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Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 18
2. REVIEW OF LITERATURE:
2.1 Research Work Review:
Patel, et al., (2009), developed a gastro retentive controlled release drug delivery
system of verapamil HCl using Hydroxypropylmethylcellulose (HPMC), carbopol,
and xanthan gum (gel-forming properties) and sodium bicarbonate and anhydrous
citric acid (Buoyancy). It was concluded that the optimized intragastric floating tablet
composed of 3:2 of HPMC K4M to xanthan gum exhibited 95.39% drug release in 24
h in vitro, while the buoyancy lag time was 36.2 s, and the intragastric floating tablet
remained buoyant for >24 h. Zero-order and non-Fickian release transport was
confirmed as the drug release mechanism from the optimized formulation. X-ray
studies showed that total buoyancy time was able to delay the gastric emptying of
verapamil HCl intragastric floating tablet in mongrel dogs for more than 4 h56.
Rao, et al., (2009) the purpose of this research was to formulate and optimize an
effervescent floating tablet formulation of Salbutamol sulfate using full factorial
design. Salbutamol sulfate has an absorption window in the stomach and in the upper
part of the small intestine. A 32 full factorial design was utilized to optimize the
formulation wherein the content of hydroxylpropyl methyl cellulose (HPMC) (X1)
and sodium bicarbonate (X2) were taken as independent variables and % drug release
after 6 h (Y1), t50% (Y2 ), and buoyancy lag time (BLT) (Y3) were taken as the
dependent variables. Salbutamol sulfate, HPMC K4M and HPMC K100M CR, stearic
acid, talc, dicalcium phosphate, polyvinyl pyrrolidone, and magnesium stearate were
used for the current research work. Two viscosity grades of HPMC as matrix
materials were used for formulating the tablets, which were prepared by wet
granulation.
Prajapati, et al., (2009) floating matrix tablets of domperidone were developed to
prolong gastric residence time and thereby increased drug bioavailability.
Domperidone was chosen as a model drug because it is poorly absorbed from the
lower gastrointestinal tract. The tablets were prepared by wet granulation technique,
using polymers such as hydroxyprobylmethylcellulose K4M, carbopol 934P, and
sodium alginate, either alone or in combination, and other standard excipients. Tablets
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 19
were evaluated for physical characteristic viz. hardness, % friability, floating capacity,
weight variation and content uniformity.
Arza, et al., (2009), developed swellable, floating, and sustained release tablets by
using a combination of hydrophilic polymer (hydroxypropyl methylcellulose),
swelling agents (crospovidone, sodium starch glycolate, and croscarmelose sodium)
and effervescent substance (sodium bicarbonate). The drug release of optimized
formulation follows the Higuchi kinetic model, and the mechanism was found to be
non-Fickian/anomalous according to Korsmeyer-Peppas (n value is 0.68). In vivo
nature of the tablet at different time intervals was observed in the radiographic
pictures of the healthy volunteers and MRT in the stomach was found to be 320+/-
48.99 min (n=6). A combination of HPMC K100M, crospovidone, and sodium
carbonate shows the good swelling, drug release, and floating characters than the
CIFRAN OD57.
Martinez, et al., (2008), developed a sustained release floating matrix tablets of
captopril from metolose SH 4000 SR/sodium bicarbonate and studied the effect of
varying proportion of metolose and sodium bicarbonate at two different compaction
pressure. It was concluded that tablets matrices compacted at 55MPa float in the
dissolution medium for more than 8 h. Tablets compacted at 165MPa were found to
be float only when sodium bicarbonate was included in the formulation. The matrix
density was lower when compacted at 55MPa. The drug released with time was lesser
when sodium bicarbonate is included in the formulation because the carbon dioxide
bubbles obstruct the diffusion path and decrease the matrix coherence58.
Strubing, et al., (2008), developed a floating tablets of Propranolol HCl with
Kollidon SR as an excipient for direct compression and different Kollicoat SR 30
D/Kollicoat IR coats varying from 10 to 20 mg polymer/cm2 and investigated
regarding drug release in 0.1 N HCl. Coated tablets with 10 mg polymer/cm2 SR/IR,
8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset,
the fastest increase in and highest maximum values of floating strength. The drug
release was delayed efficiently within a time interval of 24 h by showing linear drug
release characteristics. Poly (vinyl acetate) proved to be appropriate excipients to
ensure safe and reliable drug release59.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 20
Reddy, et al., (2008) Delayed release microspheres of aceclofenac were formulated
using an enteric polymer, cellulose acetate phthalate (CAP) prepared by solvent
evaporation technique. The effects of various other modern enteric polymers such as
hydroxyl propyl methyl cellulose phthalate (HPMCP), Eudragit L100 on the release
of aceclofenac from the CAP microshperes have been evaluated.
Gattani, et al., (2008) was evaluated formulation and evaluation of intragastric
floating drug delivery system of diltiazem hydrochloride the present study is aimed
towards formulation and evaluation of floating multiparticulate oral drug delivery
system of diltiazem hydrochloride, which can provide sustained release using ethyl
cellulose and Eudragit RS-100 as the controlling polymer.
Jang, et al., (2008), developed a gastroretentive drug delivery system of DA-6034, a
new synthetic flavonoid derivative of Eupatilin, for the treatment of gastritis by using
effervescent floating matrix system (EFMS). The therapeutic limitations of DA-6034
caused by its low solubility in acidic conditions were overcome by using the EFMS,
which was designed to cause tablets to float in gastric fluid and release the drug
continuously. DA-6034 EFMS tablets showed enhanced gastroprotective effects in
gastric ulcer-induced beagle dogs, indicating the therapeutic potential of EFMS
tablets for the treatment of gastritis60.
