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F R I D AY, O C T O B E R 1 9 , 2 0 0 7

Literature review

Literature Review
Papadimitriou Elpiniki. et al, (1993) investigated whether the faces of cylindrical compacts of HPMC were of
different nature to the edge. This was studied by coating the edges and faces of different compacts with paraffin,
in order to prevent water access. Results concluded that the faces and edges of the HPMC compacts behaved in an
identical manner. The axial relaxation must simply to the relief of stresses induced during compaction.
Talukdar, et al, (1993)63 evaluated xanthan gum as hydrophilic matrix for controlled release preparation.
Different parameters such as direct compression, wet granulation, gum concentration, surfactants etc. were
studied for their effect on drug release. Only gum concentration and ionic strength of the media were reported to
influence drug release.
Pham and Lee. et al, (1994)50 analyzed mechanisms of drug release from HPMC matrices and determined
associated kinetics of polymer swelling and dissolution. Their results showed that release of water-soluble
Katzhendler Ifat. et al, (1997) investigated influence of hydroxypropyl methycellolose (HPMC) on the crystal
habit properties of carbamazepine in sustained release matrix tablets and in aqueous solutions was investigated
using differential scanning calorimetry (DSC), X-ray powder diffraction and scanning electron microscopy
(SEM). Results suggested that HPMC inhibits the transformation of carbamazepine to carbamazepine dihydrate in
the gel layer of hydrate tablets and in aqueous solution s (depending on HPMC concentration), participates in its
crystallization process and induces amorphism of carbamazepine crystals.
Qiu Y. et al, (1997) developed a hydrophilic matrix system for extended oral delivery of zileuton and studied
effects of certain formulation, processing and dissolution variables on in vitro drug release. Result showed that
accelerated release was observed with increased agitation as well as in the dissolution media with higher
surfactant concentration and ionic strength.
Cox. et al, (1999)66 showed greater sustaining action of Xanthan gum than HPMC or karaya gum in the release of
S (+) - ibuprofen from matrix tablets prepared by wet granulation method.
Lee. et al, (1999)53 developed HPMC matrix tablets containing Melatonin aimed at oral delivery to the peptide.
They reported release rate to decrease with increase in polymer content.
Peh. et al, (2000)67 showed tablets with HPMC, XG & MCC to have pH independent release profiles. Drug
release could be sustained in predictable manner by modifying polymer content.
Boza A. et al, (2000) investigated the statistical optimization of sustained-release matrix tablets of lobenzarit
disodium salt (LDS) was performed using the central composite experiment design 23 for three independent
variables: the amount of polymer (Eudragit® RS-PO) AP, the total volume of granulation solvent VS, and the
amount of filler (microcrystalline cellulose) CE. Results concluded that response surfaces were performed from a
statistical mathematical model and optimal formulation obtained for the variables (AP = 15 mg, VS = 60 ml, and
CE = ).
Sasa Baumgartner. et al, (2000)25 investigated the development of floating matrix tablet to prolong the gastric
residence time, increase the drug bioavailability and diminish the side effects of drugs. Tablets containing HPMC,
drug and different additives were compressed. The investigation showed that tablet composition and mechanical
strength have the greatest influence on floating properties and drug release.
Carla Sanchez. et al, (2001) formulated Didanosine, into directly compressed monolythic matrices whose
excipients were mixtures at different ratios of a methacrylic resin (Eudragit RSPM) and an ethylcellulose (Ethocel
100), both water-insoluble and pH-independent polymers. The results showed the suitability of Eudragit–Ethocel
mixtures as matrix-forming material for didanosine sustained release formulations the tablet formulation.
