Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
Contents lists available at ScienceDirect
H O S T E D BY
Future Journal of Pharmaceutical Sciences
journal homepage: http://www.journals.elsevier.com/future-journal-ofpharmaceutical-sciences/
Pharmaceutical significance of Eudragit: A review
Ch. Niranjan Patra a, *, Richa Priya a, Suryakanta Swain b, Goutam Kumar Jena a,
Kahnu Charan Panigrahi a, Debashish Ghose a
a
b
Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, India
SIMS College of Pharmacy, Guntur, India
a r t i c l e i n f o
Article history:
Received 19 September 2016
Accepted 13 February 2017
Available online 9 March 2017
1. Introduction
The Eudragit® range of polymers, like the versatile acrylic material Plexiglas (introduced in 1933), grew out of Dr. Rohm’s deep
knowledge of acrylic acid and its derivatives. In the year 1954 first
two polymers Eudragit L and Eudragit S for enteric coating were
launched. It offered a synthetic polymer for film-coating of
improved quality than materials such as sugar and shellac. Eudragit
based products for rapidly disintegrating and sustained release
coatings were added during the 1960s, expanding the widening
potential applications considerably. The introduction of aqueous
polymer dispersion forms of Eudragit in 1972 was a major milestone, making the process of coating easier, safer, more versatile
and economical. With the development of various grades of
Eudragit, it became possible to handle many aspects of formulation
development such as film coating, granulation, direct compression,
melt extrusion and mastery of technologies to engineer immediate
or sustained release, as well as GI targeting, enteric coatings, pulsed
release and transdermal formulations. Hence Eudragit a versatile
polymer for drug delivery was selected for extensive review.
Polymethacrylates are synthetic cationic and anionic polymers
of dimethylaminoethyl methacrylates, methacrylic acid, and
methacrylic acid esters in varying ratios. Several types are
commercially available and may be obtained as the dry powder,
aqueous dispersion, organic solution [1]. The most commonly used
organic phase used was a (60:40) mixture of acetone and propan-2ol. Polymethacrylates are primarily used as film-coating agents in
* Corresponding author. Roland Institute of Pharmaceutical Sciences, Berhampur,
760010, Ganjam, Odisha, India.
E-mail address: drniranjanrips@gmail.com (Ch.N. Patra).
Peer review under responsibility of Future University.
tablet and capsule dosage forms. Films of different solubility can be
produced by using different polymer grades. Table 1 outlines the
solubility profile of each grade of Eudragit. Broadly polymethacrylates are used as film former, tablet binder and tablet
diluents. Apart from the above applications, recent studies revealed
that polymethacrylates have got widespread applications in
-vis taste masking, better permeation across skin,
formulation vis-a
intestinal epithelium and corneal permeation, dissolution
enhancement, bioavailability enhancement, enteric coating, sustain
release, radioprotection, pH dependent release, colon targeting etc.
Therefore polymethacrylates play a pivotal role in formulation and
development of different type of dosage forms with versatile applications. Hence the objective of the present manuscript is to make
a compilation review on research publications and patents on
various applications of Eudragit.
Polymethacrylates are known with various synonyms such as
Acryl-EZE, Acryl-EZE MP, Eastacryl 30D; Eudragit; Kollicoat MAE 30
D; Kollicoat MAE 30 DP; polymeric methacrylates. This present
review focused on various grades of Eudragit which is a trademark
of GmbH & Co.K.G Darmastadt in Germany, first marketed in 1950s.
polymerization of acrylic & methacrylic acids or their esters was
adopted to obtain Eudragit e.g. butyl ester or dimethylaminoethyl
ester. Chemical structure of Eudragit is shown in Fig. 1. Eudragit was
included in USPNF, BP and PhEur. Dry powder polymer forms are
stable at temperatures less than 30 C. Dry powders are stable for at
least 3 years if stored in a tightly closed container at less than 30 C.
Dispersions should be stored at temperatures between 5 and 25 C
and are stable for at least 18 months. Eudragits are generally
regarded as nontoxic and nonirritant materials. A daily intake of
2 mg/kg body-weight in humans is regarded as essentially safe. It is
included in the FDA Inactive Ingredients Guide (oral capsules and
tablets), nonparenteral medicines licensed in the UK, Canadian list
of acceptable nonmedicinal ingredients.
2. Literature review
A comprehensive review of literature is discussed in length
highlighting their applications. Research articles reported for each
grade are enlisted in tabular form. Some of those articles are discussed critically with special reference to eudragit.
http://dx.doi.org/10.1016/j.fjps.2017.02.001
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Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
Table 1
Tabulation for solubility of various grades of Eudragit [1].
Grades of Eudragit
Recommended solvents
Solubility/Permeability
Eudragit E12,5,
Eudragit E100,
Eudragit EPO
Eudragit L 100-55,
Eudragit L 30 D-55,
Eastacryl 30D,
Kollicoat 30D
Kollicoat 30DP
Acryl EZE
Acryl EZE MP
Eudragit L-12.5P,
Eudragit L-12.5,
Eudragit L 100
Eudragit S 12.5P,
Eudragit S 12.5,
Eudragit S 100
Eudragit FS 30D
Eudragit RL12.5,
Eudragit RL100,
Eudragit RD 100
Eudragit RL PO
Eudragit RL 30D
Eudragit RS 12.5
Eudragit RS 100
Eudragit RS PO
Eudragit RS 30D
Eudragit NE 30D,
Eudragit NE 40D
Acetone, alcohol
Soluble in gastric fluid to pH 5
Acetone, alcohol for L100-55
Water
Soluble in intestinal fluid from pH 5.5
Acetone, alcohol
Soluble in intestinal fluid from pH 6
Acetone, alcohol
Soluble in intestinal fluid from pH 7
Water
Acetone, alcohol
High permeability
Water
Acetone, alcohol
Low permeability
Water
Water
Swellable, permeable
2.1. Eudragit E100, E12,5 and EPO
In this series there are three different grades of Eudragit vis-avis Eudragit E100, E12,5 and EPO. All the three are cationic copolymer based on dimethylaminoethyl methacrylate, butylmethacrylate and methyl methacrylate. Chemically they are known as
poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylateco-methyl methacrylate. They possess a molecular weight of
approximately (47,000 g/mole), alkali value (180 mg KOH/g of
polymer) and glass transition temperature (48 C). They are soluble
in gastric pH up to 5.0. Low viscosity, high pigment binding capacity, good adhesion and low polymer weight gain are the
Fig. 1. Chemical structure of Eudragit, For Eudragit E: R1, R3]CH3, R2]
CH2CH2N(CH3)2, R4]CH3, C4H9 For Eudragit L and Eudragit S: R1, R3]CH3, R2]H,
R4]CH3 For Eudragit FS: R1]H, R2]H, CH3, R3]CH3, R4]CH3 For Eudragit RL and
Eudragit RS: R1]H, CH3, R2]CH3, C2H3, R3]CH3, R4]CH2CH2N(CH3)þ3Cl For
Eudragit NE 30 D and Eudragit NE 40 D: R1, R3]H, CH3, R2, R4]CH3, C2H3 For AcrylEZE and Acryl-EZE MP; Eudragit L 30 D-55 and Eudragit L 100-55, Eastacryl 30 D,
Kllicoat MAE 30D, and Kollicoat MAE 30 DP: R1, R3]H, CH3, R2]H, R4]CH3, C2H3.
characteristic properties of Eudragit E series. They are commonly
used in film coating, odour and taste masking, moisture and light
protection. They differ from each other in terms of their physical
appearance. Eudragit S100 is available in the form of granules
which consists of colourless to yellow tinged granules with a
characteristic amine like odour. Eudragit E 12,5 is available in the
form of organic solution which is a light yellow liquid of low viscosity, clear to slightly cloudy with characteristic odour of solvent.