Sungthongjeen, et al., (2008), designed a Floating multi-layer coated tablet based on
gas formation. The system consists of a drug-containing core tablet coated with a
protective layer (hydroxypropyl methylcellulose), a gas forming layer (sodium
bicarbonate) and a gas-entrapped membrane, respectively. Eudragit RL 30D was
chosen as a gas-entrapped membrane due to its high flexibility and high water
permeability. The obtained tablets enabled to float due to the CO2gas formation and
the gas entrapment by polymeric membrane. The floating tablets using direct-
compressed cores had shorter time to float and faster drug release than those using
wet-granulated cores. The increased amount of a gas forming agent did not affect time
to float but increased the drug release from the floating tablets while increasing
coating level of gas-entrapped membrane increased time to float and slightly retarded
drug release61.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 21
Nama, et al., (2008), developed the hydrodynamically balanced delivery system of
Clarithromycin in the treatment of Helicobacter pylori (H.pylori) mediated peptic
ulcer. By applying wet granulation technique floating tablets of Clarithromycin were
prepared and in vivo radiographic studies were performed with Barium sulphate
loaded formulation to justify the increased gastric residence time of the dosage form
in the stomach. It was concluded that formulation developed using 66.2%
Clarithromycin, 12% HPMC K4M polymer, 8% sodium bicarbonate gave floating lag
time less than 3 min with a floating time of 12 h, and an in vitro release profile very
near to the desired release. X-ray studies showed the enhanced gastric residence time
of the tablet to 220± 30 min. The mechanism of release of Clarithromycin from the
floating tablets is anomalous diffusion transport and follows zero order kinetics62.
Sanchez, et al., (2008) studied the effect of sodium bicarbonate (SB) on the swelling
behavior and the sustained release of floating systems with varied proportions of this
excipients and Metronidazole. Two polymers with different hydration characteristics,
Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. It was
found that Methocel matrices release the drug 10% to 15% faster than Carbopol
matrices. SB increases the cumulative amount of drug released from Methocel but not
that releasing from Carbopol. These results are attributed to the intrinsic polymer
properties, the barrier effect of CO2 bubbles, and the matrix volume expansion
produced after addition of SB63.
Lunio, et al., (2008), studied the 15 kinds of powders with different compression
mechanisms were used in the process of filling-binding substances in tablets with
pellets. Using 6 kN compression force in a single-stroke tablet press during 150 ms of
compression, damage to the polymer film and pellet core was found in all
formulations. As a result, the authors observed an increase of releasing rate of
verapamil hydrochloride (VH). A larger contact area between powders and pellets and
connected with this better protective properties were ensured by powders with time
independent compression mechanism (eg, D-sorbitol or D-mannitol) and it was found
that the releasing rate of Verapamil Hydrochloride from pellets compressed by rotary
tablet press with 6, 12, and 18 kN of compression force was similar to the releasing
rate from uncompressed pellets64.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 22
Genc, and Jalvand et al., (2008), prepared controlled release matrix tablets of
ketorolac tromethamine (KT) by direct compression technique using cellulose
derivatives as hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose
(HEC), and carboxymethyl cellulose (CMC) in different concentrations (10–20%).
The effect of polymer type and concentration was investigated on drug release by 23
factorial designs. For the quality control of matrix tablets, weight deviation, hardness,
friability, diameter–height ratio, content uniformity of KT, and in vitro dissolution
technique were performed. It was found that an increase in polymer content resulted
with a slow release rate of drug. According to the dissolution results, tablets prepared
with HPMC + HEC + CMC (F1 and F8) were found to be the most suitable
formulation for KT. About 99.27% KT was released from F8 in 7 h65.
Strubing, et al., (2008), developed a Floating Kollidon SR matrix tablets containing
Propranolol HCl and characterized with respect to drug release characteristics and
floating strength. Drug release kinetics was evaluated using the Korsmeyer-Peppas
model and found to be governed by Fickian diffusion. Tablet floating started
immediately and continued for 24 h. Floating strength was related to Kollidon SR
level with improved floating characteristics for samples with a high polymer/drug
ratio. The influence of the polymer content on swelling characteristics was found to
be only marginal66.
Kerc and Opara et al., (2007) was developed a new peroral amoxicillin/clavulanate
therapeutic system composed of immediate release tablet and controlled release
floating capsule and evaluated by in vivo bioavailability study. Pharmacokinetic
parameters for amoxicillin and clavulanic acid of the new therapeutic system: AUCt,
AUCi, Cmax, Tmax,kel,T1/2 and additionally for amoxicillin T4 and T2 were
calculated from plasma level. The study confirmed enhanced pharmacokinetic
parameters of a newly developed therapeutic system containing 1500 mg of
amoxicillin and 125 mg of clavulanic acid. Prolonged time over MIC of amoxicillin in
relation to a regular immediate release amoxicillin/clavulanate formulation was
confirmed67.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 23
Sriamornsak, et al., (2007), prepared matrix tablets by direct compression using
different grades of alginate. The effect of some factors (i.e. particle size of drug,
additive used, and pH of medium) on drug release from alginate-based matrix tablets
was investigated. The alginate-based matrix tablets swelled or eroded while in contact
with the aqueous medium and formed a continuous gel layer or underwent
combination of swelling and erosion. The presence of ammonium or calcium salts
induced tablet disintegration in acidic medium. Release studies showed that all
investigated factors influence the drug release. The extent of matrix swelling, erosion,
and diffusion of drug determined the kinetics as well as mechanism of drug release
from alginate-based matrix tablets. Most of the release data in acidic medium showed
a good fit into Korsmeyer–Peppas equation but fitted well with zero-order release
model, in neutral medium68.
Raval, et al.,(2007) were evaluated ranitidine hydrochloride floating matrix tablet
based on low density power effect of formulation and processing parameters on drug
release. The tablet were prepared by the direct compression technique,using
hydrophilic matrix polymers HPMC K4M, HPMC K15M, HPMC K100M,Sodium
alginate psyllum, sesbania gum, guar gum,and gum acacia,with or without density
copolymer.
Badve, et al., (2007) has developed to overcome limitations of various approaches for
imparting buoyancy; hollow/porous beads were prepared by simple process of acid-
base reaction during ionotropic crosslinsking.
Tang, et al., (2007) has developed Floating beads of three kinds of drugs with
different hydrophilicities; ibuprofen, niacinamide and metoclopramide HCL were
tested in the study. They concluded that the hydrophobic drug ibuprofen was released
in a sustained manner for 24 h. due to the oil partitioning. With suitable modification,
the beads were able to also release the hydrophilic drugs, niacinamide and
metoclopramide HCL, for a similar duration.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 24
Wu, et al., (2007), measured the pore size distribution in tablets with a morphological
sieve (SEM micrographs) and compared it with result obtained with mercury
porosimeter. The pore size distribution in these images was determined with a
technique referred to as a morphological sieve. The influence of the size of the
discarded structures on the total porosity and the pore size distribution was
investigated using the small ‘floating’ grains. Based on these results with the
experimentally determined porosity, a maximum size for the structures that were to be
removed was determined. The resulting pore size distributions were in the same order
of magnitude as the results obtained with mercury porosimetry. Both methods display
a comparable relative shift of the pore size distributions to larger sizes for tablets with
increasing particle size69.
