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Review of Literature on Drug & Excipients

 Samia A. Nour et al., 2016, studied formulation & evaluation of colon targeted chewable
tablet of Bumadizone calcium using (PVP K 30), maize starch, mannitol and eudragit S-100, L-
100 polymer to transport drug to colon for local treatment of ulcerative colitis. The result of
two independent variables, Eudragit S100 & Eudragit L 100 and differ release was study at
12hrs. From in-vitro & in-vivo study formulation composed of (EU S100 1:3, 250 mg
mannitol, 50mg maize starch and 20mg cinnamon powder) minimizes drug release in the upper
gastrointestinal tract and at colon it gives highest release.
 Maimana A. Magdy et al., 2013, studied stability indicating spectrophotometric methods
for determination of bumadizone in the presence of its alkaline degradation product The four
methods were found to be specific for determination BUM in presence of different
concentrations of DEG I and had successfully applied for the determination of BUM in
Octomotol tablets.
 Samia A. Nour et al., 2014, studied Bumadizone calcium dihydrate microsphere were
dense into tablet contain the (NSAIDS) non-steroidal anti-inflammatory. The effect of polymer
Eudragit RS 100, ethyl cellulose, cellulose acetate butyrate. Candidate formula F15
(microspheres prepared using a ratio of 18:1 for BDZ:CAB and compressed into tablets using
50% pectin and 50% Avicel in the coat) was able to modulate drug release in colon by avoiding
drug release in the gastric ambient, and reaching the colonic targeting where 99.7% release was
achieved within 12 hrs.
 Sateesh Kumar Vemula et al., 2015, studied to formulate and study the pharmacokinetics
of colon-specific pulsatile ketorolac tromethamine tablets using double-compression coating
method In this, inner compression coat made of sodium starch glycolate as swelling layer and
outer compression coat (release controlling layer) contains sodium alginate and Hydroxypropyl
methylcellulose K 15M. From the in vitro drug release studies, F5 tablets sodium starch
glycolate: HPMC K15M in ratio 1:1 showed 5.02 ± 0.16% drug release in 5 h and it was
progressively expanded to 99.78 ± 0.64% in 24 h that demonstrate the colon-specific drug
release.
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 Rohit Mehta et al., 2013, studied to prepare matrix tablets of naproxen using a
hydrophobic polymer, i.e., Eudragit RLPO, RSPO, and combination of both, by wet
granulation method. The tablets were further coated with different concentrations of Eudragit
S-100, a pH-sensitive polymer, by dip immerse method. In vitro drug release studies of tablets
were carried out in different dissolution media, i.e., 0.1 N HCl (pH 1.2), phosphate buffers pH
6.8 and 7.4, with or without rat cecal content matrix tablet of naproxen was formulate with
Eudragit S 100 like a pH sensitive polymer. The outcome demonstrate that the tablets coated
with Eudragit S-100 show a sustain release of 94%.
 Minjie Sun et al., 2014, studied to develop colon adhesive pellets of 5-aminosalicylic acid
(5-ASA) for the treatment of ulcerative colitis. The core of the pellet was formulated from
bioadhesive agents, Carbomer 940 and Hydroxypropyl cellulose (HPC), by
extrusion/Spheronization method and coated with Surelease1 as inner layer for waterproof and
with Eudragit1 S100 as outer layer for pH control Microcrystalline cellulose 101 (PH 301)
was found to be the best agent for pellet core. The ratio of CP940 to HPC should be kept as
(1:1) to achieve high bioadhesion. When the amount of Surelease1 was from 16% to 20% and
of Eudragit S100 was 28%, the dissolution profiles of coated pellets revealed no drug release in
the artificial gastric fluid (pH 1.0) within 2 hrs and less than 10% was released in phosphate
buffer (pH 6.0) within 2 hrs whereas complete dissolution was observed in colonic fluid of pH
7.4 for 20 hrs.
 Zan Liu et al., 2016, studied sticking of pellets caused by EudragitL30D-55 was observed
during the release process, leading to change in drug release. Talcum powder (talc) was used in
esomeprazole magnesium pellets to prevent sticking and modify release of pellets. Talc as
antiadherent could successfully prevent the pellets from aggregating in vitro by the two
methods tested: (i) physically mixed with resulted pellets and (ii) coating the resulted pellets.
Besides, talc levels in sub coat had different influences on drug release from coated pellets in
phosphate buffer solution (pH 6.8 and 6.0) and distilled water, attributing to the different
release mechanisms of pellets in these three media. Talc could not only prevent the sticking
during release process, but also affect the release of the EMZ from the enteric-coated pellets.

