Chapter 3

Literature Review
3. LITERATURE REVIEW

1. Bulent Tutmez and A. Erhan Tercan [2006]

compared the performances of two

fuzzy modeling approaches such as Mamdani (linguistic) model and TakagiSugeno

(clustering based) model for spatial interpolation of rocks mechanical properties. To
achieve this purpose they used both data sets(simulated and measured). they considered
prediction error and data variability as performance criteria . In addition they used new
clustering validity approach for clustering-based modeling. In this article they indicate
that prediction performance of the clustering-based fuzzy modeling approach is higher
than that of the Mamdani model.

2. Candan Gokceoglu, Kivanc Zorlu [2003] conducted a series of rock mechanics test.
Following the tests they studies descriptive statistical on the parameters. They also
studied regression analyses and construction of fuzzy inference system. Simple
regression analyses didnt produce meaningful relations so multiple regression analyses
and the fuzzy inference system studied which exhibited good predictive performance.
They also studied the values account for (VAF) and the root mean square error indices to
check the prediction performance of the obtained models. As a result revealed that the
prediction performances of the fuzzy model are higher than those of multiple regression
equations

3. Saffet Yagiz , Candan Gokceoglu[2010] established dataset to estimate the rock

brittleness by constructing fuzzy inference system and nonlinear regression analysis by
utilizing the relevant laboratory rock tests at the Earth Mechanics Institute of Colorado
School of Mines in the USA on the rock samples assembled from 48 tunnels projects
throughout the world. They ran the established models than compared the performance
values such as RMSE, VAF, absolute error and coefficient of cross-correlation with
developed models. The VAF and RMSE indices were calculated as 89.8% and 2.97 for
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the nonlinear multiple regression model and 83.1% and 3.82 for fuzzy model,
respectively. By this paper they revealed that the prediction performance of the nonlinear
multiple regression model is higher than that of the fuzzy inference system model.
However they concluded that both constructed models exhibited a high performance
according to the obtained prediction values.
4. Jin Li, Andrew D. Heap [2013] provided guidelines and suggestions regarding
application of SIMs to environmental data by comparing the features of

non-

geostatistical interpolation methods, geo- statistical interpolation methods and combined

methods. They studied Factors affecting the performance like sampling design, sample
spatial distribution, data quality, correlation between primary and secondary variables,
and interaction among factors. They classified , quantified and clustered 25 commonly
applied methods based on their features to provide an overview and similarities of the
relationships among them at the and they developed an easy to use decision tree for
selecting an appropriate method from these 25 methods is developed based on data
availability, data nature, expected estimation, and features of the method. .
5.T.Y. Puttewar et al., [2010] have developed Doxilamineorodispersible tablets with
considerable increase in drug release as compared to marketed formulations, seven
formulations were developed and studied. The difference in drug release values was
found to be 100.45 1.89 and 56.47 1.89, respectively. To prevent bitter taste and
unacceptable odour of the drug, the drug was taste masked with weak cation exchange
resins like Indion 234, Indion 204 and Indion 414. The drug was characterized according
to different compendial methods, on the basis of identification by UV spectroscopy, pH,
organoleptic properties and other tests. Among the three resins, one was selected for
further studies i.e., Indion 234, because of high drug loading capacity. Drugresin
complex was prepared using batch method and effect of various processing parameters
viz. drugresin ratio, pH, temperature and drug concentration was studied to optimize the
loading conditions. Maximum loading was obtained at drugresin ratio 1:2, pH 5,
temperature 50 _C and drug concentration 4 mg/ml. A successful taste masking of
resinate was confirmed by time intensity method and also by taking drug release in 0.01
N hydrochloric acid and in simulated salivary fluid. The values of pre-compression
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parameters evaluated, were within prescribed limits and indicated good free flowing
properties. The data obtained of post-compression parameters such as weight variation,
hardness, friability, wetting time, water absorption ratio, content uniformity,
disintegration time and dissolution and was found superior over conventional
formulation. The F5 batch with disintegration time 25.24 0.75 and dissolution 100.46%
3.78 was selected as optimized formulation. This was compared with conventional
marketed formulation and was found superior. Batch F5 was also subjected to stability
studies for three months and was tested for its disintegration time, drug contents and
dissolution behaviour monthly. It was observed that the contents of the tablets remained
the same. By an appropriate selection and combination of excipients it was possible to
obtain orodispersible and taste masked tablets.8
6. Ashwini R. Madgulkar et al., [2009] have prepared novel taste masked mouthdissolving tablets of tramadol that overcomes principle drawback of such formulation
which is inadequate mechanical strength. In this work, the bitter taste of Tramadol HCl
was masked by forming a complex with an ion exchange resin Tulsion335. The novel
combination of a superdisintegrant and a binder that melts near the body temperature was
used to formulate mechanically strong tablets that showed fast disintegration. A 32 full
factorial design and statistical models were applied to optimize the effect of two factors,
i.e., superdisintegrant (crospovidone) and a mouth-melting binder (Gelucire 39/01). It
was observed that the responses, i.e., disintegration time and percent friability were
affected by both the factors. The statistical models were validated and can be successfully
used to prepare optimized taste masked mouth-dissolving tablets of Tramadol HCl with
adequate mechanical strength and rapid disintegration.9
7. Dionysios Dennis Douroumis et al., [2011] have mask the taste of cetirizine HCl and
incorporate the granules produced in oral disintegrating tablets (ODT). The bitter, active
substance was coated by fluidized bed coating using Eudragit RL30-D at levels
between 15% and 40% w/w. The ODTs were developed by varying the ratio of
superdisintegrants such as sodium croscarmellose, crospovidone grades and low
substituted hydroxypropyl cellulose (L-HPC). A direct compression process was used to
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compress the ODTs under various compaction forces to optimize tablet robustness. The
properties of the compressed tablets including porosity, hardness, friability and
dissolution profiles were further investigated. The in vitro and in vivo evaluation of the
tablet disintegration times showed almost identical rapid disintegration below 10 s at the
optimal levels of each superdisintegrant. Finally, the taste and sensory evaluation in
human volunteers demonstrated excellence in masking the bitter active andtablet
palatability.10
8. Adamo Fini et al., [2007] have prepared Eight formulations containing ibuprofen in
the form of orally disintegrating tablets. To prevent bitter taste and side effects of the
drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet
granulation. The granules were then coated using different film forming agents (Kollicoat
SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 14. Coated
granules were then formulated with a sweetener (Aspartame), a mannitol-based diluent
(Pearlitol SD 200) and Kollidon CL (1-4K) or Explotab (1-4E) were added as
superdisintegrants and compacted under low compression force. The eight lots of tablets,
1-4K and 1-4E, were assessed if suitable as oral disintegrating tablets by determination of
a range of technological parameters. Wetting and disintegregation time matched with the
requirements of EP IV Ed., for almost all these formulations. Dissolution profiles
suggested that the combined action of the hydrophobic lecithin and the coating delay the
release of the drug from tablets with respect to when it is free or in the form of simple
granules. By an appropriate combination of excipients it was thus possible to obtain
orally disintegrating tablets and a delayed release of ibuprofen using simple and
conventional techniques.11
9. Devireddy SR et al., [2009] have developed
levocetirizine dihydrochloride