Jaimini, et al., (2007), prepared floating tablets of famotidine using methocel K100M
and methocel K15M by effervescent technique. Sodium bicarbonate was incorporated
as a gas-generating agent. The floating tablets were evaluated for uniformity of
weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies
and effect of citric acid on drug release profile and floating properties was
investigated. A combination of sodium bicarbonate (130mg) and citric acid (10mg)
was found to achieve optimum in vitro buoyancy. The tablets with methocel K100
were found to float for longer duration as compared with formulations containing
methocel K15M. The drug release from the tablets was sufficiently sustained and non-
Fickian transport of the drug from tablets was confirmed70.
Patel and Patel et al., (2007), investigated the use of xanthan gum and guar gum for
development of floating drug delivery system of dipyridamole using factorial design.
The content of polymer blends (X1) and ratio of xanthan gum to guar gum (X2) were
selected as independent variables. The diffusion exponent (n), release rate constant
(k), percentage drug release at 1 hr (Q1) and 6 hr (Q6) were selected as dependent
variables. Tablets of all batches had desired buoyancy characteristics. Multiple
regression analysis with two way ANOVA revealed that both the factors had
statistically significant influence on the response studied (p < 0.05). It was concluded
that the ratio of xanthan gum to guar gum had equal or dominant role as controlling
factor on kinetics of drug release compared to content of polymer blends71.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 25
Gambhire, et al., (2007), prepared an oral matrix tablet of diltiazem HCl (DTZ) by
direct compression technique, using polymers such as hydroxypropylmethylcellulose
(HPMC, Methocel K100M CR), Compritol 888 ATO, alone or in combination to
prolong gastric residence time & increase bioavailability. Sodium bicarnonate was
incorporated as gas-generating agent. The effects of sodium bicarbonate and succinic
acid on drug release profile and floating properties were investigated. A 32 factorial
design was applied to systematically optimize the drug release profile. It was
concluded that high level of both Methocel K100M CR (X1) and Compritol 888 ATO
(X2) favors the preparation of floating controlled release of DTZ tablets. All the
prepration follows the Koresmayer Peppas model, which had a higher value of
correlation coefficient (r) while tablet hardness had little or no effect on the release
kinetics72.
Ali, et al., (2007), developed a hydrodynamically balanced system for celecoxib as
single-unit floating capsules using various grades of low-density polymers. The
formulation was optimized on the basis of in vitro buoyancy and in vitro release in
citrate phosphate buffer pH 3.0 (with 1% sodium lauryl sulfate) and found that
capsules prepared with polyethylene oxide 60K and Eudragit RL100 gave the best in
vitro percentage release and were used as the optimized formulation. Gamma
imaging was performed in rabbits to assess the buoyancy of the optimized
formulation. The optimized formulation remained buoyant during 5 hours of gamma
scintigraphic studies in rabbits73.
Patel, et al., (2007), prepared a gastroretentive drug delivery system of
carbamazepine using HPMC, sodium bicarbonate, and EC as matrixing agent, gas-
generating agent, and floating enhancer, respectively. A simplex lattice design was
applied to investigate the combined effect of 3 formulation variables (i.e, amount of
HPMC (X1), EC (X2), and sodium bicarbonate (X3). Results of multiple regression
analysis indicated that low levels of X1 and X2 and a high level of X3 should be used
to manufacture the tablet formulation with desired in vitro floating time and
dissolution. Formulation S3 was selected as a promising formulation and was found
stable at 400C temperature and 75% RH for 3 months74.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 26
Dorozynski, et al., (2007), developed a System for Simultaneous Dissolution Studies
and Magnetic Resonance Imaging of Water Transport in Hydrodynamically Balanced
Systems and concluded that, the MRI methods combined with the dissolution studies
provide insight into the phenomena occurring when the dosage form comes into
contact with aqueous fluids. The MRI images allow one to observe the solvent
penetration into the hydrophilic matrix and the hydrogel formation. The data obtained
in the MRI studies complement information obtained from the dissolution studies.
The analysis of MRI images support the explanation of differences in the drug-
releasing or floating properties of HBS75.
Fukuda, et al., (2006), investigated the influence of sodium bicarbonate on
physicochemical properties of controlled release hotmelt extruded tablets (HME)
containig Eudragit® RS PO and/or Eudragit® E PO using Acetohydroxamic acid and
chlorpheniramine maleate as model drug. The drug release properties and buoyancy in
media for HME tablets and directly compressed (DC) tablets were investigated. The
HME tablets prepared from the powder blend containing both Eudragit® RS PO and
sodium bicarbonate exhibited sustained release properties and the tablets floated on
the surface of the media for 24 h and the drug release profile and buoyancy of the
floating HME tablets were stable when stored at 400c/75%RH for 3 months76.
Rahman, et al., (2006), developed a bilayer floating tablets (BFT) of captopril using
HPMC K-15 M, PVP K-30 and Carbapol 934P, alone or in combinations with the
drug formulations were evaluated for the various physicochemical testing including
dissolution studies. It was concluded that final formulation released 95% drug in 24hr
in vitro, while the floating lag time was 10 min and tablet remained floatable through
out all studies. Final formulation followed the Higuchi release model and showed no
significance change in the physical appearance, drug content, floatability or in vitro
dissolution pattern after storage at 450C/75% RH for three months. Placebo
formulation containing barium sulfate in the release layer administered to the human
volunteer for in-vivo X-ray studies showed that BFT had significantly increased the
gastric residence time77.