Eudragit EPO is available in the form of powder with a characteristic amine like odour.
A current literature review on Eudragit E 100 reveals that it has
been used in nanoparticles, microparticles, transdermal spray,
ophthalmic solution, floating drug delivery system etc as shown in
Table 2. Quinteros et al. [2] proposed a novel ophthalmic solution
based on the ionic complexation between Eudragit E 100 and
flurbiprofen. Dispersion of the drug and Eudragit complex in 0.9%
w/v sodium chloride (NaCl) increased flurbiprofen release through
an ionic exchange, providing a controlled release and more effective corneal permeation without any irritation. Paradkar et al. [3]
formulated clotrimazole transdermal spray using different ratios
of ethanol and acetone and various grades of eudragit and ethyl
cellulose. The following parameters like viscosity, drying time,
stickiness, appearance, integrity on skin and water washability
were evaluated. The desired criteria was achieved by using Eudragit
E100 and mixture of ethanol and acetone (80:20). The optimized
formulation exhibited improved drug permeation through the rat
skin and improved antifungal efficacy as evidenced from higher
zone of inhibition. Dominguez et al., [4] prepared triclosan nanoparticles suspension by the emulsification-diffusion by solvent
displacement method, using Eudragit® E 100 as polymer. Triclosan
was molecularly dispersed in the nanoparticle batches containing
triclosan. Nanoparticles exhibited higher permeation compared to
solutions and creams. Patil et al. [5] explored the application of
Eudragit E 100 as taste masking agent in orally disintegrating tablet
of tramadol hydrochloride. The results demonstrated successful
masking of bitter taste.
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
35
Table 2
Reported literature on Eudragit E 100, E 12,5 and EPO.
*
Drug name
Dosage form/delivery system
Method of Preparation
Applications
References
Eudragit E 100
Flurbiprofen
Opthalmic aqueous solution
Ionic complexation
[2]
Clotrimazole
Triclosan
Transdermal spray
Nanoparticles
Tramadol Hydrochloride
Carvidilol
Orally disintegrating tablet
Nanoparticles
Eutectic mixture
Emulsification-diffusion by solvent
displacement method
Mass extrusion technique
Nanoprecipitation
Constant rate of delivery and improved
permeation
Improved drug transport across the skin
Improved drug delivery
[5]
[10]
Ranitidine hydrochloride
Floating microspheres
Solvent evaporation method
Bitter taste masking
Improved therapeutic efficacy (Faster
dissolution)
Improved absorption and
bioavailability
[3]
[4]
[11]
Eudragit E 12,5
*
Eudragit EPO
Clindamycin HCl
*
*
*
*
Oral disintegrating tablet
Improved pediatric and geriatric
patient compliance by taste masking.
[6]
Osthole
Solid dispersion
Drug coated to MCC beads followed by
coating of eudragit EPO suspension
followed by compression
Hot-melt extrusion
[12]
Atorvastatin
Bifendate
Meloxicam
Amorphous solid dispersions
compressed to orally disintegrating
tablet
solid dispersions
Nanoparticles
Hot-melt extrusion
Nanoprecipitation method
Andrographolide
pH sensitive nanoparticle suspension
Nanoprecipitation technique
Aciclovir and Minoxidil
liposomes
High-pressure homogenization
Diclofenac sodium and
Theophylline
Polycomplex matrices
Interpolyelectrolyte complexes (IPEC)
between countercharged polymers
Improved dissolution rate and
bioavailability
Improved bioavailability by increasing
its gastric solubility in a stable oral
disintegration tablet
Enhanced bioavailability
Improved anti-inflammatory activity
compared to suspension.
Improved the oral bioavailability with
shorter Tmax
Cationic polymers had a stabilising
effect
Considerable pH-sensitive swelling in
acidic and neutral media
Direct compression
[7]
[13]
[8]
[14]
[9]
[15]
No literature found.
No literature was found for Eudragit 12,5 in pubmed indexed
journals. An extensive review on applications of Eudragit EPO
revealed that it can be used in formulations such as solid dispersions, orally disintegrating tablets, nanoparticles, nanosuspensions,
stabilization of liposomes, superior moisture protection for solid
dosage forms etc are shown in Table 2. Cantor et al. [6] explored
taste masking potential of Eudragit EPO by formulating orally disintegrating tablets of clindamycin HCl. Coating of Clindamycin HCl
with Eudragit EPO suspension subsequent compression into tablet
showed improved pediatric and geriatric patient compliance for
clindamycin. Salmani et al. [7] investigated solubility and
bioavailability enhancement potential of orally disintegrating
tablet compressed from solid dispersions of atrovastatin with
Eudragit EPO. Solid dispersions significantly improved the dissolution of atrovastatin. In vivo study showed. 434% more bioavailability than plain atrovastatin tablets. Khachane et al. [8]
investigated the potential of Eudragit EPO nanoparticles in
improving therapeutic efficacy of meloxicam and compared with
conventional meloxicam suspension. Meloxicam loaded eudragit
EPO nanoparticles were prepared by nanoprecipitation method.
Improved anti-inflammatory activity with lesser ulcerogenicity was
observes with optimized nanoparticles. Hasanovic et al. [9]
improved physicochemical properties of liposomes by using
cationic polymer i.e. chitosan and Eudragit EPO. 1,2-Dipalmitoyl-snglycero-3-phosphocholine (DPPC) liposomes were prepared by
high-pressure homogenization. Zeta potential and mean particle
size revealed that the polymeric liposomes are stable. In the presence of the drugs (acyclovir and minoxidil), the polymeric liposomes still showed constant particle size and zeta potential.
Moreover, the coating of liposomes with chitosan or Eudragit EPO
led to higher skin diffusion for both drugs. The interaction between
the skin (negatively charged surface) and liposomes (positively
charged) was the probable reason for increased skin diffusion.
2.2. Eudragit L 100 and 12,5
Eudragit L 100 and L 12,5 are anionic copolymers based methacrylic acid and methyl methacrylic acid. Both the polymers possess
similar molecular weight 1,25,000 g/mol, acid value 315 mg KOH/g
of polymer and glass transition temperature greater than 150 C.
Targeted drug release area for both the polymer is jejunum and
dissolves at pH above 6. They are used for effective and stable
coatings with fast dissolution in the upper bowel, granulation of
drug substance in powder form for controlled release, site specific
drug delivery in intestine etc. The only difference between these
two grades is Eudragit L 100 is available in the form of solid powder
with a faint characteristic odour whereas Eudragit 12,5 is a organic
solution which is colourless and clear to slightly cloudy liquid with
the characteristic odour of isopropyl alcohol.
A current review on Eudragit L 100 exhibits that it has been used
in various formulations such as microspheres, microsponges,
nanoparticles, liposomes, lipotomes, tablets etc for different applications such as enteric coating, sustain release, insulin permeation, bioavailability enhancement etc as shown in Table 3. Li et al.
