2. review of literature 2.1. literature reviewed on...
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33 Chapter 2 Review of Literature
2. REVIEW OF LITERATURE
Past works reported on the FDDS includes floating tablets, floating capsules,
balloon tablets, multi-particulate systems, hollow micro spheres, floating beads,
polymers used for FDDS and production of chitosan etc. Few available reports were
briefly reviewed.
2.1. Literature reviewed on floating drug delivery systems
2.1.1. Floating tablets and capsules
Streubel et al., 63
have reported floating matrix tablets based on low density
foam powder and the effects of formulation and processing parameters on drug
release. The effect of polypropylene foam powder on the in vitro floating behavior
was found to be excellent. The effect of HPMC, polyacrylates, sodium alginate, corn
starch, carageenan, guar gum and gum Arabic on the drug release was studied. It has
been concluded that the release rate of drug could effectively be modified by varying
the matrix forming polymer/foam blends and the addition of water soluble or water
insoluble filters such as lactose or micro crystalline cellulose.
Shoufeng Li et al., 64
have reported effect of HPMC and carbopol on the
release and floating properties of gastric floating drug delivery system using factorial
design. The difference in the drug release and the floating properties of GFDDS could
be attributed to the difference in basic properties of three polymers, HPMC, K4M,
K100 and carbopol 934, due to their water uptake potential and functional group
substitution was reported.
Nurten Ozdemir et al., 65
reported Floating dosage forms of furosemide by in
vitro and in vivo evaluations, because of the lower solubility of drug in the gastric
medium, it was first enhanced by preparing an inclusion complex of furosemide with
34 Chapter 2 Review of Literature
beta-cyclodextrin (β-CD) in a 1:1 proportion using the kneading method. A
considerable significant correlation was reported between in vivo results and in vitro
data of their dissolution rate.
Sheth et al., 66
have reported gastric retentive characteristics of
hydrodynamically balanced systems of diazepam and chlordiazepoxide as well as the
blood level profile for both drugs, the hydrodynamically balanced systems was
retained in the stomach for a longer period of time than conventional tablets
swallowed concurrently, and slowed gastric retention time up to 6 hours.
Ingani et al., 67
have reported conception and in vivo investigation of peroral
sustained release floating dosage forms with enhanced gastro intestinal transit of
sodium riboflavin 5'-phosphate. They formulated double layered sustained release
tablets of sodium riboflavin 5'-phosphate without gas generating agent, and sustained
release floating tablet and sustained release floating capsules with Methocel K4M,
K15M and gas generating agents sodium bicarbonate and citric acid.
Agyilirah et al., 68
evaluated the gastric retention properties of a cross-linked
polymer coated tablet versus those of a non-disintegrating tablet in both fasted and fed
conditions with human volunteers using gamma camera scintigraphy. The emptying
time for both coated and uncoated tablets were much shorter in the fasting state and
the balloon tablet did not significantly prolong the gastric emptying time in fasted
state.
Hilton et al., 69
reported in vitro and in vivo evaluation of an oral sustained
release floating dosage form of amoxycillin trihydrate. Various hydrophilic polymers
were investigated, the most suitable system contained a 1:2 ratio of hydroxy propyl
35 Chapter 2 Review of Literature
cellulose to drug compressed easily and was not affected by alteration in normal
compaction pressure.
Sanford Bolton et al., 70
formulated novel floating controlled release drug
delivery system using a mineral oil and agar and radiolabeled floating tablets were
prepared by adding radiolabeled indium III with the same constituents and only the
radiolabeled tablets were dip coated to retain the marker within the tablet and the in
vitro- in vivo release rate were compared with Theo-dur (Key Pharma).
Anil Menon et al., 71
have developed monolithic floating dosage form of
furosemide using different grades of HPMC K100, K4000 and K15000. A two factor
three level full factorial experimental design was employed for formulation
development.
Timmermans et al., 72
have studied factors controlling the buoyancy and
gastric retention capabilities of floating matrix capsules.