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 27
Xiaoqiang, et al., (2006), developed floating matrix dosage form for phenoporlamine
hydrochloride because of its short biological half life. Hydroxypropyl methylcellulose
K4M and Carbopol 971P NF were used in formulating the hydrogel drug delivery
system. The dissolution profiles of all tablets showed non-Fickian diffusion in
simulated gastric fluid. In vivo evaluations of these formulations of phenoporlamine
hydrochloride were conducted in six healthy male human volunteers to compare the
sustained release tablets with immediate release tablets. Data obtained in these studies
demonstrated that the floating matrix tablet containing more Carbopol was capable of
sustained delivery of the drug for longer periods with increased bioavailability and the
relative bioavailability of formulation (containing 25% Carbopol 971P NF, 8.3%
HPMC K4M) showed the best bioequivalency to the reference tablet78.
Karande and Yeole et al., (2006), evaluated and compared the different official and
unofficial dissolution test of floating drug delivery systems. Establishment of in vitro
dissolution and in vivo performance (IVIVR), and quality control of solid dosage
forms depends mainly upon dissolution testing (Modified dissolution test) and
concluded that the modified method provides a more reproducible dissolution
profiles, eliminates the risk of floating dosage forms adhering to the paddles, and
simplifies the sampling procedure by producing smaller volume of dissolution
medium. The modified dissolution assessment of the tablet dosage form as it more
closely simulates most of the in vivo conditions like gastric volume, acid secretion
rate79.
Narendra, et al., (2006), developed and optimized gastric floating drug delivery
system (GFDDS) of metoprolol tartrate (MT) by applying a 23 factorial design. In this
polymer content-to-drug ratio (X1), polymer-to-polymer ratio (X2), and different
viscosity grades of Hydroxypropyl methylcellulose (HPMC) (X3) as independent
variables. Four dependent variables were considered: percentage of MT release at 8
hours, t50%, diffusion coefficient, and floating time. The results indicate that X1 and
X2 significantly affected the floating time-release properties, but the effect of
different viscosity grades of HPMC (K4M and K10M) was not significant. Regression
analysis and numerical optimization were performed to identify the best formulation.
Fickian release transport was confirmed as the release mechanism from the optimized
formulation80.
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 28
Merchant, et al., (2006), developed a floating tablet of cefpodoximme using
Hydroxypropyl Methylcellulose and concluded that the hydrophilic matrix of HPMC
controlled the cefpodoxime proxetil release effectively for 24 hours. The formulation
showed acceptable pharmacotechnical properties and assay requirements. In vitro
dissolution studies indicated a sustained-release pattern throughout 24 hours of the
study that was comparable to the theoretical release profile. Drug release kinetics
indicated that drug release was best explained by Higuchi’s equation, as these plots
showed the highest linearity (R2 = 0.9734). Korsmeyer’s plots indicated an n value of
0.57, which was indicative of an anomalous diffusion mechanism or diffusion coupled
with erosion; hence, the drug release was controlled by more than one process.
Hixson-Crowell plots indicated a change in surface area and diameter of the tablets
with the progressive dissolution of the matrix as a function of time81.
Nakagawa, et al., (2006), prepared a novel intragastric floating drug delivery system
(FDDS) by pulsed plasma-irradiation on the double-compressed tablet of 5-
Fluorouracil (5-FU) as a core material with outer layer composed of a 68/17/15
weight ratio of Povidone (PVP), Eudragit RL (E-RL) and NaHCO3. The plasma heat
flux caused the thermal decomposition of NaHCO3 to generate carbon dioxide and the
resultant gases were trapped in bulk phase of outer layer, so that the tablets turned to
have a lower density than the gastric contents and remained buoyant in simulated
gastric fluid for a prolonged period of time. In addition, the release of 5-FU from the
tablet is sustained by occurrence of plasma-induced crosslink reaction on the outer
layer of tablet and the release rate of 5-FU can be well controlled by plasma
operational conditions82.
Patel, et al., (2006), formulated and evaluated the floating drug delivery system
(tablets) containing Clarithromycin for the treatment of Helicobacter pylori by using
containing hydroxypropyl Methylcellulose (HPMC), drug and different additives
compressed using wet granulation and D-optimal design technique. The study showed
that tablet composition and mechanical strength have great influence on the floating
properties and drug release. Incorporation of gas-generating agent together with
polymer improved drug release, besides optimal floating (floating lag time <30 s; total
floating time >10 h). The optimized formulation was obtained using 62.5%
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 29
clarithromycin, 4.95% HPMC K15M, 18.09% HPMC K4M, 12.96% sodium
bicarbonate which gave floating lag time < 30 s with a total floating time > 10 h, in
vitro release profile very near to the target in vitro release profile and follows
anomalous diffusion as well as zero order pattern of release83.
Chvanpatil, et al., (2006) prepared new gastroretentive sustained release delivery
system was developed with floating, swellable and bioadhesive properties. All these
properties were optimized and evaluated. Various release retarding polymers like
psyllium husk, HPMC K100M and a swelling agent, crosspovidone in combinations
were tried and optimized to get the release profile for 24 h. The in vitro drug release
followed Higuchi kinetics and the drug release mechanism was found to be of
anomalous or non-Fickian type. They also compared the release with marketed
preparation, in case of developed formulation the value of n was found to be 0.5766
and in case of marketed preparation it was 0.5718 indicates anomalous transport. The
swelling properties were increased with increasing crosspovidone concentration and
contributed significantly in drug release from the tablet matrix. The bioadhesive
property of the developed formulation was found to be significant (P < 0.005) in
combination as compared to HPMC K100M and psyllium husk alone.
Rajanikanth, et al., (2006) prepared a novel floating in situ gelling system of
amoxicillin for eradication of Helicobacter pylori. Gellan based amoxicillin floating
in situ gelling systems (AFIG) were prepared by dissolving varying concentrations of
gellan gum in deionized water containing sodium citrate, to which varying
concentrations of drug and calcium carbonate, as gas-forming agent, was added and
dissolved by stirring. The formulation variables like concentration of gellan gum and
calcium carbonate significantly affected the in vitro drug release from the prepared
AFIG. The in vivo H. pylori clearance efficacy of prepared AFIG in reference to
amoxicillin suspension following repeated oral administration to H. pylori infected
Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and
by a microbial culture method. AFIG showed a significant anti-H. pylori effect in the
in vivo gerbil model. It was noted that the required amount of amoxicillin for
eradication of H. pylori was 10 times less in AFIG than from the corresponding
amoxicillin suspension.