[16] filled self nanoemulsifying drug delivery systems (SNEEDS) of
insulin into Eudragit L100 based enteric coated capsules. A pHdependent insulin release profile was observed. In healthy fasted
rats, administration of SNEDDS produced a 2.7 and 3.4 fold
enhancement in the relative bioavailability and glucose reduction,
respectively. This study showed enhanced oral absorption and efficacy of insulin. Sareen et al. 2014 [17] evaluated colon specific
drug delivery potential of Eudragit L100 by formulating microponges of curcumin. Release studies revealed that microsponges
prevented the premature release of curcumin in upper GIT and
specifically released the drug at colonic pH. Microsponges with
Eudragit L 100 can be used as a promising drug delivery system for
treatment of ulcerative colitis. Hosny et al. [18] made a novel
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Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
approach to overcome barriers for the treatment of osteoporosis by
formulating enteric-coated alendronate sodium (ALS) nanoliposomes. Optimized nanoliposome coated with Eudragit L 100
successfully resisted the release of ALS in acidic environments and
enhanced the bioavailability in rabbits. Wilson et al., [19] prepared
and evaluated sustain release enteric coated tablets of pantoprazole. The prepared tablets were dip coated using an enteric
coating polymer such as cellulose acetate phthalate and eudragit
L100. The study revealed that the prepared tablets were able to
sustain drug release into the intestine. The enteric coated pantoprazole tablets significantly reduced ulcer formation. No literature found for Eudragit 12,5 in pubmed indexed journals.
2.3. Eudragit L 30 D 55 and L 100-55
Eudragit L 30 D 55 is the aqueous dispersion of anionic polymers
with methacrylic acid as a functional group. It is a low viscosity
liquid of white color with faint characteristic odour. It is obtainable
in the form of aqueous dispersion (30%) whereas eudragit L 100-55
is an anionic copolymer based on methacrylic acid and ethyl
acrylate. It is a white powder with a faint characteristic odour. Both
grades of Eudragit have molecular weight 3,20,000 g/mol, acid
value 315 mg KOH/g of polymer and glass transition temperature
110 C. Targeted drug release area for both is duodenum and they
dissolve at pH of 5.5. Both the polymers are used for effective and
stable coating with fast dissolution in the upper bowel, controlled
release, site specific drug delivery in intestine etc.
An up to date literature review on the applications of Eudragit L
30 D 55 polymer suggests that it has been used in the formulation
of microspheres, microparticles, film coated tablets, pellets, transdermal film, enteric coating etc with various objectives such as
improving bioavailability, drug release at intestine, sustain release
etc as shown in Table 4. Nair et al. [23] evaluated four different
polymers such as Eudragit L-30 D-55, hydroxy propyl methylcellulose phthalate, cellulose acetate phthalate and Acryl-EZE® by
formulating enteric coated tablets of esomeprazole magnesium
trihydrate. Tablets with 5% weight gain, failed disintegration test in
0.1 N HCl media. It was observed that 8% w/w enteric coating
passed disintegration test. Methacrylic polymers (Eudragit L 30 D
55 and Acryl EZE) exhibited better dissolution rate than the cellulose polymers. Naseem et al. [24] designed transdermal films of
tenoxicam with Eudragit L 30D55 along with permeation enhancers like polyethylene glycol (PEG) and propylene glycol (PG). A
drag effect was observed due to interaction between tenoxicam and
Eudragit L30D-55 leading to a delay of the tenoxicam release.
Bendas et al. [25] attempted extrusion-spheronization followed by
spray coating for leaky enteric-coated pellets of ranitidine HCl.
Pellets were prepared using Eudragit L 30 D-55, combined with
soluble lactose, PEG 8000 and surfactants (span 60 (hydrophobic)
or tween 80 (hydrophilic). Leaky enteric coated pellets allowed the
release of some amount of drug in gastric fluid.
Similarly an extensive up to date review on the polymer
Eudragit L100-55 suggests that this can be used in the formulations
for various applications such as pH responsive drug release, taste
masking, drug release at intestine, radioprotection etc as shown in
Table 4. Lotikar et al. [26] designed multiparticulate dosage form of
ketoprofen by extrusion and spheronization technique. It was
based on pH-responsive dual pulse release concept. Pellets were
coated with pH sensitive Eudragit L 100-55 and Eudragit S 100 for
site-specific drug release with lag time. The dual pulse release after
a lag time of 2 and 5 h was observed. The first dose release was
established in pH 1.2 for a period of 2 h, followed by pH 6.8. The
second dose pellets were passed through pH 1.2, pH 6.8 followed by
pH 7.5 for the rest of the study. The authors concluded that multiparticulate dosage form of ketoprofen was able to relieve circadian symptoms of rheumatoid arthritis during midnight and early
morning. Maniruzzaman et al. [27] prepared extrudes of cationic
model drug propranolol HCl by extrusion and spheronization
technique with the anionic polymers Eudragit L100 and Eudragit
L100-55. Taste masking was determined by using e tongues.
Intermolecular interactions as the mechanism of successful taste
masking was ascertained from FT-IR spectroscopy and NMR
studies. Aguilar et al. [28] used polyurethane and Eudragit® L10055 as nanofiber by belectrospinning technique. The composite
mat has adequate mechanical properties and in vitro cell biocompatibility indicating that the material can be used for drug eluting
stent cover application. De Barros et al. [29] designed a laminated
polymer film formulation for enteric delivery of live vaccine and
probiotic bacteria. Eudragit L 100-55 based polymeric laminate
successfully protected dried probiotic or vaccine live bacterial cells
from SGF for 2 h, and subsequently released all viable cells within
60 min of transfer into simulated intestinal fluid.
2.4. Eudragit S (S-100, 12,5 and FS 30 D)
Eudragit S 100 and S 12,5 are anionic copolymers based on
methacrylic acid and methyl methacrylate. Eudragit S100 is solid
substance in the form of white powder with a faint characteristic
odour. Eudragit S12,5 is a colourless and clear to slightly cloudy
liquid with characteristic odour of isopropyl alcohol. Both grades
Table 3
Reported literature on Eudragit L 100 and 12,5.
Drug name
Dosage form/delivery system
Oral insulin
Combination of Self nanoemulsifying DDS In-situ emulsification
& enteric coated capsules
Microsponge for colon targeting
Quasi emulsion solvent diffusion
method
Lyophilised Lipotomes filled into enteric Thin film hydration technique
coated capsules.
floating alginate beads combined with the Ionic cross linking and solid
solid dispersion
dispersion technique
Enteric-coated nanoliposomes
Nanotechnology
Curcumin
Lacidipine
Dipyridamole
Alendronate
sodium (ALS)
Pantoprazole
Delayed release tablets
Insulin
Thiolated eudragit based nanoparticles
with reduced glutathione.
Eudragit L 12,5
*
*
*
No literature found.
Method of Preparation
Application
Reference
[16]
Wet granulation method
followed by enteric coating
Nanotechnology
Enhancing the oral absorption and efficacy of insulin and
eudragit L 100 as a enteric polymer.
Eudragit L 100 prevented the premature release of curcumin in
upper GIT.
Lipotomes enhanced oral bioavailability and Eudragit L 100 as a
enteric polymer.
Prolonged stomach retention time due to CaCO3 and modified
drug release due to Eudragit L100 and RLPO.
Resist the release of ALS in acidic environments and enhanced
the bioavailability
Sustained release in intestine and significant reduction in ulcer
formation
Facilitate insulin permeation through the intestinal epithelium.
*
*
[17]
[20]
[21]
[18]
[19]
[22]
*
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
37
Table 4
Reported literature on Eudragit L30 D-55 and L 100-55.
