2. review of literature 2.1. literature reviewed on...

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


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


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.


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.


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


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


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.


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


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.


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.


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


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


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.


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


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


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.


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


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).


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.


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


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.

2. review of literature 2.1. literature reviewed on...

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