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 30
Bardonnet, et al., (2006) had described in their review on gastroretentive dosage
form for in special case of H. pylori that different approaches for GRDDS and also
described Stomach physiopathology following H. pylori infection and Gastroretentive
dosage forms against H. pylori.
Streubel, et al., (2006) had mentioned in their review; bioavailability of drugs with an
absorption window in the upper small intestine is generally limited with conventional
pharmaceutical dosage forms. The residence time of such systems and, thus, of their
drug release into the stomach and upper intestine is often short. To overcome this
restriction and to increase the bioavailability of these drugs, controlled drug delivery
systems with a prolonged residence time in the stomach can be used. Approaches to
achieving prolonged residence times of the devices in the upper part of the
gastrointestinal tract include the use of bioadhesive, sizeincreasing, and floating drug
delivery systems.
Songjun, et al. (2006) proposed a common model to interpret release process from a
polymer matrix. It often involves drug diffusion, interface movement and various
interactions. They also suggested micromechanism analysis of polymer based
controlled release.
Jamzad, et al., (2006) developed a monolithic matrix system to deliver Glipizide over
24 hours. The polymer matrix comprised of swellable hydrophilic polymer (HPMC)
or erodible polyethylene oxide (PEO).The tablets were prepared employing direct
compression technique. The inter-relationship between matrix hydration and erosion
was determined and analysed under the dissolution test conditions.
Tomoya,et al.(2006) was evaluated preparation of floating drug delivery system by
plasma technique by A novel intragastric floating drug delivery system has been
prepared by pulsed plasma –irradiation on the double compressed tablet of 5-
fluorouracil (5-FU) as a core material withouter layer composed of a weight of
povidone (PVP),Eudragit RL and NAHCO3
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 31
Srivastava, et al., (2005), developed the Floating matrix tablets of atenolol by direct
compression technique, using polymers such as hydroxypropyl methylcellulose
(HPMC K15M, K4M), guargum (GG), and sodium carboxymethylcellulose (SCMC),
alone or in combination with other standard excipients. Tablets were evaluated for
physical characteristics viz. hardness, swelling index, floating capacity, thickness,
weight variation and in vitro release characteristics for 8 hr. The effect of effervescent
on buoyancy and drug release pattern was also studied. In vitro release mechanism
was evaluated by linear regression analysis. GG and SCMC based matrix tablets
showed significantly greater swelling indices compared with other batches. The
tablets exhibited controlled and prolonged drug release profiles while floating over
the dissolution medium84.
Patel, et al., (2005), formulated and evaluated the floating tablets of Ranitidine
Hydrochlorilde. Formulation were optimized for type of fillers (Avicel PH 102 and
tablettose) and different viscosity grades of polymers (HPMC K 100 M HPMC K15
and HPMC K4 M).It was found that viscosity had a major influence on drug release
from hydrophilic matrix as well as floating properties and dissolution profiles follows
the Higuchi Equation i.e drug release by diffusion mechanism. Optimized formulation
showed the effect of hardness on floating properties as the increase in hardness
increased the floating lag time due to decrease in porosity as hardness increases85.
Chavanpatil, et al., (2005) prepared sustained release (SR)-gastroretentive dosage
forms (GRDF) for ofloxacin preferably once daily. The design of the delivery system
was based on the sustained release formulation, with floating and swelling features in
order to prolong the gastric retention time of the drug delivery systems. Different
polymers, such as psyllium husk, HPMC K100M, crospovidone and its combinations
were tried in order to get the desired sustained release profile over a period of 24 hrs.
Various formulations were evaluated for buoyancy lag time, duration of buoyancy,
dimensional stability, drug content and in vitro drug release profile. It was found that
dimensional stability of the formulation increases with the increasing psyllium husk
concentration. It was also found that in vitro drug release rate increased with
increasing amount of crospovidone due to the increased water uptake, and hence
increased driving force for drug release. The optimized formulation was subjected to
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 32
stability studies at different temperature and humidity conditions as per ICH
guidelines.
Sawicki and Lunio, et al., (2005) studied the compressibility of floating pellets with
verapamil hydrochloride (VH) coated with dispersion Kollicoat SR 30 D. In
experiments three plasticizers were examined-propylene glycol, triethyl citrate and
dibuthyl sebecate (all at concentration of 10%). It was found that Verapamil
hydrochloride release from pellets coated by the films of the same thickness (70 mm),
however, containing plasticizers is considerably different. Two kinds of cellulose,
microcrystalline and powdered, and sodium hydrocarbonate were the main
components of pellet core. The best formulation was evaluated taking into account the
effect of compression force and tablet hardness and friability, and pellet
agglomeration and flotation. Tablet cross-section photographs were taken confirming
necessary coating film thickness preventing their deformation caused by compressing
into tablets86.
Dave, et al., (2004), prepared gastroretentive drug delivery system of ranitidine
hydrochloride. Guar gum, Xanthan gum, and Hydroxypropyl methylcellulose were
evaluated for gel-forming properties. Sodium bicarbonate was incorporated as gas-
generating agent. A 32 full factorial design was applied to systemically optimize the
drug release profile. The results of the full factorial design indicated that low amount
of citric acid and a high amount of stearic acid favors sustained release of ranitidine
hydrochloride from a gastro retentive formulation. The similarity factor f2 was applied
between the factorial design batches and the theoretical dissolution profile. No
significant difference was observed between the desired release profile and test
batches and this similarity also reflected in t50 (~214 minutes) and t80 (~537 minutes)
values87.
Shimpi, et al., (2004), studied the develpoment of multi unit floating systems of a
highly water soluble Diltiazem Hydrochloride using Gelucire-43/01. Diltiazem
Hydrochloride - Gelucire-43/01 granules were prepared by melt granulation
techniques. Granules were retained in stomach atleast for 6 hrs. Approximately 65-
80% drug was released over 6 hrs with initial fast release from the surface. In
conclusion hydrophobic lipid Gelucire-43/01 can be considered as an effective carrier
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 33
for design of a multi unit floating drug delivery system of highly water soluble drugs
such as Diltiazem Hcl88.