Drug name
Dosage form/delivery
system
Eudragit L 30D-55
Oral Chlorea
Microparticles
vaccine
Tenoxicam
Transdermal self-adhesive
films
Enteric coated tablet
Esomeprazole
magnesium
trihydrate
Tamsulosin
Controlled-release
hydrochloride
capsule
Ranitidine
leaky enteric-coated
hydrochloride
pellets
Diclofenac sodium
Enteric coated pellets
compressed into tablets
Microsphere
Mycoplasma
hyopneumoniae
oral vaccine
Eudargit L 100e55
Ketoprofen
pH-responsive dual pulse
multiparticulate dosage
form
Propranolol HCl
Taste mask formulation
Amifostine
Enteric microcapsules
Omeprazole
Nanoparticles
Gemcitabine
Domperidone
Paclitaxel
Live bacterial cells
as attenuated
vaccines
Cinnarizine
Insulin
Method
Application
References
Spray dried technique
An approach to a cold chain free and effective oral cholera vaccine.
[30]
Casting evaporation
technique
Coating
Sustain drug release
[24]
Better dissolution & stable for a period of 3 months.
[23]
Extrusion/
Controlled release
spheronization method
Maintain or increase the bioavailability of drugs that have a window of absorption
Extrusionspheronization followed
by spray coating
Fluidized-bed coating
The mixture of Eudragit NE30D and Eudragit L30D-55 could be used to prepare
enteric pellets.
Co spray drying
Oral microspheres vaccine prepared by a co-spray drying method can provide
effective protection against M M. hyopneumoniae infection in pigs.
Extrusionspheronization & Fluid
bed coating.
Hot melt extrusion
(Single screw)
Spray drying technique
Ultrasonic dispersion
and diffusion
solidification
Enteric Microparticles
Double emulsion
method
Oral disintegrating tablet Direct compression
method
Nanofiber composite mat Electrospinning process
Polymer film laminate
Film casting
Microparticles
Enteric nanoparticles
Coacervation technique
Complex coacervation
method
[31]
[25]
[32]
[33]
To relieve circadian symptoms of rheumatoid arthritis during midnight and early [26]
morning
Drug polymer intermolecular interactions as the mechanism of successful taste
[27]
masking.
Oral administration of amifostine microcapsules provided effective radioprotection [34]
compared to the bulk drug.
Nanoparticles showed a strong pH-sensitive release in vitro.
[35]
Oral absorption could be increased with mucoadhesive polymer
[36]
Fast and pH-dependent release
[37]
pH dependent release of paclitaxel on duodenal stent cover application.
[28]
Eudragit alone successfully protected dried probiotic or vaccine LBC from SGF for [29]
2 h, and subsequently released all viable cells within 60 min of transfer into SIF.
pH responsive drug release
[38]
Complex coacervation process using chitosan and Eudragit L100-55 polymers may [39]
provide a useful approach for entrapment of hydrophilic polypeptides without
affecting their conformation.
have molecular weight, acid value and glass transition temperature
approximately 125,000 g/mol, 190 mg KOH/g polymer and >150 C
respectively. Eudragit S 100 is available in the form of powder.
Eudragit S 12,5 is available in the form of organic solution (12.5%).
Both grades dissolve at pH 7.0 and used for colon targeted drug
delivery.
Eudragit FS 30D is a milky white liquid of low viscosity with a
faint characteristic odour. It is the aqueous dispersion of an anionic
copolymer based on methyl acrylate, methylmethacrylate and
methacrylic acid. It is insoluble in acidic media, but dissolves by salt
formation above pH 7.0. Apart from its enteric properties, its
dissolution at a higher pH value allows targeted colon drug delivery. Its molecular weight, acid value and glass transition temperature are approximately 2,80,000 g/mol, 70 mg KOH/g polymer
and 48 C respectively. Due to low minimum film forming temperature only small amounts of plasticizer are required to get a
smooth film formation. It is available in the form of aqueous
dispersion (30%).
A current review on recent research publications based on
Eudragit S 100 is described as follows. It is used in formulation of
transdermal patch, nanoparticles, microparticles, microballons,
solid dispersions and spherical crystals. It has been used for various
applications such as colon specific drug delivery, sustain release,
bioavailability enhancement, improvement in micromeritic properties etc as shown in Table 5. Madan et al. [40] evaluated the
sustain release potential of Eudragit S100 by formulating transdermal patches of donepezil using various polymers along with
plasticizer and penetration enhancer. Eudragit S100, Eudragit E100
and HPMC were used as matrix forming agents in the formulation
of patches. They concluded that transdermal patch can extend the
release of donepezil for many hours with enhanced bioavailability.
Hence Eudragit S 100 can be used to extend release of domepezil in
transdermal patches. Li et al. [16] evaluated colon specific drug
delivery potential of Eudragit S 100 based enteric coating of model
drug. Enteric coating was achieved by applying Eudragit S 100 to
microencapsulated 5-Flurouracil and leucovorin coloaded with
folate-chitosan nanoparticles. When the pH value reached the
soluble threshold of Eudragit S-100, a constant and slow drug
release was observed. Eudragit S100 can be used for selectively
targeting drugs to colon in the chemotherapy of colon cancer.
Nandy et al. [41] formulated and characterized delayed release
multi particulates system of indomethacin. Microspheres were
formulated by using a novel quasi emulsion solvent diffusion
technique using combination of ethyl cellulose (EC) and Eudragit RS
100/Eudragit S100 . Drug release decreased significantly (p < 0.05)
with increase in amount of Eudragit polymer. Therefore this
approach suggested that the combination of EC and Eudragit S100
microspheres may be useful for the delivery of maximum amount
of indomethacin to the colon.
No literature was found for Eudragit S 12,5 in pubmed indexed
38
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
Table 5
Reported literature on Eudragit S 100, 12,5 and FS 30 D.
Drug name
Eudragit S 100
Donepezil
5-fluourouacil (5FU) and
leucovorin
Raloxifene
hydrochloride
Indomethacin
Dosage form/delivery
system
Method of Preparation
Transdermal Patches
Solvent casting technique
Nanoparticles
microencapsulated with
enteric polymers
Nanocapsules
Interfacial deposition of preformed polymer
Tartrazine (model
substance)
Thymidine
*
References
Extended release, enhanced bioavailability, avoids the first [40]
pass effect
Ionic gelation followed by solvent evaporation Selectively targeting drugs to colon in the chemotherapy of [16]
method
colon cancer.
Emulsion solvent diffusion method
Best activity was observed for RH-loaded Eudragit S100
nanocapsules after 72 h
Combination of EC and Eudragit S100 delivered maximum
amount of drug to colon.
Solid dispersion of drug-Eudragit S 100 to overcome the
problems of dose dumping after the rupture of the pH
dependent alginate gels.
Sustain release and increased residence time
Enteric coated
nanoparticles
Dextran Microspheres by emulsificationcrosslinking method and enteric coating by oilin-oil solvent evaporation method.
Double emulsion method followed by freeze
drying
[47]
Eudragit S100 retard the release of drug in gastric and
intestinal pH and the drug released in colon due to the
degradation of dextran by colonic enzymes.
Nanoparticles almost completely released at pH 7.4 after 8 h [48]
reduced blood pressure for more than 30 h
Microspheres
Spherical crystals
Oil/oil emulsification method
Solvent change method
Colon specific drug delivery
Spherical crystals with improved micromeritic properties.