Libo Yang et al., 73
studied zero-order release kinetics from a self-correcting
floatable asymmetric configuration drug delivery system. The approach was based on
the three-layer matrix technology to control drug release for oral administration.
Polyethylene oxide polymers of various molecular weights together with theophylline
as drug model and other excipients have been directly compressed into a three-layer
asymmetrical floatable system.
Deshpande A.A et al., 74
developed a novel controlled release gastric retention
tablets containing soluble drug chlorpheniramine maleate and a poorly soluble drug
riboflavin 5' phosphate using Carbopol 934P as a gelling agent, these tablets were
coated with a permeable and elastic polymer Eudragit RL30D and NE30D was used
to provide an initial alkaline micro-environment and confer buoyancy to tablet.
36 Chapter 2 Review of Literature
Gan Lin Chen et al., 75
have formulated floating sustained release capsules of
verapamil using hydroxy propyl cellulose-M and HPMC and HPMC K15M. The
effect of weight filled in the capsules, amount of HPMC, addition of effervescent on
the dissolution kinetics were studied. The conventional capsules were filled with
verpamil, HPC and effervescent. The release of verapamil from the capsules followed
the Higuchi release model. However, when effervescent was added, a zero -order drug
release was observed after a burst phase, entrapped air was considered as a barrier to
diffusion and matrix relaxation in drug release.
Ina Krogel et al., 76
reported floating and pulsatile drug delivery system of
chlorpheniramine maleate based on reservoir system consisting of a drug containing
effervescent core and a polymeric coating. The mechanical properties (puncture
strength and elongation) of acrylic (Eudragit RS, RL or NE) and cellulosic (cellulose
acetate, ethyl cellulose) polymers, which primarily determined the type of delivery
system, were characterized with a puncture test in the dry and wet state. The drug
release was more retarded with the HPMC two-layer tablets, which floated within
minutes. Increasing the HPMC concentration decreased the drug release were
reported from their study.
Zhenping Wei et al., 77
have designed and evaluated a two layer floating tablet
for gastric retention using cisapride as a model drug. The in vitro drug release was
determined and the resulting buoyancy and the time buoyancy curves were plotted.
Their study concluded that the two distinct layers allow separate regulation of the
floating ability and drug release kinetics.
Rosa et al., 78
have reported design and testing In vitro of a bioadhesive and
floating drug delivery system of sotalol HCl for oral application using sodium CMC,
HPC and sodium bicarbonate gas generating agent were investigated.
37 Chapter 2 Review of Literature
2.1.2. Non effervescent FDDS
Franz M R et al., 79
described a bi-layer buoyant dosage form consisting one as
drug release layer misoprostol and other was buoyant floating layer. Each layer
included a hydrocolloidal gelling agent such as hydroxy propyl methylcellulose
(HPMC), gums, polysaccharides and gelatin.
Dennis et al., 80
invented a buoyant controlled release pharmaceutical powder
formulation filled into capsules which releases the drug of a basic character at a
controlled rate regardless of the pH of the environment.
Mitra et al., 81
developed a sustained release multilayered, flexible sheet-like
medicament device. The drug was dispersed or dissolved in this layer and a barrier
film overlaid the carrier film.
Thanoo et al., 82
had developed polycarbonate microspheres by solvent
evaporation technique. Polycarbonate in dichloromethane was found to give hollow
microspheres that floated on water and simulated biofluids as evidenced by scanning
electron microscopy (SEM). They stated that high drug loading was achieved and
drug-loaded microspheres were able to float on gastric and intestinal fluids and it was
found that increasing the drug-to-polymer ratio increased both their mean particle size
and release rate of drug.
2.1.3. Effervescent FDDS
Ichikawa et al., 83
described capsules, which is composed of a plurality of
granules that have different residence times in the stomach and consist of an inner
foamable layer of gas-generating agents and outer layer containing organic acid. This
layer was further divided into two sub layers. Inner foamable layer this layer was
surrounded by an expansive polymeric film which allowed gastric juice to pass
38 Chapter 2 Review of Literature
through, and was found to swell by foam produced by the action between the gastric
juices and the gas-generating agents.