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 Pranjal Kumar S et al., 2012, studied to develop colon targeted film coated tablets of
ibuprofen using HPMC K4M, Eudragit L100 &Ethyl cellulose as carriers. The formulation of
drug released 98.34%. & to provide targeting of ibuprofen for local action in the colon due its
least release of the drug in the first 5 hr. The effect of film coated tablet system is a capable
vehicle for prevent quick hydrolysis in gastric environment and recovering oral Bioavaibility of
ibuprofen for the treatment of disease of colon region.
 Mihir K Raval, Riddhi V Ramani et al., 2013, studied to develop intestinal-targeted
pellets of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative colitis and
Crohn’s disease by extrusion and Spheronization method. In this study, the pellets were coated
by spray coating technique using Eudragit S100 as an enteric polymer. Optimization of binders
like PVP K30, pectin, guar gum, sodium alginate, and xanthan gum in 2% w/v. On the basis of
physical appearance roundness, smoothness, and strength of the pellets, PVP K30 was selected
as a binder for further pellet preparation.
 Cheng et al.25 developed Time- and pH-dependent colon-specific drug delivery systems
(CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA).
DS tablets and 5-ASA pellets were coated by Ethylcellulose (EC) and methacrylic acid
copolymers (Eudragit® L100 and S100), respectively. Release profile of time-dependent DS
coated tablets was not influenced by pH of the dissolution medium on the contrary release
profile of pH dependent 5-ASA coated pellets was significantly governed by pH. It was
concluded that, on using regular coating techniques also colon specific drug delivery can be
obtained.
2.2Review of Literature on Drug Delivery System

 Uma Devi S, Suresh Set.al.,2010, The aceclofenac using chitosan as a Microbially

degradable polymeric transporter and to coat the optimized batches with a pH dependent
polymeric coating solution containing Eudragit L100 & S100.The entire of aceclofenac
released from the chitosan tablets at changed time interval was estimated by UV
spectrophotometric method. The results of chitosan tablets are capable for colon targeting of
match the Chrono biological symptom for effective treatment of rheumatoid arthritis.
 Reza Mahjub et al., 2016, Studied development of enteric coated pellets containing
Lansoprazole by an extrusion/ Spheronization technique. Eight different formulations based on

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lactose and six different formulations based on mannitol, consisting of different portions of
other excipients including sucrose, hydroxy propyl methyl cellulose, magnesium carbonate, and
sodium lauryl sulfate have been prepared. Among different formulations, F14, which consists
of mannitol, sucrose, HPMC, talc, magnesium carbonate, and lansoprazole, is considered to be
the best formulation. Six other different formulations for the preparation of enteric coatings
based on Eudragit S100, Eudragit L100, triethyl citrate, and talc were prepared and coating
procedure on pellets (F14) was performed using coating pan.
 D.I. Wilson et al., 2010 studied to develop an extrusion–spheronisation (E–S) route to
manufacture pellets with a high loading (≥90 wt %) of 5-aminosalicylic acid (5-ASA).The
influence of the API chemical and physical properties on the rheological behavior of MCC-
based pastes undergoing extrusion was investigated. The performance as E–S aids of the
standard Avicel PH101 grade of MCC and of colloidal ones (i.e. Avicel RC591 and CL611),
alongside high loadings of 5-ASA, was also evaluated. Multi particulate E–S formulation
containing not less than 90 wt%5-ASA could be developed by combining an accordingly
micronized API and colloidal MCC grade.
 Simone Cristina Deo et al., 2011, studied to develop and evaluate a multi particulate
system consisting of pellets coated with polymer for pH-dependent release, derived from
methacrylic acid and incorporated into the tablet dosage form of mesalazine as a model drug.
The extrusion-spheronisation technique was used, resulting in smooth and spherical pellets with
uniform size distribution, which were coated in fluidized bed using Opadry Enteric 94K28327
containing Eudragit S100 as the agent regulating drug release. The dissolution profile of
coated pellets showed good control of drug release from the polymer at the two levels of
coating evaluated (8% and 10%), but only the 10% coated pellets were statistically similar to
Asalit 400 mg.