Amin, et al., (2004) developed a gastroretentive drug delivery system of ranitidine
hydrochloride was designed using guar gum, xanthan gum, and HPMC. 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. The
addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. 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 amount of stearic
acid favor sustained release of ranitidine HCl from a gastro retentive formulation.
Rani and Mishra, et al., (2004), compared In-vitro and In-vivo evaluation of
fabricated matrix (FM), osmotic matrix (OM), and osmotic pump (OP) tablets for
controlled delivery of diclofenac sodium (DS). All the fabricated formulations
showed more prolonged and controlled DS release compared with commercial tablets
studied. The OM and OP tablets, however, performed better than the matrix tablets.
The rate and extent of drug release from FM1 matrix tablets (single polymer) was
significantly different from that of FM2 (admixed polymers). Type of porosigenic
agents and osmogens also influenced the drug release. Analysis of in vitro data by
regression coefficient analysis revealed zero-order release kinetics for OM and OP
tablets, while FM tablets exhibited Higuchi kinetics. In vivo results indicated
prolonged blood levels with delayed peak and improved bioavailability for fabricated
tablets compared to commercial tablets. It was concluded that the osmotic matrix and
osmotic pump tablets could provide more prolonged, controlled, and gastrointestinal
environmental independent DS release that may result in an improved therapeutic
efficacy and patient compliance89.
Albarran and Robles, et al., (2004), studied the effect of formulation and Process
variables on the release behavior of Amoxicillin matrix Tablets. In vitro dissolution,
at pH 1.2, of amoxicillin sustained release tablets had been studied varying the
proportion of Carbopol 971P NF and sodium alginate as well as the ethanol/water
proportion in the granulation fluid. Matrices with increasing proportions of sodium
alginate showed increasing values of the exponent indicative of the release
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 34
mechanism (n) and increasing release constant values (k). Alginate proportions of
80% produce near zero order release profiles. Alginate matrices granulated with
different ethanol/water proportions showed no significant changes in the amoxicillin
release profile. There is a trend toward increasing floating times with increasing
Carbopol 971P NF proportions90.
Kiran, et al., (2004), studied the effect of drug solubility and different excipients
(PEG 4000, PEG 10000 and stearic acid) on floating behavior and release from
glyceryl monooleate matrices using Chlorpheniramine maleate (CPM) and diazepam
(DZP) as model drugs and concluded that water uptake increased with increase in the
loading of polar drug (CPM) and decreased with non-polar drug (DZP). PEGs
increased the release up to certain concentration and decreased thereafter and drug
released decreased linearly with concentration of stearic acid. Thus the selection of
suitable excipients depending on polarity of drug could help to modulate the
floatability and release profile from GMO matrices91.
Lis, et al., (2003), studied the effect of formulation variables on drug release and
floating properties of the delivery system. Hydroxypropyl methylcellulose (HPMC) of
different viscosity grades and Carbopol 934P (CP934) were used in formulating the
Gastric Floating Drug Delivery System (GFDDS) employing 2 × 3 full factorial
design. It was concluded that both HPMC viscosity, the presence of Carbopol and
their interaction had significant impact on the release and floating properties of the
delivery system. The decrease in the release rate was observed with an increase in the
viscosity of the polymeric system92.
Chein, et al. (2003) prepared gastric floating drug delivery system (GFDDS) using
2×3 full factorial design. Hydroxypropyl methylcellulose (HPMC) of different
viscosity grades and Carbopol 934P (CP934) were used in formulating. It was found
that both HPMC viscosity, the presence of Carbopol and their interaction had
significant impact on the release and floating properties of the delivery system. The
decrease in the release rate was observed with an increase in the viscosity of the
polymeric system. Polymer with lower viscosity (HPMC K100LV) was shown to be
beneficial than higher viscosity polymer (K4M) in improving the floating properties
of GFDDS. Incorporation of Carbopol, however, was found to compromise the
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 35
floating capacity of GFDDS and release rate of calcium. The observed difference in
the drug release and the floating properties of GFDDS could be attributed to the
difference in the basic properties of three polymers (HPMC K4M, K100LV and
CP934) due to their water uptake potential and functional group substitution.
Streubel, et al., (2003), prepared Floating matrix tablets based on low density foam
powder (propylene foam powder) and studied its effects of formulation and
processing parameters on drug release. They concluded that The highly porous foam
powder provided low density and, thus, excellent in vitro floating behavior of the
tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N
HCl at 370C. 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)93.
Huang, et al., (2003), investigated the effect of three process variables: distribution of
hydroxypropyl methylcellulose (HPMC) within the tablet matrix, amount of water for
granulation, and tablet hardness on drug release from the hydrophilic matrix tablets.
Tablets were made both by direct compression as well as wet granulation method. The
dissolution parameters obtained were statistically analyzed using a multilevel
factorial-design approach to study the influence of the various process variables on
drug release from the tablets. Results indicated that a change in the manufacturing
process could yield significantly dissimilar dissolution profiles for the same
formulation; overgranulation could lead to tablets showing hardness-dependent drug-
release characteristics. Studies showed that intergranular addition of a partial amount
of HPMC provided a significant advantage in making the formulation more robust
over intragranular addition. Dissolution profiles obtained for these tablets were
relatively less dependent on tablet hardness irrespective of the amount of water added
during granulation94.
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 36
Klausner, et al., (2003), performed the in-vivo evaluation in dogs using levodopa
gastroretentive dosage forms. They developed a novel GRDF, based on unfolding of
polymeric membranes, that combines extended dimensions with high rigidity, and to
examine the pharmacokinetics of levodopa compounded in the GRDF in beagle
dogs.The successful CR-G RDF maintained threpeutic levodopa concentration(>500
ng ml-1) over 9 h. in comparison to non- gastroretentive CR-particles. And oral
solution, mean absorption time was significantly extended. These outcomes
demonstrate that the CR-GRDF may be used to improve levodopa therapy and can be
applied to extend the absorption of other narrow absorption window drugs that require
continuous input95.
Bhaskaran, et al., (2002), studied the novel approach to drug delivery via hydrogel
for Diltiazem hydrochloride.Hydrogel matrix tablet of Diltiazem HCL developed
using HPMC and sodium CMC to attain zero order release. The release studies show
Higuchian pattern. When the optimum mixture of HPMC and Sod.CMC used, the
drug release follows zero order rate. The mechanism of diffusion was explained by
Peppas equation96.