Atyabi et al., 84
developed a floating system using ion exchange resin that was
loaded with bicarbonate by mixing the beads with 1M sodium bicarbonate solution.
The in vivo behavior of the coated and uncoated beads was monitored using a single
channel analyzing study in 12 healthy human volunteers by gamma radio
scintigraphy.
2.1.4. Multiple Units
Ichikawa et al., 85
developed a new multiple type of floating dosage system
composed of effervescent layers and swellable membrane layers coated on sustained
release pills. They finally proposed a system with good floating ability independent of
pH and viscosity and the release of drug (Para-amino benzoic acid) in a sustained
manner.
Whitehead et al., 86
have developed freeze dried calcium alginate multiple unit
floating dosage forms, which demonstrated favorable in vitro floating characteristics
and the in vivo behavior of this system was compared to a multiple unit non floating
dosage form manufactured from identical material which was carried out in human
volunteers.
Iannuccelli et al., 87
have reported air compartment multiple-unit system for
prolonged gastric residence. They conducted in vivo buoyancy in three different
sessions (fasted state, fed state after a meal and fed state after a succession of meal)
by administering to each subject at the same time both floating and control release
systems loaded with barium sulphate.
2.1.5. Hollow Microspheres and Micro Particles
39 Chapter 2 Review of Literature
Kawashima et al., 88
have reported hollow microspheres of tranilarts and
ibuprofen with Eudragits for the use of floating controlled drug delivery system in the
stomach. The drug release behavior of the micro balloons was characterized as an
enteric property and the drug release rates were drastically reduced depending on the
polymer concentration at pH 6.8.
El Kamel et al., 89
prepared sustained release ketoprofen floating micro
particles by the emulsion-solvent diffusion technique using four different ratios of
Eudragit S100 with Eudragit RL were used to form the floating microparticles. It was
observed from their report that the drug retained in the floating micro particles
decrease with increase in Eudragit RL coated microparticles.
2.1.6. Floating Beads
Nakamachi et al., 90
reported floating dosage form of Nicardipine
hydrochloride and hydroxyl propyl methyl cellulose acetate succinate, prepared by
using a twin screw extruder. By adjusting the position of the high pressure screw
elements in the immediate vicinity of die outlet and by controlling the barrel
temperature, they were able to prepare a puffed dosage form with very small and
uniform pores. They concluded that puffed dosage forms of hydroxyl propyl methyl
cellulose acetate succinate prepared using twin screw extruder was useful for
achieving a long intragastric retention.
Bulgarelli et al., 91
studied the effect of matrix composition and process
conditions on casein gelatin beads prepared by emulsification extraction method. It
was observed that the percentage of casein in matrix increases the drug loading of
both low and high porous matrices, although the loading efficiency of high porous
matrices is lower than that of low porous matrices.
40 Chapter 2 Review of Literature
Whitehead et al., 92
have studied amoxycillin release from floating beads
prepared from alginate solutions containing either dissolved or suspended
amoxycillin. The beads were produced by the drop wise addition of the alginates into
calcium chloride solution, followed by removal of the gel beads and freeze-drying.
Sustained release characteristics of the beads were increased by the addition of
amylose.
Yasunori Sato et al., 93
reported pharmaco-scintigraphic evaluation of
riboflavin containing microballoons for a floating controlled drug delivery system in
healthy humans. Simultaneously pharmacokinetic examination of riboflavin released
from micro balloon and non floating micro spheres were conducted in fasted and fed
human subjects. Pharmacokinetic parameters, e.g., excretion, half-life time and total
urinary excretion were well correlated with GRT determined by the gamma
scintography analysis.
2.1.7. Other types of FDDS
Timmermans et al., 94
studied the effect of size of floating and non floating
dosage forms on gastric emptying and concluded that the floating units remained
buoyant on gastric fluids. These are less likely to be expelled from the stomach
compared with the non-floating units, which lie in the antrum region and are propelled
by the peristaltic waves.