[49]
[50]
*
*
*
*
Multiparticulate (enteric
coated with FS 30 D)
compressed in to tablets
Multiple-unit tablet
compressed from entericcoated pellets
Enteric-coated HPMC
capsules
Direct compression
Delayed release property was preserved.
[51]
Multi-particulates system
in the form of microspheres
Dextromethorphan Solid dispersion (modified
in situ gelling alginate
formulations).
Nizatidine
Encapsulated
microballoons
5-Flurouracil
Enteric coated dextran
microspheres
Peptide Val-LeuPro-Val-Pro-Arg
(VLPVPR)
Flurbiprofen
Mebendazole
Eudragit S 12,5
*
Eudragit FS 30 D
Theophyline
Application
Novel quasi emulsion solvent diffusion
technique
Solvent evaporation method
[44]
[41]
[45]
[46]
Film coating technique
An optimal coating was obtained by mixing two acrylic
[42]
polymers: relatively brittle Eudragit® L30 D-55 with more
®
flexible Eudragit FS 30 D.
Optimized coating process(fluid bed apparatus) Ready-to-use enteric-coated HPMC capsules for the use in [43]
retail or hospital pharmacy or R&D sections of
pharmaceutical industry.
No literature found.
journals. But few articles were published on the use of Eudragit FS
30 D in various dosage forms such as multiparticles, tablets and
capsules for enteric coating as shown in Table 5. Dreu et al. [42]
produced multiple-unit tablet compressed from enteric-coated
pellets. An optimal coating was obtained by mixing two acrylic
polymers: relatively brittle Eudragit® L30 D-55 with more flexible
Eudragit® FS 30 D. The final formulation released 9% drug in acidic
medium. In addition to coating, biconvex shape of tablet and protective coating of Kollidon VA 64 also played a significant role in
achieving enteric coating. Huyghebaert et al. [43] developed an
alternative method for enteric coating of HPMC capsules that
avoids the sealing step before coating, resulting in ready-to-use
enteric-coated capsules for the use in retail or hospital pharmacy
or R&D sections of pharmaceutical industry and for the production
of enteric-coated heat and moisture sensitive biomaterials. The
release of thymidine in 0.1 N HCl after 2 h from capsules coated
with Eudragit L30D-55, Eudragit FS 30 D, Aqoat AS-HF and Sureteric
was 0.6 ± 0.03, 0.6 ± 0.3, 1.2 ± 0.2 and 7.3 ± 1.9% respectively. The
alternative method was reproducible and offered a way to overcome the time-consuming and expensive sealing step required
using the conventional coating procedure.
2.5. Eudragit NE 30D, NE 40D and NM 30D
Eudragit NE 30D, NE 40D and NM 30 D are the aqueous
dispersion of a neutral copolymer based on ethyl acrylate and
methyl methacrylate. These are milky white liquid of low viscosity
with a faint characteristic odour. All the three grades have minimum film forming temperature of 5 C. Both NE 30D and 40 D are
having a molecular weight of approximately 7,50,000 g/mol
whereas NM30 D have molecular weight of 6,00,000 g/mol. Glass
transition temperature (Tg) of NE 30 D and 40D are ~8 C whereas
NM 30 D is having glass transition temperature of ~11 C. Eudragit
NE 30D, NE 40 D and NM 30 D are available in the form of aqueous
dispersion 30, 40 and 30% respectively. All are highly flexible in
nature and does not require incorporation of plasticizer. They are
used in formulation of controlled release products which are independent of pH of gastrointestinal tract.
An extensive review on Eudragit NE 30D revealed that it is used
for modified release formulations in various dosage forms such as
multiparticles, microparticles, pellets, films etc as shown in Table 6.
Amrutkar et al. [52] designed multiparticulate floating drug delivery system of zolpidem tartarate to prolong the gastric residence
time and to improve bioavailability. The system consists of effervescent layer (sodium bicarbonate) and polymeric layer (Eudragit
NE 30D) membrane. In-vitro drug release of the system were
dependent on Coating level of the polymeric membrane (Eudragit(®) NE 30D) played a significant role in drug release. Kumaria
et al. [53] developed and evaluated Loratidine buccal films for
allergic rhinitis. Polymeric buccoadhesive films of loratidine were
prepared using hydroxypropylmethyl cellulose (HPMC)-E5 and
K100 blend and Eudragit® NE 30D as retardant. Films were prepared using solvent-casting method. Increase in Eudragit® NE 30 D
content in the film decreased the hydration, erosion and drug
release, but enhanced the mucoadhesion time.
Current literature review on Eudragit NE 40 D suggests that it is
used for various pharmaceutical applications like modified release,
enhancement of bioavailability etc as bucoadhesive films and non
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
39
Table 6
Reported literature on Eudragit NE 30 D.
Drug name
Dosage form/delivery system
Method of Preparation
Application
References
Coated with effervescent layer and
polymeric membrane
Solvent-casting method
Theophylline or cimetidine
Multiparticulate DDS
Venlafaxine hydrochloride
Pellets
Extrusion-spheronization followed by
coating.
Extrusion/spheronization followed by
coating
Rapid floating and modified drug
release was obtained.
Mucoadhesion and release retardation
was achieved with HPMC and eudragit
NE 30 D respectively.
Modified release
[52]
Loratidine
Multiparticulate floating drug delivery
system (pellets)
Prolonged release Buccoadhesive film
Tamsulosin hydrochloride
Sustain Release microparticles
Single-step matrix coating
Urapidil
Drug layer pellets followed by coating
Centrifugal granulation and fluid bed
coating
Buccoadhesive films
Nonocclusive dermal therapeutic
system
*
Eudragit NE 30 D
Zolpidem tartarate
Eudragit NE 40 D
Prednisolone
Miconazole nitrate
Eudragit NM 30 D
*
*
[53]
[56]
Differences in the film micro-structure
and surface roughness influence the
in vivo release
Optimum ratio of Aquacoat® and
Eudragit® NE30D in the matrix (9:1)
provides a sustained-release
Improvement in bioavailability
[57]
solvent-casting method
Matrix system
Enhanced bioavailability
In vitro control of drug release for at
least 24 h
[54]
[55]
*
*
*
[58]
[59]
No literature found.
occlusive dermal therapeutic systems as shown in Table 6. Kumria
et al. [54] prepared buccoadhesive films of prednisolone by solventcasting method using hydroxyl propyl methyl cellulose (K100),
Carbopol 940 and/or Eudragit® NE 40 D. Buccal route was found as a
viable option for delivery of prednisolone. Minghetti et al. [55]
prepared self-adhesive matrix made of a mixture of Plastoid E
35 L, an adhesive hydrophilic polymer, and eudragit NE 40 D, a
nonadhesive hydrophobic polymer able to modify the drug release.
All systems sustained drug release for at least 24 h. No literature
was found for Eudragit NM 30D based formulations in pubmed
indexed journals.
2.6. Eudragit RL 30 D, RLPO, RL100 and RL 12,5
Eudragit RL 30 D, RLPO, RL100 and RL 12,5 are copolymers of
ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups. The ammonium groups are present as salts and make the polymers
permeable. RL 30D is a milky white liquid of low viscosity with a
faint characteristic odour. Molecular weight of RL 30D is approximately 32,000 g/mol. Its minimum film forming temperature and
glass transition temperature are 40 C and 55 C respectively. Alkali
value of RL 30D is 32.3 mg KOH per g of polymer. RL 30D is available
in the form of 30% aqueous dispersion. RL 30D exhibit pH dependent swelling. RL 30D is primarily used in the formulation of sustained release products. Eudragit RLPO is a solid substance available
in the form of white powder with a faint amine like odour whereas
eudragit RL100 is a solid substance available in the form of colourless, clear to cloudy granules with a faint amine like odour.
