2. REVIEW OF LITERATURE - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/28939/11/11_chapter...

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



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.



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.



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.



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.



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.



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.



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.



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.



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.



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%



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.



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



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



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



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



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



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.



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



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.



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.



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



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



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.



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.



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.

2. REVIEW OF LITERATURE - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/28939/11/11_chapter...

Documents

Transcript of 2. REVIEW OF LITERATURE - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/28939/11/11_chapter...