Choi et al., 95
prepared 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. Their 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
41 Chapter 2 Review of Literature
floating beads. 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%).
Li et al., 96
evaluated the contribution of formulation variables on the floating
properties of a gastro floating drug delivery system using a continuous floating
monitoring device and statistical experimental design. Analysis of variance (ANOVA)
test on the results from these experimental designs demonstrated that the hydrophobic
agent magnesium stearate could significantly improve the floating capacity of the
delivery system. Better floating was achieved at a higher HPMC/carbopol ratio and
this result demonstrated that carbopol has a negative effect on the floating behavior.
Penners et al., 97
developed an expandable tablet containing mixture of
polyvinyl lactams and polyacrylates that swell rapidly in an aqueous environment and
thus reside in stomach over an extended period of time. In addition to this, gas-
forming agents were incorporated. As the gas formed, the density of the system was
reduced and thus the system tended to float on the gastric contents.
Fassihi et al., 98
developed a zero-order controlled release multilayer tablet
composed of at least 2 barrier layers and 1 drug layer. All the layers were made of
swellable, erodible polymers and the tablet was found to swell on contact with
aqueous medium.
Talwar et al., 99
developed a once-daily formulation for oral administration of
ciprofloxacin composed of 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03%
xanthum gum, 13.7% sodium bicarbonate, and 12.1% cross-linked poly vinyl
pyrrolidine. The hydrated gel matrix created a tortuous diffusion path for the drug,
resulting in sustained release of the drug.
42 Chapter 2 Review of Literature
Baumgartner et al., 100
developed a matrix-floating tablet containing 54.7% of
drug, HPMC K4 M, Avicel PH 101, and a gas-generating agent They compared the
gastric motility and stomach emptying between humans and dogs which showed no
big difference and therefore they speculated that the experimentally proven increased
gastric residence time in beagle dogs could be compared with known literature for
humans.
Nur et al., 101
had developed floating tablets of captopril using HPMC (4,000
and 15,000 cps) and carbopol 934P. It was concluded that the buoyancy of the tablet
is governed by both the swelling of the hydrocolloid particles on the tablet surface
when it contacts the gastric fluids and the presence of internal voids in the center of
the tablet (porosity). A prolonged release from these floating tablets was observed as
compared with the conventional tablets and a 24-hour controlled release from the
dosage form of captopril was achieved.
Asmussen et al., 102
invented a device for the controlled release of active
compounds in the gastrointestinal tract with delayed pyloric passage, which expanded
in contact with gastric fluids and the active agent was released from a multiparticulate
preparation. It was claimed that the release of the active compound was better
controlled when compared with conventional dosage forms with delayed pyloric
passage.
Illum et al., 103
develop a microsphere that released the active agent in the
stomach environment over a prolonged period of time. The microspheres were
prepared by spray drying an oil/water or water/oil emulsion of the active agent, the
water-insoluble polymer and the cationic polymer.
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Ushomaru et al., 104
did their work on preparing a sustained release
composition for a capsule containing mixture of cellulose derivative or a starch
derivative that formed a gel in water and higher fatty acid glyceride and/or higher
alcohol.
S Bolton et al., 105
carried their research on a non compressed sustained release
tablet that remained afloat on gastric fluids. The tablet formulation comprised 75% of
drug and 2% to 6.5% of gelling agent and water. The non compressed tablet had a
density of less than 1 and sufficient mechanical stability for production and handling.
Spickett et al., 106
invented an antacid preparation having a prolonged gastric
residence time containing a internal phase of a solid antacid and the external phase
consisted of hydrophobic organic compounds (mono-, di-, and triglycerides) for
floating and a non-ionic emulsifier.
Wu et al., 107
developed floating sustained release tablets of nimodipine by
using HPMC and PEG 6000. Prior to formulation of floating tablets, nimodipine was
incorporated into poloxamer-188 solid dispersion after which it was directly
compressed into floating tablets. It was observed that by increasing the HPMC and
decreasing the PEG 6000 content a decline in vitro release of nimodipine occurred.