Wei, et al., (2001), developed a new kind of two-layer floating tablet for gastric
retention (TFTGR) with cisapride as a model drug. The in vitro drug release was
determined, and the resultant buoyancy and the time-buoyancy curve were plotted.
Due to sodium bicarbonate added to the floating layer, when immersed in simulated
gastric fluid (SGF) the tablet expands and rises to the surface, where the drug is
gradually released. They concluded that in vitro drug release of this kind of two-layer
dosage was controlled by the amount of hydroxypropylmethylcellulose (More HPMC,
the slower the drug releases) in the drug-loading layer. Because cisapride has greater
solubility in SGF than simulated intestinal fluid (SIF), its in vitro drug dissolution in
SGF is faster than in SIF97.
Lis, et al., (2001), developed an optimized gastric floating drug delivery system. A
central, composite Box-Wilson design for the controlled release of calcium was used
with 3 formulation variables: X1 (hydroxypropyl methylcellulose [HPMC] loading),
X2 (citric acid loading), and X3 (magnesium stearate loading). Twenty formulations
were prepared, and dissolution studies and floating kinetics were performed on these
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 37
formulations. All 3 formulation variables were found to be significant for the release
properties (P < .05), while only HPMC loading was found to be significant for
floating properties. Optimization of the formulations was achieved by applying the
constrained optimization. The optimized formulation delivered calcium at the release
rate of 40 mg/hr, with predicted n and T50% values at 0.93 and 3.29 hours,
respectively. Experimentally, calcium was observed to release from the optimized
formulation with n and T50% values of 0.89 (± 0.10) and 3.20 (± 0.21) hours, which
showed an excellent agreement98.
Sasa, et al., (2000), investigated the development of floating matrix tablets containing
hydroxyl propyl methyl cellulose (HPMC), drug and different additives, which after
oral administration are designed to prolong the gastric residence time, increase the
drug bioavailability and diminish the side effects of irritating drugs The investigation
showed that tablet composition and mechanical strength have the greatest influence in
the floating properties and drug release The drug release from the tablets was
sufficiently sustained (more than 8h) and non-Fickian transport of the drug from
tablets was found. Radiological evidence suggests that, the formulated tablets did not
adhere to the stomach mucus and that the mean gastric residence time was prolonged
(>4h)99.
Nur and Zhang, et al., (2000), developed floating tablets of captopril using HPMC
(4000 and 15 000 cps) and carbopol 934P. In vitro buoyancy studies revealed that
tablets of 2 kg/cm2 hardness after immersion into the floating media floated
immediately and tablets with hardness 4 kg/cm2 sank for 3 to 4 minutes and then
came to the surface. Tablets in both cases remained floating for 24 hours. The tablet
with 8 kg/cm2 hardness showed no floating capability. 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 achieved100.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 38
Durig , et al., (2000), et al investigated the extent to which hydrophilic matrix tablets
with a propensity to stick to the dissolution apparatus and/or float are susceptible to
variations in hydrodynamic conditions during dissolution testing. Swellable
hydrocolloid (guar) matrix tablets containing verapamil HCl were evaluated using
USP dissolution apparatus I and II with two additional configurations where an
additional single ring and mesh device or a double mesh device was located below the
paddle in the dissolution vessel.Tablets were placed on top of the single mesh device
or in the compartment formed by the two mesh surfaces of the double mesh device. In
all cases near linear (n≥0.82) release profiles were observed and concluded that use of
a double mesh device may therefore provide an alternative to current compendial
dissolution methods when the reliable determination of the true release kinetics of
floating and sticking delivery systems is desired101.
Ozdemir, et al., (2000), designed a furosemide (FR), a floating dosage form with
controlled release for the purpose of enhancement of bioavailability of furosemide.
Because of the lower solubility of active material in the gastric medium, it was first
enhanced by preparing an inclusion complex of FR with beta-cyclodextrin (b-CD) in a
1:1 proportion using the kneading method further bilayer floating tablets were
prepared. It was determined by radiographs that floating tablets prepared by adding
BaSO4 stayed in the stomach for 6 hr. Further, values of the area under the plasma
concentration-time curve (AUC) obtained with the floating dosage form were about
1.8 times those of the conventional FR tablet in blood analyses; maximum and
minimum plasma concentrations were also found to be between the desired limits. In
urine analyses, the peak diuretic effect seen in classical preparations was decreased
and prolonged in floating dosage forms102.
Fassihi, et al., (1999), developed a drug treatment (tetracycline, metronidazole and
bismuth salt) of Helicobacter pylori associated peptic ulcers. The design of the
delivery system was based on the swellable asymmetric triple layer tablet approach,
with floating feature in order to prolong the gastric retention time of the delivery
system. Results demonstrated that sustained delivery of tetracycline and
metronidazole over 6–8 h can be easily achieved while the tablet remained afloat103.
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Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 39
Garg and Gupta, et al., (2008), reviewed that controlled release (CR) dosage forms
have been extensively used to improve therapy with several important drugs.
Incorporation of the drug in a controlled release gastroretentive dosage forms (CR-
GRDF) which can remain in the gastric region for several hours would significantly
prolong the gastric residence time of drugs and improve bioavailability, reduce drug
waste, and enhance the solubility of drugs that are less soluble in high pH
environment. Gastroretention would also facilitate local drug delivery to the stomach
and proximal small intestine. Thus, gastroretention could help to provide greater
availability of new products and consequently improved therapeutic activity and
substantial benefits to patients. Controlled gastric retention of solid dosage form may
be achieved by the mechanism of floatation, mucoadhesion, sedimentation expansion
or by a modified shaped system104.
Waterman, et al., (2007), reviewed that the promise of gastric retentive drug delivery
systems propagated numerous investigations and the formation of a number of
companies. Three technologies had involved a substantial number of human clinical
trials: mucoadhesion, density modification, and expansion. Standard,
nondisintegrating controlled release tablets can display significant gastric retention
times, with that retention time being proportional to the calorie intake. When these
data for standard tablets are factored in, gastric retention technologies do not appear to
offer significant additional retention times. Although the goal remains valuable, the
promise of gastric retentive drug delivery systems remains unfulfilled at this time105.