Chebli C. Et al, (2001) Substituted amylose polymers were prepared by reacting amylose chains with a suitable
substituent such as 1,2-epoxypropanol (glycidol). Substituted amylose polymers are introduced as novel
excipients for controlled release of bioactive materials. Results showed that Matrix systems and dry-coated tablets
maintained their structure, and controlled the release of drugs showing no significant degradation of tablets by a-
Vidya S. et al, (2001)26 studied the in-situ interaction between drug and electrolytes such as calcium carbonate,
magnesium carbonate, sodium bi carbonate and sodium carbonate in different concentrations. The results shows
that swelling and gel formation in the presence of ionisable species within hydrophilic matrices provide an
alternative for controlled drug delivery from a simple monolithic system.
Paloma FRUTOS. et al, (2001) investigated to control the release of ac active agent is to disperse it in an inert
polymeric matrix. Result showed that the main factor was the hydrodynamic condition of rate of flow.
C. Sanjeev. et al, (2001) formulated the controlled release tablets of diclofenac by using matrix embedding
techniques, Membrane barrier techniques and both and Investigated the comparative evaluation. Result was
showed that increasing the proportion of ethyl cellulose extended the release of Diclofenac sodium. Ideal
controlled release formulation of DFs, a combination of both matrix embedding and membrane barrier tech. was
found to be a better proposition for extended release beyond 12 hrs.
Raza M.S. et al, (2002) studied sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl
acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a
dosage from that manifests desirable release profile and thorough adherence to official monographs. It was found
that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an
important role in the release of drug from HPMC containing tablets with a trend towards zero-commercial brands
were also undertaken for comparison and modulation of the experimental batches.
Vathiya Lingam. et al, (2002)31 investigated the possibility of using carbopol polymeric solution as granulating
agent by the fluid bed granulation process to select a suitable method of tabletting for sustaining the release of
ketoprofen for 12 hours.
Maggi L. et al, (2002)81 investigated chemical and physical stability of HPMC matrices containing Diltiazem
Hydrochloride after gamma Irradition. Result found that γ irradiation Induces chemical modification. In the
structure of the active agent and also of the hydrophilic polymer.
Silvina A. Bravo. et al, (2002) formulated the controlled release of diclofenac sodium with help of bipolymeric
hydrophilic matrices and investigated the release study. Result was showed the release of Diclofenac sodium was
influenced by the presence of M.C.C. and different concentration of starch and lactose. Compare the conventional
tablets release of model drug from HPMC matrix tablets was prolonged.
Agrawal. et al, (2003) studied the applicability of fine particle ethylcellulose (FPEC) to produce matrix tablets by
a wet granulation technique was evaluated. The effect of various formulation and process variables, such as FPEC
content, hardness of the tablet, and solubility of the drug, on the release of drug from these tablets was examined.
Results showed that drug release rate increase with an increase in the solubility of the drug. Model equations,
intended to olucidate the drug release mechanism, were fitted to the release data.
Tiwari B S. et at, (2003)54 studied the controlled release formulation of Tramodol Hydrochloride using different
hydrophilic and hydrophobic polymers.
Michael M. et al, (2003) determined the physicochemical properties and investigated the drug release mechanism
from ethyl cellulose (EC) matrix tablets prepared by either direct compression or hot-melt extrusion (HME) of
binary mixtures of water soluble drug (guaifenesin) and the polymer. Results showed that release rate was shown
to be dependent on the ethyl cellulose particle size, compaction force and extrusion temperature.
Vorapann Mahaguna. Et al, (2003) investigated the influence of hydroxypropyl methylcellulose (HPMC)
molecular weight on pharmacokinetic and pharmacodynamic parameters of controlled release formulations
containing alprazolam. Tablet formulations contained alprazolam, excipients, and either HPMC K4MP or HPMC
K100LVP. In vitro dissolution results predicted in vivo pharmacokinetic and pharmacodynamic results
irrespective of formulation or diet used in the controlled release tablet. The controlled release tablets were
bioequivalent and pharmacodynamically equivalent irrespective of the tablet formulation.
Manuel Tapia. et al. (2003) formulated sustained-release tablet of amoxicillin and studied in vitro dissolution
profile by utilizing a direct UV-absorption method. Results showed that release curves determined by UV-
absorption and obtained from tablets containing 1017 mg amoxicillin trihydrate and Carbopol 1917P NF in a
range from 180 to 680 mg showed increasing values of the exponent indicative of the release mechanism (n) and
decreasing release constant values (k) as the matrix polymer content increased.