Dave et al., 108
developed a gastro retentive drug delivery system of ranitidine
hydrochloride was designed using guar gum, xanthan gum, and hydroxy propyl
methyl cellulose. Sodium bicarbonate was incorporated as a gas-generating agent. The
effect of citric acid and stearic acid on drug release profile and floating properties was
investigated. A 32 full factorial design was applied to systemically optimize the drug
release profile and the results showed that a low amount of citric acid and a high
44 Chapter 2 Review of Literature
amount of stearic acid favor sustained release of ranitidine hydrochloride from a
gastro retentive formulation.
Reddy et al., 109
have discussed advantages and various disadvantages of
single-and multiple-unit hydrodynamic systems. They also reviewed clearly about the
overcoming of various limitations and the mechanism involved in floatation.
Mahesh Chavanpatil et al., 110
reported that psyllium husk with HPMC K100M
increases the dimensional stability of the formulations, which is necessary in case of
once daily formulations. Cross povidone has improved the drug release profile and
swelling factor of psyllium husk based formulations, they also concluded that
channeling agents, such as beta cyclodextrin are useful to increase the initial burst
release from psyllium husk based formulations. The optimized formulation was found
to be stable at all the stability conditions. Based on the in vivo performance in a
parallel study design in healthy subjects, the developed formulation shows promise to
be bioequivalent to the marketed product of ofloxacin (Zanocin).
Wong et al., 111
developed a prolonged release dosage form adapted for gastric
retention using swellable polymers. It consisted of a band of insoluble material that
prevented the covered portion of the polymer matrix from swelling and provided a
segment of a dosage form that was of sufficient rigidity to withstand the contractions
of the stomach and delayed the expulsion of the dosage form from the stomach.
2.2. Literature reviewed on anti ulcer drugs
Brijesh et al., 112
had prepared a gastro retentive drug delivery system of
ranitidine hydrochloride. The effects of citric acid and Stearic acid on drug release
profile and floating properties were investigated. These studies indicate that the
45 Chapter 2 Review of Literature
proper balance between a release rate enhancer and a release rate retardant can
produce a drug dissolution profile similar to a theoretical dissolution profile.
Dumpeti Janardhan et al., 113
had prepared a gastro retentive drug delivery
system of ranitidine hydrochloride by direct compression using different
concentrations of Hydroxy Propyl methyl cellulose (HPMC K4M), Carbopol, Sodium
Carboxy methyl cellulose, sodium bicarbonate and citric acid. The statistical analysis
of the parameters dissolution efficiency of dissolution data, floating behavior and drug
content after storage at 40°C and 75% relative humidity for three months were studied
by showed by Student’s t-test which indicates no significant and provide a minimum
shelf life of 2 years.
Alagu sundaram et al., 114
highlights the formulation and evaluation of
mucoadhesive buccal films of Ranitidine HCl. The best mucoadhesive performance
and matrix controlled release was exhibited by the formulation (2 % HPMC and 1 %
PVP) which is confirmed by the kinetic data of drug release.
Dinesh Dhamecha et al., 115
had formulated floating drug delivery systems
with an objective to sustain the release of Ranitidine hydrochloride in stomach and
evaluated for In vitro buoyancy, floating time and in-vitro drug release studies.
Hitesh Chavda, Chaganbhai Patel116
have developed a drug delivery system
based on a superporous hydrogel composite for floating and sustained delivery of
Ranitidine hydrochloride. They evaluated release profile by changing the release
retardant polymer in the formulation. They concluded that the floating delivery
system based on the superporous hydrogel containing chitosan as a composite
material, was promising for stomach specific delivery of Ranitidine hydrochloride.
46 Chapter 2 Review of Literature
Jaimini et al., 117
investigated gastro retentive drug delivery system of
famotidine employing two different grades of methocel K100 and methocel K15M by
effervescent technique, these grades of methocel were evaluated for their gel forming
properties.