Molecular weight, alkali value and glass transition temperature of
both RLPO and RL 100 are same i.e. 32,000 g/mol, 28.1 mg KOH/g
polymer and 70 C respectively. RLPO and RL100 is mainly used for
customized release profile by combination of RL and RS grades in
different ratios and they are also suitable for matrix structures.
Eudragit RL 12,5 is light yellow liquid of low viscosity, clear to
slightly cloudy with a characteristic odour of solvents. RL 12,5 is
available in the form of a 12.5% organic solution. Its molecular
weight, alkali value and applications are same as RLPO.
An extensive literature review on Eudragit RL 30D revealed that
this polymer is primarily used for controlled release DDS as shown
in Table 7. Kibria et al. [60] investigated the effect of physico-
-vis eudragit RL30D and
chemical properties of the polymers vis-a
RS30D on the release profile of ketoprofen from pellets. Extruded
and spheronized pellets were coated with 15% (w/w) polymers
Eudragit RL 30 D and Eudragit RS 30 D. It was revealed that Eudragit
RL 30 D has the effect to increase the initial drug release more
significantly than RS 30D. Lingam et al. [61] formulated matrix type
multiple-unit (minitablets) floating drug delivery system for
captopril. The system consists of core units which are coated with
-vis inner seal coat, effervescent layer
three successive layers vis-a
and an outer gas-entrapped polymeric membrane of an polymethacrylates. Eudragit RL30D and its combination formulations
exhibited floating.
Review on Eudragit RLPO is primarily used for sustaining drug
release in diverse drug delivery systems like nanoparticles,
mucoadhesive tablets and patches, solid dispersions etc as shown
in Table 7. Singh et al. [62] investigated the effect of iron oxide in
the development of mucoadhesive tablets of cinnarizine using
Eudragit RLPO. Eudragit RLPO and iron oxide exhibited potential
for gastroretentive and mucoadhesive drug delivery systems.
Pandey et al. [63] attempted site specific drug delivery by
formulating bilayered gastroretentable mucoadhesive patch
(stomach). Both Eudragit RSPO and RLPO were used for formulation of patch. Patches could control the drug release up to 12 h,
with mucoadhesion. Sahoo et al. [64] formulated solid dispersion
of verapamil using Eudragit RLPO or Kollidon SR to sustain drug
release. Extended the drug release upto 12 h was attained in case
of Eudragit RLPO.
A widespread literature review on Eudragit RL 100 revealed that
it is used for controlled release and bioavailability improvement
approaches in various dosage forms such as nanoparticles, tablets,
buccal films, transdermal patches, ophthalmic inserts etc as shown
in Table 7. Singh et al. [65] prepared atazanavir nanoparticles
loaded with Eudragit RL 100 to improve oral bioavailability. These
nanoparticles were prepared by nanoprecipitation method.
Eudragit L100 based nanoparticles showed improved bioavailability potential. Ofokansi et al. [66] prepared ibuprofen tablets
from interpolyelectrolyte complexes (IPECs), formed between
Eudragit RL100 and chitosan, by nonstoichiometric method, and
tablets based on the above complex by wet granulation method.
The complex was capable of preventing drug release in the stomach
and small intestine and helped colon specific drug delivery. Palem
40
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
Table 7
Reported literature on Eudragit RL 30 D, RLPO, RL100 and RL 12,5.
Drug name
Dosage form/delivery system
Method of Preparation
Application
References
Eudragit RL 30D
Diltiazem HCl
Matrix Tablets
Controlled release
[69]
Ambroxol hydrochloride
Pellets
Pellet
Captopril
Minitablets
Stability was dependent on storage
condition and physicochemical
property of the polymer.
Proper selection of polymeric materials
based on their physico-chemical
properties sustained the drug release.
Only the system using Eudragit RL30D
and combination of them as a gasentrapped polymeric membrane could
float.
[70]
Ketoprofen
Dry mixing and direct compression
followed by coating with Eudragit NE
30D
Extrusion-spheronization technology
followed by coating with Eudragit NE
30D
Extrusion spheronisation technique
followed by coating with Eudragit Ne
30D and RS 30D
Direct compression followed by coating
Eudragit RLPO
Acyclovir
Nanoparticles
Nanoprecipitation technique
[71]
Cinnarizine
Mucoadhesive tablets
Simplex lattice design
Lercanidipine HCl
Gastroretentable mucoadhesive patch
Layering technique
Domperidone
Bilayered mucoadhesive buccal patches
Solvent casting technique
Metoprolol
Verapamil hydrochloride
Solid dispersion
Solid dispersion compressed into a
tablet
Solid dispersions compressed into
tablet
Melting and solvent method
Direct compression
As acyclovir: Eudragit RLPO ratio
increased from 1:1.5 to 1:2, particle size
and drug entrapment increased It also
produced sustain release.
Eudragit RLPO and iron oxide
combination showed high level
potential for fabricating gastroretentive
as well as mucoadhesive drug delivery
systems.
Patches prepared using the
combination of Eudragit RSPO and RLPO
could control the drug release up to
12 h
Bilayered mucoadhesive buccal patches
with desired permeability could be
prepared
RLPO showed higher release than RSPO.
The tablet containing Eudragit RLPO has
extended the release rate for 12 h
Eudragit RLPO coevaporates (1: 5)
displayed extended release of drug for
12 h
Eudragit RL100
Griseofulvin
Polymer-coated drug
Nanoparticles
Ibuprofen
Metformin hydrochloride
Domperidone
Azithromycin
Tablet with interpolyelectrolyte
complexes (IPECs), formed between
Eudragit RL100 (EL) and chitosan (CS).
Matrix tablet
Buccal films
Opthalmic inserts
Coated drug particles can be potentially
used for controlled release.
To improve bioavailability & in
prolonged drug release
Exploited successfully for colontargeted delivery of ibuprofen
[75]
Atazanavir
Porous hollow fiber membrane-based
antisolvent crystallization
Nanoprecipitation method
Wet granulation technique
Hot-melt extrusion
Modified solvent casting method
[76]
[67]
[68]
Lercanidipine hydrochloride
Sulfacetamide
Transdermal patches
Nanosuspension
Solvent evaporation technique
Solvent displacement method
Azelastine hydrochloride
Microspheres
Solvent evaporation technique
Zidovudine
Cloricromene
Transdermal delivery
Nanoparticle suspensions
Solvent evaporation method
Quasi-emulsion solvent diffusion
technique
used to sustain drug release
improved bioavailability
Prolonged release time and improved
ocular availability.
Drug release sustained upto 24 h.
Formulation of sulfacetamide in
Eudragit RL100 improve the availability
of sulfacetamide at the intraocular level.
Prolonged release of the drug over the
period of 6 h.