Isa Odidi. et al, (2003) Invented a noval sustained release composition and method for making such a composition
of diclofenac and its pharmaceutically acceptable salts. Results showed for once daily administration provides
controlled and long lasting in vivo release.
Gohel Mukesh C. et al, (2003) investigated the impact of formulation factor on the properties of a 12h modified-
release formulation of varapamil HCl. A2[3] andthe influence of amount of Eudragit RS PO/RL PO (X[1], a
matrixing agent cum binder) and PEG 4000 (X[3]; channelling agent cum plasticizer. Formulations showed
slower drug release in alkaline medium (pH 7.2). Succinic acid and KH[2]PO[4] were incorporated in the matrix
in order to obtain pH independent drug release.
Hosseinali Tabandeh. et al, (2003)35 formulated sustained release matrix tablets of Aspirin with Ethyl cellulose,
Eudragit RS 100 and Eudragit S 100 and study the release profile and their sensitivity to tablet hardness. Results
showed that Ethyl cellulose with an amount as little as 10 percent in formulation the release profile is not sensitive
to change in hardness.
K. Raghuram Reddy. et al, (2003)34 developed once daily sustained release matrix tablet of nicorandil by using
hydrophobic material like ethanolic solution of ethylcellulose eudrigit RL 100, PVP along with hydrophilic
material HPMC and sodium alginate. The most successful formulation of study exhibited drug release in initial
hours and total release very close to theoretical profile.
Selim Reza. et al, (2003)83 studied comparative evaluation of plastic, hydrophobic and hydrophillic polymers as
matrices for controlled release drug delivery of Diltiazem hydrochloride. Results indicated that statistically
significant differences were found among the drug release profile from different classes of polymeric matrices.
Uday S Toti. et al, (2003)84 formulated modified guargum matrix tablet for controlled release of diltiazem
hydrochloride. Results showed that drug release was swelling controlled Initially, but at later stage it becomes
dissolution controlled in Ph 7.4.
Meena Rani. et al, (2003) formulated osmotic pump controlled release tablets of diclofenac sodium and
investigated biopharmaceutical evaluation. Result was showed that drug release was dependent on type and
thickness of coating membrane but independent on orifice size and static condition. Osmotic pump tablets
provided a prolonged and controlled release of diclofenac sodium.
Shahla Jamzad. et al, (2004) studied influence of water-soluble and insoluble excipients on dynamics of
hydration, front movement, erosion, and drug release from hydrophilic matrix tablets containing water-soluble
drug was studied. Tablets were manufactured by direct compression, and their un-constrained swelling behavior
and gel strength were assessed with a texture analyzer. It was concluded that unlike in conventional dosage forms
inclusion of excipients in hydrophilic controlled-release tablets containing water-soluble drugs should be carefully
analyzed as their various physico-chemical properties may havesignificant implications on swelling dynamics.
Addis Ababa. et al, (2004) evaluated a comparative in vivo bioavailability of a newly formulated sustained release
paracetamol peroral matrix tablets and a marketed conventional rapidly disintegrating paracetamol tablets was
carried out according to a two-period, two-treatment, two-sequence, randomised crossover design with a 4-day
washout period between the treatments using urinary drug excretion data. Concluded that the bioavailability was
not significantly different from that of the conventional tablets (P = 02701). Moreover, by using the sustained
release tablets, it was possible to prolong the elimination half-life of the drug from 2.589 h to 3.840 h.
Seppo Pohja. et al, (2004) investigated the effect of a high degree on substituion (DS) on starch acetate (SA) and
SA concentration on tablet properties. With propranolol hydrochloride (PH) as model drug. Results showed that
Macroscopic cracks were formed during dissolution, which increased are available for Fickian diffusion and
resulted in slow attenuation of the drug release rate.