2.3. Literature reviewed on polymers used for FDDS
Monica et al., 118
has formulated and optimized an effervescent floating tablet
formulation of salbutamol sulfate using combination of two viscosity grades of
polymers HPMC K4M and HPMC K 100M. The effect of polymer in release rate and
other parameters were studied in detail by using full factorial design.
Sauzet et al., 119
developed floating gastro retentive dosage form (GRDF)
using a low-density dosage form containing high active pharmaceutical ingredient
(API) concentration by using a hydrophobic dusty powder excipient under specific
conditions by adopting art wet granulation manufacturing process. The GRDF was
characterized for apparent density, buoyancy, porosity and dissolution using in vitro
experimentations.
Ajit Kulkarni et al., 120
had their research in developing a bilayer
regioselective floating tablets of atenolol and lovastatin to give immediate release of
lovastatin and sustained release of atenolol. They have undergone direct compression
method for formulation of the bilayer tablets. From the various evaluation and
stability studies they concluded that the biphasic drug release pattern was successfully
achieved through the formulation of floating bilayer tablets.
Ramesh bomma et al., 121
developed floating matrix tablets of norfloxacin by
the wet granulation technique using polymers such as hydroxypropyl methylcellulose
(HPMC K4M, HPMC K100M) and xanthan gum. They concluded from their research
47 Chapter 2 Review of Literature
that the tablets remained in the stomach for 180 ± 30 min in fasting human volunteers
and indicated that gastric retention time was increased by the floating principle, which
was considered desirable for the absorption window drugs.
Rajeev Garg et al., 122
had their research in preparing floating tablets of
Silymarin as model drug by various materials like hydroxyl propyl methylcellulose
(HPMC) K 4M, K15M, Psyllium husk, swelling agent as cross povidone and
microcrystalline cellulose and gas generating agent like sodium bicarbonate and citric
acid and evaluated for floating properties, swelling characteristics and in vitro drug
release studies.
Ferdous Khan et al., 123
has investigated the release mechanisms and explained
with zero order, first order, Higuchi, Korsmeyer and Hixon-Crowell equations. Their
work states that the release rate, extent and mechanisms were found to be governed by
the content of polymer and floating agent. Kinetic modeling of dissolution profiles
revealed that the drug release mechanism could range from diffusion controlled to
case II transport, which was mainly dependent on presence of relative amount of
theophylline, polymer and floating agent.
Shailesh et al., 124
developed an optimized gastric floating drug delivery
system (GFDDS) containing domperidone with three polymers: hydroxypropyl
methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate
(X3), as independent variables by Box-Behnken design was employed in formulating
the GFDDS.
Goole et al., 125
attempted to develop a new coated multiple unit sustained
release floating system that is able to float over an extended period of time. Levodopa
was used as a model drug. The system consisted of a 3 mm drug containing gas
48 Chapter 2 Review of Literature
generating core, prepared by melt granulation and subsequent compression, and
coated with a flexible polymeric membrane. Eudragit RL30 D and ATEC were used
as a film former and a plasticizer, respectively.
Patel et al., 126
developed floating tablets using melt granulation technique.
Bees wax was used as a hydrophobic meltable material. Hydroxy propyl methyl
cellulose, sodium bicarbonate and ethyl cellulose were used as matrixing agent, gas-
generating agent and floating enhancer, respectively. The tablets were evaluated for in
vitro buoyancy and dissolution studies. Formulation developed using simplex lattice
design were fitted to various kinetic models for drug release. Their investigation
demonstrates the use of simplex lattice design in the development of floating tablets
with minimum experimentation.
Girish et al., 127
developed a bilayer and floating-bioadhesive drug delivery
system exhibiting a unique combination of floatation and bioadhesion to prolong
residence in the stomach using rosiglitazone maleate as a model drug. The release of
rosiglitazone maleate from the tablets followed the matrix first-order release model.
The concentration of HPMC significantly affects the drug release rate, buoyancy lag-
time, detachment force and swelling characteristics of the tablets. This kind of tablet
exhibits independent regulation of buoyancy and drug release.