Increased permeation
Improves the shelf life and
bioavailability of this drug after
ophthalmic application
Eudragit RL 12,5
*
*
*
*
*
Promethazine hydrochloride
*
Coevaporation and coprecipitation
techniques
Wet granulation
[60]
[61]
[62]
[63]
[72]
[73]
[64]
[74]
[65]
[66]
[77]
[78]
[79]
[80]
[81]
No literature found.
et al. [67] prepared domperidone (DOM) hot-melt extruded (HME)
buccal films by using combination of HPMC E5 LV or Eudragit RL100
as polymeric carriers along with some other carriers exhibited 1.5
times improved bioavailability. Thakur et al. [68] formulated the
bioerodable insert of azithromycin to prolong the release time and
improve the ocular availability. Azithromycin insert was prepared
using hydroxyl propyl methyl cellulose (HPMC) and Eudragit
RL100. The formulation (comprising of 1.5% HPMC and 3% Eudragit
RL100) showed release of drug over a 12 h in a steady and
controlled manner. No research articles found for Eudragit RL 12,5
in pubmed indexed journals.
2.7. Eudragit RS 30D, RSPO, RS 100 and RS 12,5
Eudragit RS 30D, RSPO, RS100 and RS 12,5 is a copolymer of
ethyl acrylate, methyl methacrylate and a low content of
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
methacrylic acid ester with quaternary ammonium groups. The
ammonium groups are present as salts. Presence of salts makes
them more permeable. Eudragit RS 30 D is a liquid of low viscosity
with milky white color showing faint characteristic odour. Eudragit
RSPO is white powder with a faint amine like odour. Eudragits RS
100 is colorless granule with a faint amine like odour. Eudragit RS
12,5 is a light yellow liquid of low viscosity, clear to slightly cloudy
with a characteristic odour of the solvents. Molecular weight of
each of the above grades is 32,000 g/mol. Eudragit RS 30D, RSPO,
RS100 and RS 12,5 are available in the form of 30% aqueous
dispersion, powder, granules and 12.5% organic solution respectively. All the above four grades of Eudragit are insoluble. They
exhibit low permeability with pH independent swelling. These
polymers are used for controlled and customized release profile by
combination of RL and RS grades in different ratios.
Eudragit RS 30 D is extensively used for formulation of sustain
release products. The current literature survey suggests that this
polymer has been used in formulation of pellets, coating of pellets
osmotically driven pellets etc as shown in Table 8. Piao et al. [82]
developed sustained release osmotic pellet coated of oxymatrine.
Extrusion/spheronization followed by coating with Eudragit RS 30
D was adopted. They found that the F3 formulation, prepared with
20% NaCl and an 8% coating level (Eudragit RS 30 D), showed a
continuous NaCl-induced water influx into the pellets providing a
41
gradual sustained release of OMT for over 12 h. Kibria et al. [60]
investigated the release of ketoprofen from pellets to study the
effect of physico-chemical properties of polymers. The drug containing core pellets were prepared by extrusion spheronisation
technique and subsequently coated with 15% (w/w) polymer load of
the combination of Eudragit RL 30 D & Eudragit RS 30 D. It was
revealed that Eudragit RL 30 D has the effect to increase the initial
drug release more significantly where as Eudragit RS 30 D has the
effect to minimize the initial drug release but increase the terminal
drug release more significantly.
An extensive review on research publication on Eudragit RSPO
revealed that it is mainly used in the sustaining drug release as
shown in Table 8. Eudragit RSPO has been used in the formulation of
microballons, tablets, microspheres and microtablets. Porwal et al.
[83] prepared microballons of propranolol HCl by the non-aqueous
oil in oil emulsion solvent diffusion evaporation method using
Eudragit RSPO as polymer. The drug release from microballoons
showed a biphasic pattern with an initial burst release, followed by
sustained release for 12 h Abbaspour et al. [84] prepared and
characterized ibuprofen pellets based on Eudragit RSPO and RLPO or
their combination. Eudragit RLPO compare with Eudragit RSPO
resulted in pellets with high crushing strength; however, Eudragit
type did not have a significant effect on elastic modulus.
Literature review on applications of eudragit RS100 suggests
Table 8
Reported literature on Eudragit RS 30D, RSPO, RS 100 and RS 12,5.
Drug name
Dosage form/delivery system
Method of Preparation
Application
References
Eudragit RS 30D
Oxymatrine
Osmotically driven Pellets
Gradual sustained release for 12 h
[82]
Ambroxol hydrochloride
Pellets
Stable and sustain release formulation
[70]
Diclofenac sodium
Pellets
Extrusion/Spheronization followed by
fluid bed coating
Extrusion-spheronization technology
followed by coating
Powder layering technology and air
suspension technique
[87]
Ketoprofen
Pellets
Extrusion and spheronisation followed
by coating
Diclofenac sodium
Pellets
Roto-agglomeration
Retarded the drug release rate and
varied according to the type and
amount of plasticizers
Eudragit RS 30 D has the effect to
minimize the initial drug release but
increase the terminal drug release more
significantly.
Eudragit RS 30 D provided membranes
successfully controlling drug release
over an extended period of 24 h
Eudragit RSPO
Propranolol hydrochloride
Microballoons
Non-aqueous O/O emulsion solvent
diffusion evaporation method
[83]
Alfuzosin hydrochloride
Tablets
Direct compression
Stavudine
Ibuprofen
Microspheres
Pellets
Solvent evaporation method
Extrusion-spheronization
Lobenzarit disodium
Theophylline
Eudragit RS 100
Genistein
Metformin HCl and Acarbose
Tablets
Microtablets
Direct compression
Rotary tablet press
Drug release showed a biphasic pattern
with an initial burst release, followed by
sustained release for 12 h
The release of Alfuzosin was prolonged
for 20 h
Sustain release
Eudragit RLPO and RSPO did not have a
significant effect on elastic modulus.
slower release rate
Sustained-release
Nanostructured lipid carrier (NLC)
Bbilayer tablet
Matrix tablet followed by coating
Terbinafine hydrochloride
positively charged controlled-release
polymeric Nanoparticles as eye drop
Nanopreciptation method
Lornoxicam
matrix-type transdermal patch
Solvent evaporation technique
Clotrimazole
Bioadhesive Vaginal tablets containing
microspheres
Spray drying technique
3.3-fold increase in corneal penetration
Extended release of metformin HCl for
12 h from one layer
Coating with eudragit RS100 polymer
minimized initial burst release
Increased drug mean residence time
and improved its ocular bioavailability
four fold.
Sustain release and enhanced
bioavailability
Controlled intravaginal drug release
[85]
[93]
Verapamil hydrochloride
Melt-emulsification technique
Solvent evaporation and cogrinding
techniques
Wet granulation method
*
*
*
*
Eudragit RS 12,5
*
*
No literature found.
[60]
[88]
[89]
[90]
[84]
[91]
[92]
[94]
[95]
[86]
[96]
42
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
that it has been used extensively in the formulation of following
-vis nanoparticle, bilayer tablet, matrix
types of dosage form vis-a
tablet, transdermal patch, vaginal tablets etc as shown in Table 8.
Zhang et al. [85] formulated nanostructured lipid carrier (NLC)
surface modified with Eudragit RS100 Model drug genistein was
selected. NLC was produced using the melt-emulsification technique followed by surface absorption of Eudragit RS 100. The
Eudragit RS 100 increased the surface zeta potential from 7.46 mV
to þ13.60 mV, by uniformly forming a spherical coating outside the
NLC surface, as shown by transmission electron microscopy images.
Particle size growth was inhibited by Eudragit RS 100. Increased
corneal penetration producing a 3.3-fold increase in apparent
permeability coefficients was attributed to Eudragit RS100. Baviskar et al. [86] prepared matrix-type transdermal drug delivery
system of lornoxicam with the addition of hydrophilic and hydrophobic polymers in different ratios. Transdermal patches of lornoxicam were designed with ethyl cellulose:polyvinylpyrrolidone
and Eudragit RL 100:Eudragit RS 100 in different ratios with propylene glycol as plasticizer (5%) and tween 80 as permeation
enhancer using the solvent evaporation technique. It was observed
that both the patches significantly controlled inflammation and
showed analgesic effect from the first hour (P < 0.05). Formulations
Table 9
Patents on applications of Eudragit.