 M. S. Shetage et al., 2014, studied Drug loaded pellets are coated with pH
independent Eudragit RS100 and further coated with pH dependent Eudragit S100 in R and D
pan coater. Here different concentration of Drug coating Eudragit RS100 and further coated
with pH dependent Eudragit S100 in pan coater. The formulation was further characterized by
in vitro dissolution study, drug release kinetics and Micromeritic properties. coating level of
both the coats play a significant role in drug release property of which coating level of Eudragit
RS 100 was more significant after the tablet reaches colon optimized batch having 20% w/w
Eudragit RS 100 and 30% w/w with S100 as the drug release was below 20% in SIF so that it
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can be efficiently colon targeted, and the release is sustained up to 12 hrs which is desirable for
twice daily dosing of metoprolol.

 S. J. Kshirsagar et al., 2009, studied to develop the polymer coated diclofenac tablet
containing superdisintegrant for colonic drug delivery and compare the in vivo performance of
two polymers for site specificity. Eudragit FS 3D and Eudragit S100 were used as pH sensitive
polymers. Tablets were coated separately with Eudragit FS 30D and Eudragit S100 in various
thicknesses and evaluated for in vitro drug release using changing pH method In vitro release
studies reveals that Eudragit FS30D coated tablet with 10%w/w coating level start release of
drug at pH 6.8 after suitable lag time in the same pH which corresponds to colonic arrival time,
as compare to Eudragit S100 coated tablet which release only at higher pH, approximating the
transverse colon.
 Sanjay K. Jain et al., 2015 studied Eudragit S100 coated Citrus Pectin Nanoparticles (E-
CPNs) were prepared for the colon targeting of 5-Fluorouracil (5-FU). Citrus pectin also acts as
a ligand for galectin- 3 receptors that are over expressed on colorectal cancer cells. In vitro drug
release studies revealed selective drug release in the colonic region in the case of E-CPNs of
more than 70% after 24 h. In vitro cytoxicity assay (Sulphorhodamine B assay) was
performed against HT-29 cancer cells and exhibited
1.5 fold greater cytotoxicity potential of nanoparticles compared to 5-FU solution. In vivo data
clearly depicted that Eudragit S100 successfully guarded nanoparticles to reach the colonic
region wherein nanoparticles were taken up and showed drug release for an extended period of
time.
 Minjie sun et al., 2014, studied Preparation and evaluation of colon adhesive pellets of 5-
aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis. The core of the pellet was
formulated from bioadhesive agents, Carbomer 940 and Hydroxypropyl cellulose (HPC), by
Extrusion/Spheronization method and coated with Sureleaseas inner layer for waterproof and
with Eudragit1 S100 as outer layer for pH control. Microcrystalline cellulose 101(PH 301)
was found to be the best agent for pellet core. The ratio of CP940 to HPC should be kept as
(1:1) to achieve high bioadhesion. When the amount of Surelease was from 16% to 20% and of
Eudragit1 S100 was 28%, the dissolution profiles of coated pellets revealed no drug release in
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the artificial gastric fluid (pH 1.0) within 2 h and less than 10% was released in phosphate
buffer (pH 6.0) within 2 h whereas complete dissolution was observed in colonic fluid of pH
7.4 for 20 hrs.