Sunil et al., 128
developed a floating granular delivery consisting of calcium
silicate as porous carrier, repaglinide and carbopol 940 as matrix forming polymers
was prepared and evaluated formulation and process variables on the particle
morphology, micrometric properties, in-vitro floating behavior, drug content (%) and
in-vitro drug release was studied.
49 Chapter 2 Review of Literature
Manoj et al., 129
had worked on floating drug delivery system of diltiazem
hydrochloride (DTZ) using polymers such as hydroxyl propyl methyl cellulose
(HPMC, Methocel K100M CR), Compritol 888 ATO, alone and in combination by
direct compression technique.
Ziyaur Rahman et al., 130
carried a research in preparing a bilayer floating
tablet for captopril using direct compression technology. They have administered a
placebo formulation containing barium sulphate in the release layer to human
volunteers for in vivo X-ray studies.
Jalesh Varshosaz et al., 131
prepared floating-bioadhesive tablets to lengthen
the stay of drug in its absorption area. Form their studies they concluded that tablets
with 5% effervescent base had longer lag time than 10% and all the formulations
showed a Higuchi, non-Fickian release mechanism.
Xiaoqiang Xu et al., 132
developed a sustained release tablet for
phenoporlamine hydrochloride because of its short biological half-life. Three floating
matrix formulations of phenoporlamine hydrochloride based on gas forming agent
were prepared.
Ravindra Dhumal et al., 133
designed a gastro retentive delivery system for
bimodal of cefuroxime axetil. Bilayer tablet, each layer containing dose of drug was
formulated with one immediate release layer and another floating matrix layer. Thus,
bimodal drug release comprising of immediate release for quick onset of action
followed by controlled release minimizing the concentration of unabsorbed drug
entering colon was achieved from their research. No change in amorphous nature of
drug during processing was observed, which was confirmed by differential scanning
50 Chapter 2 Review of Literature
colorimeter and X-ray diffractometer. The γ – scintigraphy confirmed the gastric
residence of tablets in human volunteers.
Narendra et al., 134
developed an optimized gastric floating drug delivery
system containing metoprolol tartrate as a model drug by the optimization technique.
A 23 factorial design was employed in formulating with four dependent variables. The
main effect and interaction terms were quantitatively evaluated using a mathematical
model. The best formulation was identified by regression analysis and numerical
optimization.
Wieslaw Sawicki et al., 135
developed method of compression of floating
pellets with verapamil hydrochloride. Compression of pellets into tablets, being a
modern technological process, is much more perfect than enclosing them in a hard
gelatin capsule. They examined using three plasticizers namely propylene glycol,
triethyl citrate and dibuthyl sebecate (all at concentration of 10%). Pellets were
prepared by wet granulation of powder mixture, spheronization of the granulated mass
and coating of the cores with a sustained release film. Tablet cross-section
photographs were taken confirming necessary coating film thickness preventing their
deformation caused by compressing into tablets.
Streubel et al., 136
developed and physicochemically characterized the single
unit, floating controlled drug delivery systems consisting of polypropylene foam
powder, matrix-forming polymer(s), drug, and filler. The release rate could effectively
be modified by varying the ‘‘matrix-forming polymer/foam powder’’ ratio, the initial
drug loading, the tablet geometry (radius and height), the type of matrix-forming
polymer, the use of polymer blends and the addition of water-soluble or water-
insoluble fillers (such as lactose or microcrystalline cellulose).
51 Chapter 2 Review of Literature
Nurten Ozdemir et al., 137
designed to enhance the bioavailability of
furosemide with beta-cyclodextrin (β-CD) in a 1:1 proportion, a floating dosage form
with controlled release by kneading method. A considerably significant correlation
was detected between in vivo results and in vitro data of the dissolution rate, and they
concluded that the modified continuous flow - through cell method is usable for in
vitro dissolution rate tests of floating dosage forms.