S. No
Title of the patent
Invention
Patent Number
Inventors
Date
References
1
Colonic delivery using zn/
pectin beads with a eudragit
coating.
US 20080124279
A. Andremont H. Huguet
05/29/2008
[97]
2
Ursodeoxycholic acid-synthetic
hydrotalcite-eudragit hybrid,
pharmaceutical composition
containing the same and
method for preparing the same
US 20120156263
J.H. Choy, G.E. Choi, M. C. Park, H. C.
Chang
06/21/2012
[98]
3
Modified release tablet
formulations with enhanced
mechanical properties
US 20070104782
S. H. Amir
C.E. Melissa
02/08/2007
[99]
4
Curcuminoid complexes with
enhanced stability, solubility
and/or bioavailability
US20140271530
H. Tummala, S. Kumar
09/18/2014
[100]
5
Improved stabilization of
misoprostol
EP0896823
C. David Tsay,
R. Jen
Lin Hue In
Lu Shu-bin
09/25/2002
[101]
6
Sustained release
pharmaceutical composition
EP0322277
H. Stevens,
M. Chariot,
F. Arnold,
G. Lewis
01/22/1992
[105]
7
Colonic delivery of metallodependent enzymes
US 20080199528
A. Andremont,
H. Huguet
08/21/2008
[106]
8
Coated senna extract granules
WO/2011/014976
P. H. Jorge
10.02.2011
[102]
9
ketoprofen microgranules,
method for preparing same and
pharmaceutical compositions
Formulation stabilizer for
proton pump inhibitors
The systems include pectin
beads cross linked with zinc or
any divalent cation of interest,
which beads are then coated
with Eudragit®-type polymers.
The ursodeoxycholic acidsynthetic hydrotalcite-Eudragit
hybrid was used for bittertaste-blocking effect and
improved body absorption rate
with high solubility.
Eudragit L100-55 for said
pharmaceutical formulation
which achieves a desired
hardness for tablets made from
the formulation.
Curcuminoid-eudragit
complex, which enhance the
bioavailability of the curcumin
component.
Misoprostol was complexed
with various grades of Eudragit
RS series, Eudragit RL series,
Eudragit S, Eudragit L., The solid
dispersions were stable 6and
showed sustain release.
Controlled dissolution of the
active principle independently
of the pH, which consists of
micro particles containing the
active principle, coated with a
mixture of ethylcellulose and
Eudragit RS.
Pectin beads are crosslinked
with zinc ions and the pectin
beads are coated with a
Eudragit® polymer.
Senna extract with 20%
sennosides are granulated with
Eudragit L 100 and then coated
with Eudragit L 30 D 55
ketoprofen micro granules of
eudragit RL and RS exhibited
prolonged release
The polymeric base is
cholestyramine-OH, Eudragit
EPO, chitosan, or a mixture
thereof. The composition
stabilizes the benzimidazole
derivative proton pump
inhibitor in a humid
environment
One active substance and at
least one coat comprising
Eudragit E The formulation may
be used for releasing up to
about 55% of a total dose as a
loading dose in order to manage
pain.
WO/2000/064432
L. C. Marechal,
D.S. Pascal
11/02/2000
[103]
US 20060013880
F. Robert, R. Narayan, Z. Joseph
H. Ping
01/19/2006
[104]
US 20150250733
O. Isa
09/10/2015
[107]
10
11
Oral drug delivery formulations
Ch.N. Patra et al. / Future Journal of Pharmaceutical Sciences 3 (2017) 33e45
A3 and B3 were found to enhance the bioavailability of lornoxicam
by 3.1 and 2.7 times, respectively, compared to the oral dosage
form. Hence, lornoxicam can be formulated into transdermal
patches for sustain release characteristics. As far as Eudragit RS 12,5
is considered no such research article is published in any indexed
research journals.
3. Recent patents on eudragit based formulations
Recent reviews on various patents published on Eudragit based
formulation were collected. It was observed that Eudragit based
formulation has been patented for diversified applications. They are
used for colonic drug delivery, bitter taste masking, improved
hardness, enhanced stability, improved bioavailability, prolonged
drug release etc as shown in Table 9. Antoine et al. [97] prepared
pectin beads cross linked with zinc or any divalent cation for
colonic delivery of drugs. The beads were then coated with
Eudragit- FS 30D, LE 30D and NE 30D. The use of zinc cations to
crosslink the pectin is particularly preferred to provide a stable
metallo-enzyme formulation for the lower intestinal or colonic
delivery of such an enzyme. Choy et al. [98] patented hybrid of
ursodeoxycholic acid-synthetic hydrotalcite-and Eudragit for
bitter-taste-masking and improved body absorption rate with high
solubility. Ursodeoxycholic acid is bitter in taste. The inventors
found that a hybrid obtained by incorporating ursodeoxycholic acid
between the layers of hydrotalcite, which is used as an antacid and
a stomachic, and then coating with Eudragit, which is an enteric
coating, blocks the bitter taste of ursodeoxycholic acid and simultaneously shows improvement of dissolution rate and high
bioavailability. Shojaei et al. [99] patented on how the Eudragit
L100-55 played a significant role in achieving desired hardness for
tablets. The present invention relates to a pharmaceutical composition comprising a pharmaceutically active agent and a Eudragit L
100-55 which is useful to achieve the required release and desired
compressibility. Tummala et al. [100] patented enhancement of
bioavailability of the curcumin by complexing curcuminoid with
Eudragit®. Chen et al. [101] prepared stable and sustain release
solid dispersions of misoprostol with various grades of Eudragit RS
series, Eudragit RL series, Eudragit S and Eudragit L. Periano [102]
patented stable formulation of sennoside by granulation of senna
extract (20% sennosides) with Eudragit L100 and then coated with
Eudragit L 30 D 55. This product was stable for a long time and has
good organoleptic properties (taste and odour). Christophe et al.
[103] patented microgranules of ketoprofen using eudragit RL and
RS for prolonged release. Aqueous dispersions of Eudragit RL and RS
were used for the preparation of microgranules. Robert et al. [104]
attempted to stabilize benzimidazole derivative proton pump inhibitors. The present invention provides a composition containing a
benzimidazole derivative proton pump inhibitor and a polymeric
base selected from the group consisting of cholestyramine-OH,
Eudragit E-PO, chitosan, or a mixture thereof. The composition of
the present innovation provides improved stability for the benzimidazole derivative proton pump inhibitor under naturally
occurring humidity ranges so that degradation during storage and
in the stomach is minimized. It can be easily manufactured by
directly admixing the benzimidazole derivative proton pump inhibitor with the polymeric base.
4. Conclusion
This represents a comprehensive review of 107 references
where various grades of Eudragit were used to develop formulations with widespread applications. The various drugs and techniques used in Eudragit based formulations have been described in
sufficient detail to give the reader a basic understanding about the
43
role of Eudragit in different formulations. Hence this review
manuscript can be used as ready reckoner for researchers to
develop Eudragit based drug delivery systems.
Acknowledgements
The authors are thankful to management and principal, Roland
Institute of Pharmaceutical sciences, Berhampur, India for support
and encouragement.
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