 Raveendra M et al., 2012 studied to prepare floating microspheres of Timolol maleate

using Eudragit S 100 and Eudragit L 100 as polymer. Timolol maleate is non-steroidal anti-
inflammatory drug with short elimination half-life 1-3 hours. Floating microspheres of Timolol
maleate were set by emulsion solvent diffusion method using Eudragit S 100 and Eudragit L
100 as polymer. Formulation EU2 prepared with Eudragit S 100 drug polymer ratio
incorporation efficiency and percentage drug release 92.26 % for a period of 12 hrs.
 Sharma Madhu et al., 2012, studied the formulation of Mesalazine tablet with mixture of
Eudragit S-100 and L-100 as enteric coating. The core tablets of Mesalazine were ready for
using wet granulation containing a superdisintegrant. The plan of here study is to develop
colonic drug delivery of Mesalazine for ulcerative colitis using HPMC K-4M & HPMC K-15M
as a polymer. Results also establish that mixture of Eudragit S-100 and L-100 can be
effectively used to coat tablets for colon targeted release of drug.
 Vivek ranjansinhaet al., 2011, studied to found the effectiveness of a mixed film
composed of ethyl cellulose/Eudragit S100 for colonic delivery of 5-flourouracil (5-FU).
Tablets cores containing 5-FU were prepared by direct compression method by coating at
different levels with a non-aqueous solution containing ethyl cellulose/Eudragit S100. The
release was establish to be higher in tablets containing Avicel as filler owing to its wicking
action compare to that from lactose containing cores.

 Anuj Chawlaet al., 2015, studied the plan of the study was to get ready site specific drug
delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and
pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified
emulsification method followed by cross-linking with CaCl2, which was further coated with
the pH dependent polymer Eudragit S-100 to stop drug release in the upper gastrointestinal
tract. Furthermore, drug liberates from Eudragit S-100 coated microspheres follow the

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Korsmeyer-Peppas equation, representing 2 years shelf life of the formulation.

 Faizan Sayeed et al., 2014, studied The polymers used to in the time dependent part of the
release were HPMC and Ethyl cellulose with dissimilar ratios as the time with ethyl cellulose
increases due to its insoluble nature and this is reduced by the soluble nature of HPMC which
would give the coating layer some lipophilicity with which the release would be initiated for
the drug release. The coating of these two polymers is done by dry coating method. The enteric
coat over the time dependent polymer coat is to pass the dosage form from the stomach
which gives a two hours lag time.

 Akanksha Garud et al., 2013 studied to prepare, characterize and evaluate the colon-
targeted microspheres of mesalamine for the treatment and management of ulcerative colitis
(UC). Microspheres were prepared by the ionic-gelation emulsification method using
tripolyphosphate (TPP) as cross linking agent. The microspheres were coated with Eudragit S-
100 by the solvent evaporation technique to prevent drug release in the stomach. The release
profile of mesalamine from Eudragit- coated chitosan micro-spheres was found to be pH
dependent.
 Lorena Segale et al., 2016, studied formulation and the coating compositions of
biopolymeric pellets containing ranolazine were studied to improve their technological and
biopharmaceutical properties. Eudragit L100 (EU L100) and Eudragit L30 D-55-coated
alginate and alginate- hydroxypropylcellulose (HPC) pellets were prepared byionotropic
gelation using 3 concentrations of HPC (0.50%, 0.65%, and 1.00% wt/wt) and apply indifferent
percentages (5%, 10%, 20%, and 30% wt/wt) of coating material. The pellets containing 0.65%
of HPC and coated with 20% EU L100 represented the best formulation, able to limit the drug
release in acidic environment and to control it at pH 6.8.
 Dhiren Daslaniya et al., 2009, studied Mesalamine pellets were prepared by Coating drug
solution on sugar sphere followed by various functional coating. The influence of rate
controlling membrane made up of Eudragit RSPO and Eudragit RLPO in combination with
delay release polymer coating with Eudragit L100 in different proportions on drug release
kinetics was studied. Optimized formulation containing 796% drug loading on sugar sphere
followed by coated with Eudragit L100 (15%) and Eudragit RSPO & RLPO (10% in ratio of
7:3) were evaluated for In-vitro release profile. Prepared Pellets can be used in the treatment of

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the ulcerative colitis.

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