Jaber Emami. et al, (2004)39 investigated the influence of hydrophilic materials on the matrix tablets of lithium
carbonate. Results showed that matrix tablets containing 15% carbopol exhibited suitable release kinetics and
uniform absorption characteristics.
Nkere K Ebube. et al, (2004)58 investigated the influence of hydrophilic non Ionic cellulose ether polymers on
sustained release of Acetaminophen tablets. Results showed that tablets with HPC and HPMC had slower drug
Verma M. et at, (2004)85 investigated release of diltiazem hydrochloride from hydrophilic matrices of
polyethylene oxide and carbopol. Result showed that polyethylene oxide was more mucoadhesive than carbopol.
Rani M. et al, (2004) formulated sustained matrix, osmotic matrix and osmotic pump tablet of diclofenac sodium
and comparative in vitro and in vivo evaluation. In vivo results indicated prolonged blood level with delayed peak
and improved bioavailability for fabricated tablets compared to commercial tablets. It was concluded that osmotic
matrix and osmotic pump tablets could provide more prolonged controlled and gastrointestinal environmental
Independent DS release that may result in therapeutic efficacy.
Nie SF. et al, (2005) studied the erosion behaviour during dissolution of matrices using different molecular weight
polyethylene oxide (PEO) as hydrophilic polymer. It was concluded that a good candidate of hydrophilic polymer
and appeared to have great potential for controlled release applications.
Mashura Asharafi. et al, (2005)68 studied in vitro release of Metformin hydrochloride from matrix tablets
containing Xanthan gum as hydrophilic rate regarding polymel. Results indicated that higher proportion of
Xanthan gum, slow release of metformin hydrochloride obtained.
Ayhan Savaser. et al, (2005) investigated the effects of formulation variables on the release profile of diclofenac
sodium (DS) hydroxpropylmethyl cellulose (HPMC) and chitosan matrix tablets were studied. DS tablets were
prepared by wet granulation and direct compression methods and different ratios of HPMC and chitosan were
used. In vitro studies showed that 20% HPMC contained SR formulation with direct (dry) compression method is
the optimum formulation due to its better targeting profile in terms of release. This formulation also exhibited the
best-fitted formulation into the zero order kinetics.
Xiaoqiang Xu. et al, (2005) 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. Hydroxypropyl methylcellulose K4M and Carbopol 971P NF were used in
formulating the hydrogel drug delivery system. Results showed 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 tablet.
Ferrero. et al, (2005) formulated directly compressed theophylline tablets, containing commercial xanthan (X)
(Keltrol and a highly hydrophillic galactomannan (G) from the seeds of Mimosa scabrella (a brazilian leguminous
tree called bractinga) as release-controlling agents. Results showed that the drug release decreased with the
increase of polymer concentration and all formulations at 25% w/w of gums showed excessive sustained release
Lourdes Ochoa. et al, (2005) formulated the theophylline sustained release matrix tablets based on the
combination of hysroxypropyl methycellulose (HPMC K4M and K100M) and different meltable binders by melt
granulation in a high-shear mixer. The results suggested that melt granulation could be an easy and fast method to
formulate sustained release tablets.
Abdul Khalik Molla Md. et al, (2005)40 investigated rate controlled release of Naproxem from HPMC based
sustained release dosage form. Results showed that when the hydrophilic part of the combination was increased,
the release rate of NP was also increased.
Ishrat Nimmi. et al, (2005)41 studied the effect of electrolytes on release of Diclofenac sodium from agarose
beads. Result showed that increasing the polymer load decreased the rate and extent of drug release due to
increased thickness and reduced the porosity of the system.
Tanaka N. et al, (2005)42 formulated disintegration controlled matrix tablet (DCMT) with solid dispersion
granules of Nivadipine. Results showed that DCMT was one of the promising sustained release system by
applying solid dispersion for the poorly water soluble drugs.
Khullar. et al, (2005)65 showed swelling in guar gum matrices to be affected by drug concentration and viscosity
grade of polymer. They reported inverse relationship between drug concentration and matrix swelling.