Nathalie Rouge et al., 138
evaluated the possible advantages of floating and
high density dosage forms and their influence on pharmacokinetic parameters. They
prepared three formulations containing 25 mg atenolol, a floating multiple-unit
capsule, a high density multiple unit capsule and an immediate release tablet were
compared with respect to estimated pharmacokinetic parameters.
2.4. Literature reviewed on production of chitosan and used as polymer for
FDDS
L.A.A. Pinto et al., 139
have optimized deacetylation in the production of
chitosan from shrimp wastes by using response surface methodology for the
polymer’s molecular weight. The optimum condition for the deacetylation reaction for
molecular weight was observed at a temperature of 130°C and in 90min and
corresponded to a moleculare weight of chitosan of about 150KDa and a deacetylation
degree of 90%.
Harpreet K. Dhiman et al., 140
have prepared biodegradable polymer scaffolds
from chitosan with varying degree of deacetylation for in vitro culture of human
breast cancer MCF-7 cell lines. These polymers were characterized in terms of
functional groups by FTIR and swelling properties. Polymers having high degree of
deacetylation showed better swelling properties irrespective of molecular weight.
52 Chapter 2 Review of Literature
They proved that this polymer was biocompatible and non-toxic towards human
epithelial cells.
Marguerite Rinaudo141
has reviewed papers on the high value-added
applications of chitosan used in medicine and cosmetics. Who described about
chitosan, which is soluble in acidic aqueous media, is used for many applications such
as food, cosmetics, biomedical and pharmaceutical fields.
V.R. Sinha et al., 142
have reviewed and described about the factors that affect
the entrapment efficiency and release kinetics of drugs from chitosan microspheres. It
has been shown that chitosan is a biodegradable natural polymer with great potential
for pharmaceutical application due to its biocompatibility, non-toxicity and gel
formation.
Mansoor Amiji and Radi Hejazi143
have reviewed chitosan based
gastrointestinal delivery system. They summarized the recent applications of chitosan
in oral and stomach specific drug delivery system. They found chitosan as a
promising material for GI drug delivery applications as many formulations are being
examined.
Katharina M. Picker-Freyer and Diana Brink144
have evaluated the powder and
tableting properties of chitosan. They analyzed the process of tablet formation and the
properties of the resulting tablets for 3 N-deacetylated chitosan, with a degree of
deacetylation of 80%, 85% or 90%. They were studied material properties such as
water content, particle size and morphology, glass transition temperature and
molecular weight.
Maher Z. Elsabee et al., 145
have extracted chitosan from different local
sources in Egypt. The obtained chitin was converted into the more soluble chitosan by
53 Chapter 2 Review of Literature
steeping into solutions of NaOH of various concentrations and for extended period of
time. The obtained chitosan was characterized by special analysis, x-ray diffraction
and thermogravimetric analysis.
Alaa Eldeen B. Yassin et al., 146
have designed a new extended release
gastroretentive multiparticulate delivery system for verapamil by incorporation into
hydrogel beads made of chitosan. Beads prepared using medium molecular weight
chitosan showed both the slowest release rate, good floating characteristics
comprising short onset and the long duration of buoyancy.
2.5. Conclusion
Controlled release floating drug delivery systems enable prolonged and
continuous output of the drug to the upper parts of the gastro intestinal tract and
improve the bioavailability of medications that are characterized by a narrow
absorption window.
From the review of literature it could be understood that FDDS provides a
means to utilize all the pharmacokinetic (PK) and pharmacodynamic (PD) advantage
of controlled release dosage forms for antiulcer.
Based on the literature surveyed, it may be conclude that drug absorption in
the gastro intestinal tract is a highly variable process and prolonged gastric retention
of the dosage form extends the time for drug absorption. Due to complexity of
pharmacokinetic and pharmacodynamic parameters, further studies are required to
establish the optimal dosage form for a specific H2 receptor antagonist drugs.
For certain drugs interplay of its pharmacokinetic and pharmacodynamic
parameters will determine the effectiveness and benefits of the FDDS as compared to
the other dosage forms.