 100 100
IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Comparative dissolution profile for

F1, F2 and F3 Formulations

%Drug released 120

100

80

60 F1

40 F2
F3
20

0
0 2 4 6 8 10 12 14
Time (Hrs)

Fig. 11: Comparative dissolution profile for f1, f2 and f3 formulation

Comparative dissolution profile for

%Drug released

F4, F5 and F6 Formulations

120

100

80

60 F4

40 F5
F6
20
Time (Hrs)
0
0 2 4 6 8 10 12 14

Fig. 12: Comparative dissolution profile for f4, f5 and f6 formulations

IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Comparative dissolution profile for

F7, F8 and F9 Formulations

120
%Drug released

100

80

60 F7

40 F8`
F9
20

0
0 2 4 6 8 10 12 14

Time (Hrs)

Fig. 13: Comparative dissolution profile for f7, f8 and f9 formulations

Table 9: r2value and n result table

Formulation R2 value
“n” value
code Zero order First order Higuchi Peppas
F2 0.962 0.795 0.982 0.978 0.527

Zero order plot for best formulation F2

120
y=7.4725x+13.711
%Drug released

100 R² =0.9622

80

60
F2
40 Linear(F2)

20

0
0 2 4 6 8 10 12 14

Time (Hrs)

Fig. 14: Zero order plot for best formulation f2

IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Fig. 15: First order plot for best formulation f2

Fig. 16: Higuchi plot for best formulation f2

IJRPC 2022, 12(2), 164-177 Jagan Mohan Reddy et al ISSN: 22312781

Peppas plot for best formulation F2

2.5

Log% Drug released y=0.5276x+1.397

2 R² =0.9788

1.5

F2
1
Linear(F2)
0.5

0
0 0.2 0.4 0.6 0.8 1 1.2
Log time

Fig. 17: Peppas plot for best formulation f2

 Among the different control release polymers, carbopol was showing highest drug release
retarding capacity
 F2 was showing the satisfactory results.
 F or f2 formulation diffusion exponent n value is in between 0.45 to 0.89 so they are following
non ficki ananmolous diffusion model

SUMMARY AND CONCLUSION

From the experimental data, it can be concluded that
 Floating tablets of tinidazole are formulated to increase gastric residence time and there by
improve its therapeutic efficacy.
 Carbopol was respectively showed better sustained drug release of tinidazole.
 Synthetic polymers were showing more rate retarding drug release and matrix integrity.
 When drug : polymer concentration increases the release rate decreases this is because of
reason when the concentration of polymer increases the diffusion path length increases
 Formulated tablets showed satisfactory results for various post compression evaluation
parameters like: tablet thickness, hardness, weight variation, floating lag time, total floating
time, content uniformity and invitro drug release.
 Formulation f2 gave better-controlled drug release and floating properties in comparison to
the other formulations.
 The release pattern of the f2 formulations was best fitted to korsmeyer-peppas model, higuchi
and first-order model.
 The most probable mechanism for the drug release pattern from the formulation was non-
fickian diffusion or anomalous diffusion.

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