Saul Borodkin. et al, (2006) Investigated release of methapyrilene, pentobarbital, and salicylic acid dispersed in
films composed of different ratios of hydroxypropyl cellulose and polyvinyl acetate The results showed that drug
release follows a diffusion-controlled matrix model, where the qualtity released per unit area is proportional to the
square root of time.
Chavanpatil MD. et al, (2006) formulated a new gastroretentive sustained release delivery system with floating,
swellable and bioadhesive properties. Polymers like psyllium husk, HPMC K100M and a swelling agent,
crosspovidone. Concluded in vitro drug release followed Higuchi kinetics and the drug release mechanism was
found to be of anomalous or non-Fickian type and high water uptake leading to higher swelling of the tablet
supported the anomalous release mechanism of ofloxacin.
Siepe S. et al, (2006) investigated pH modifiers as a commonly used strategy to enhance the dissolution rate of
weakly basic drugs from sustained release solid dosage forms. It was concluded that Fumaric and citric acid
reduced the pH(M) to equal extents in the initial phase. With the progress of hydration, the more soluble cirtic
acid diffused out from the tablet resulting in an increase in pH(M), originating at the outer layers.
Shoaib M.H. et al, (2006) developed a once-daily sustained release matrix tablet of ibuprofen using
hydroxypropyl methylcellulose (HPMC) as release controlling factor and to evaluate drug release parameters as
per various release kinetic models. Results showed that drug release data fit well to the Higuchi expression. Drug
release mechanism was found as a complex mixture of diffusion, swelling and erosion.
Gil E.C. et al, (2006) investigated sustained-release matrix tablets of racemic PPL were determined and compared
with the United States Pharmacopeia (USP) tolerance specifications. Results suggested that the dissolution profile
of the present two sustained release oral dosage forms are similar. Higuchi (diffusion) and Hixon-Crowell
(erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established.
Maki R. et al, (2006) studied controlled release tablets of N-acetyl-d glucosamine (NAG), maltose monohydrate
and maltopentaose by using hydrophobic matrix formers starch acetate (SA) and ethyl cellulose (EC). The
investigation showed that both SA and EC matrices were found to represent suitable controlled oral delivery
vehicles for saccharides.
Lopes CM. et al, (2006) formulated mini tablets containing either hydroxypropylmethylecellulose (HPMC) or
ethylcellulose (EC) as release controlling agent. Results showed that different grades of viscosity of HPMC did
not modify ibuprofen release. EC formulations, the contribution of diffusion was predominant in the ibuprofen
release process.
Mhammad Khan Sarfraz. et al, (2006) investigated the low viscosity grades of hydroxypropylmethyl cellulose
(HPMC) and ethyl cellulose (EC) in sustaining the release of water insoluble drug, naproxen from the matrix
tablets. Results concluded that EC significantly reduced the rate of drug release compared to HPMC in 12 hour
testing time. But no significant difference was observed in the release profile of matrix tablets made by higher
percentages of EC.
Corvi Mora P. et al, (2006) formulated the sustained-release matrix-tablets of dehydroepiandrosterone (DHEA) as
ternary complex with a-cyclodextrin and glycine (c-DHEA) by direct compression with suitable excipients.
Results showed that the drug release profile from the most effective matrix-tablet formulation of c-DHEA allowed
achievement of a more than 6-fold increase in the drug amount released within 24 h in comparison with the same
formulation containing the simple physical mixtures of DHEA, a-cyclodextrin and glycine.
Morkhade D. et al, (2006) Formulated sustained matrix tablet of diclofeual-sodium Modal drug with natural-gum
copal and gum damar as noval sustained release matrix forning material by wet-granualtion method. Result
showed that both the gums produce matrix tablet with good strength and acceptable pharmacotechnical properties
and posses substantial matrix forming property that could be used for sustained drug delivery.