Arora, et al., (2005). Reviewed that the recent developments of FDDS are including
the physiological and formulation variables affecting gastric retention, approaches to
design single-unit and multiple-unit floating systems, and their classification and
formulation aspects are covered in detail. This review also summarizes the in vitro
techniques, in vivo studies to evaluate the performance and application of floating
systems, and applications of these systems. These systems were useful to several
problems encountered during the development of a pharmaceutical dosage form106.
Talukder and Fassihi, et al., (2004), reviewed that various attempts have been made
to develop gastroretentive delivery systems. For example, floating, swelling,
mucoadhesive, and high-density systems have been developed to increase gastric
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 40
retention time of the dosage forms. It was known that differences in gastric
physiology, such as, gastric pH, and motility exhibit both intra as well as inter-subject
variability demonstrating significant impact on gastric retention time and drug
delivery behavior. Nevertheless, some floating devices have shown promising
results107.
Klausner, et al., (2003) reviewed that Expandable gastroretentive dosage forms
(GRDFs). These GRDFs are easily swallowed and reach a significantly larger size in
the stomach due to swelling or unfolding processes that prolong their gastric retention
time (GRT). After drug release, their dimensions are minimized with subsequent
evacuation from the stomach. Gastroretentivity is enhanced by the combination of
substantial dimensions with high rigidity of the dosage form to withstand the
peristalsis and mechanical contractility of the stomach. Positive results were obtained
in preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow
absorption window drugs compounded in such systems have improved in vivo
absorption properties. These findings are an important step towards the
implementation of expandable GRDFs in the clinical setting108.
Garg and Sharma, et al., (2003) reviewed that the control of drug release profiles
has been a major aim of pharmaceutical research and development in the past two
decades, the control of GI transit profiles could be the focus of the next two decades
and might result in the availability of new products with new therapeutic possibilities
and substantial benefits for patients. Soon, the so-called ‘once-a-day’ formulations
may be replaced by novel gastroretentive products with release and absorption phases
of approximately 24 hours109.
Choi, et al., (2002) 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. 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
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 41
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%).
El-Kamel, et al. (2001) prepared floating microparticles of ketoprofen by emulsion
solvent diffusion technique. Four different ratios of Eudragit S 100 with Eudragit RL
were used. The formulation containing 1:1 ratio of the 2 above-mentioned polymers
exhibited high percentage of floating particles in all the examined media as evidenced
by the percentage of particles floated at different time intervals. This can be attributed
to the low bulk density, high packing velocity, and high packing factor
Baumgartner, et al. (2000) developed a matrix-floating tablet incorporating a high
dose of freely soluble drug. The formulation containing 54.7% of drug, HPMC K4 M,
Avicel PH 101, and a gas-generating agent gave the best results. It took 30 seconds to
become buoyant.
Fell, et al. (2000) prepared floating alginate beads incorporating amoxycillin. The
beads were produced by dropwise addition of alginate into calcium chloride solution,
followed by removal of gel beads and freeze-drying. The beads containing the
dissolved drug remained buoyant for 20 hours and high drug-loading levels were
achieved.
Singh and Kim, et al., (2000), reviewed that in recent years scientific and
technological advancements had been made in the research and development of rate-
controlled oral drug delivery systems by overcoming physiological adversities, such
as short gastric residence times (GRT) and unpredictable gastric emptying times
(GET). Several approaches were currently utilized in the prolongation of the GRT,
including floating drug delivery systems (FDDS), also known as hydrodynamically
balanced systems (HBS), swelling and expanding systems, polymeric bioadhesive
systems, modified-shape systems, high-density systems, and other delayed gastric
emptying devices110.
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 42
Steingoetter, et al., (2003) determined the influence of meal composition and timing
of tablet administration on the intragastric performance of a gastric-retentive floating
tablet using magnetic resonance imaging in the sitting position. Results showed that
the tablet showed persistent good intragastric floating performance independent of
meal composition. Unfavourable timing of tablet administration had a minor effect on
the intragastric tablet residence time and floating performance111.
Dave, et al., (2004) prepared a gastro retentive drug delivery system of ranitidine
hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were
evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-
generating agent. The effects of citric acid and stearic acid on drug release profile and
floating properties were investigated. The addition of stearic acid reduces the drug
dissolution due to its hydrophobic nature. The results of the full factorial design
indicated that a low amount of citric acid and a high amount of stearic acid favors
sustained release of ranitidine hydrochloride from a gastroretentive formulation112.
Shyam, et al., (2004) investigate the application of Gelucire 43/01 for the design of
multi-unit floating systems of a highly water-soluble drug diltiazem HCl. Diltiazem
HCl-Gelucire 43/01 granules were prepared by melt granulation technique. The
granules were evaluated for in vitro and in vivo floating ability, surface topography,
and in vitro drug release. Aging effect on storage was evaluated using scanning
electron microscopy, hot stage polarizing microscopy (HSPM), differential scanning
calorimetry (DSC), and in vitro drug release. Granules were retained in stomach at
least for 6 hours113.
Hoffman, et al., (2004) determined the complexity of the pharmacokinetics and
pharmacodyanamics factors that influence the treatment benefits of controlled release
dosage form and summarizes the results of in vivo investigations in animal models
(rats and dogs) and in human subjects. They found that a CR-GRDF formulation was
superior to the other modes of administration for levodopa and riboflavin, but not for
metformin114.
Research Work Review
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 43
Gohel, et al., (2004) developed a more relevant in vitro dissolution method to
evaluate a carbamazepine floating drug delivery system.A100 ml glass beaker was
modified by adding a side arm at the bottom of the beaker so that the beaker can hold
70 ml of 0.1 N HCL dissolution medium and allow collection of samples. It was
found that the drug release followed zero order kinetics in the proposed method115.
Koester, et al., (2004), investigated the release kinetics of carbamazepine either
complexed or physically mixed with beta cyclodextrin from
hydroxypropylmethylcellulose matrix tablets using different mathematical equations.
They found that weibull model was more useful for comparing the release profiles116.
Uhumwangho, et al., (2005) determined the effect of humidity on the disintregrant
property of α cellulose .It was found that moisture uptake affected the hardness and
disintegration times of the tablets to different degrees. The disintegration times of
tablets increased considerably following their exposure to moisture117.
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