Senapati MK. et al, (2006)43 investigated the influence of Karaya gum and Guargum on pharmacokinetic and
pharmacodynamic parameters of controlled release formulation containing phenyl propanolamine. Results
indicated that the tablets with Karyagum exhibited greater swelling indices them with guargum so combination of
karyagum and guargum exhibited more sustained release than individual gum.
Varshosaz J. et al, (2006)44 investigated the influence of natural gum and cellulose derivatives on sustained
matrix tablets of Metoprolol. Results showed that natural gums are suitable for production of sustained release
tablets of Metoprolol.
Yeole P G. et al, (2006)69 formulated Xanthan gum based sustained release matrix tablets of Diclofenac sodium.
Result showed that Xanthan gum is an effective matrix former, to extend the release of diclofenac sodium.
Varshosaz J. et al, (2006)70 formulated sustained release matrix tablets of Tramadol hydrochloride by using
natural gum. Result showed that tablets with xanthan gum had the highest mean dissolution time (MDT).
Mamoru Fukuda. et al, (2006)71 formulated sustain releasle hot-melt extruded tablets containing chitosan and
Xanthan gum. Result showed that HME tablets containing both chitosan and Xanthan gum had no significant
change in drug release rate.
Atul Kuksal. et al, (2006)76 formulated the extended release matrix tablets of Zidovudine with combination of
hydrophilic and hydrophobic matrix formers and investigated the in vitro and in vivo evaluation. Results shows
that HP Cellulose preparation was able to sustain the drug release.
Basak Sc. et al, (2006)61 investigated the release behaviour of sustained release Ambroxol hydrochloride HPMC
matrix tablet. Result showed that a decreased in release kinetics of the drug was observed on increasing polymer
Carla M Lopes. et al, (2006)60 formulated direct compressible mini matix tablet containing either HPMC or ethyl
cellulose as release controlling agent. Results found that in EC formulation the contribution of diffusion was
predominant in ibuprofen release process. EC produces greater sustaining effect then HPMC.
Chopra S. et al, (2007) studied an optimized sustained release dosage form of an anti-hypertensive agent, losartan
potassium, using response surface methodology by employing a 3-factor, 3-level Box-Behnken statistical design.
Tablets showed an initial burst release preceding a more gradual sustained release phase following a non-fickian
diffusion process. The Box-Behnken experimental design facilitated the formulation and optimization of sustained
release hydrophilic matrix systems of losartan potassium.
Tanaka Y. et al, (2007) evaluated the application of a hydrophilic matrix tablet capable of polyion complex (PIC-
tablet) to a controlled-release release device for highly water-soluble drugs. The PIC-tablet was prepared from a
mixture of dextran sulfate and dextran chloride and diltiazem hydrochloride was used as a model drug. Results
showed that the PIC-tablet is a promising device for oral controlled release delivery of water-soluble drugs with
good micelle-forming ability.
Phaechamud T. et al, (2007) formulated Sustain-release tablets of propranolol HCL by direct compression using
chitosan and xanthan gum as matrix materials. Results showed that decreased rate of polymer dissolution
resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to
ionic interaction between chitosan and xanthan gum. This suggested that the utilization of chitosan and xanthan
gum could give rise to layered matrix tablet exhibiting sustained drug release.
Kafedjiiski K. et al, (2007) studied synthesize and characterize a novel hyaluronic acid-cysteine ethyl ester (HA-
Cys) conjugate providing improved mucoadhesive properties and a significantly lowered biodegradation rate.
Results showed that novel thiolated polymer seems to represent a promising multifunctional excipient for the
development of various drug delivery systems.
Nabais T. et al, (2007) formulated high-amylose corn starch, that contains 70% of amylose chains and 30% of
amylopectin, has been used to obtain substituted amylose (SA) polymers. It shows that a compressed blend of
HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained release tablet with
improved integrity for oral administration and in-vivo studies demonstrate extended drug absorption.
Thawatchai Phaechamud. et al, (2007) formulated sustained-release tablets of propranolon HCl by direct
compression using chitosan and xanthan gum as matrix materials. Results showed that the utilization of chitozan
and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.