Orally disintegrating tablets of

with different superdisintegrants (sodium starch

glycollate, croscarmellose sodium, and crospovidone) using mannitol as a diluent.

Tulsion-335, Indion-204, and poly kyron T-134 cation exchange resins were used as
taste-masking agents. The drug and resin complex was prepared by the kneading method.
Ten formulations were prepared with varying combinations of superdisintegrants and ionDEPATRMENT OF PHARMACEUTICS

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exchange resins by the wet granulation technique, using polyvinylpyrrolidone K-30 as the
binder. The prepared tablets were evaluated for degree of taste masking, weight variation,
hardness, friability, in vitro and in vivo disintegration time, content uniformity, and water
absorption ratio. Dissolution studies were performed in two dissolution media: 0.1N HCl
and distilled water. The corresponding dissolution rates were compared with the marketed
formulation. Differential scanning calorimetry studies were carried out on the drug-resin
complexes. Prepared tablets were good in appearance and showed acceptable results for
hardness and friability. In vitro and in vivo disintegration times for the optimum
formulation (F-1) were found to be 22 and 55 s, respectively. Relatively acceptable taste
was achieved with both Indion-204 and Tulsion-335. Rapid disintegration time was
achieved in tablets containing crosspovidone as the superdisintegrant. Dissolution studies
indicated the formation of the complex of drug and resin. Differential scanning
calorimetry studies indicated the formation of drug-resin complex.12
10. Mowafaq M. Ghareeb et al., [2009] have aimed to enhance the dissolution rate of
meloxicam (MLX), a practically water-insoluble drug by preparation of solid dispersion
using a hydrophilic polymer, poloxamer 188 (PXM). The kneading technique was used to
prepare solid dispersions. A 32 full factorial design approach was used for optimization
wherein the drug, polymer ratio (X1), and the kneading time (X2) were selected as
independent variables and the dissolution efficiency at 60 min (%DE60) and yield
percent were selected as the dependent variable. Multiple linear regression analysis
revealed that for obtaining higher dissolution of MLX from PXM solid dispersions, a
high level of X1 and a high level of X2 were suitable. The use of a factorial design
approach helped in optimization of the preparation and formulation of solid dispersion.
The optimized formula was characterized by solubility studies, angle of repose, and
contact angle; Fourier transform infrared spectroscopy, differential scanning calorimetry,
x-ray diffraction studies, and scanning electron microscopy demonstrated that enhanced
dissolution of MLX from solid dispersion might be due to a decrease in the crystallinity
of MLX and PXM. Analysis of dissolution data of optimized formula indicated the best
fitting with Korsemeyer Peppas model and the drug release kinetics as Fickian diffusion.

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In conclusion, dissolution enhancement of MLX was obtained by preparing its solid

dispersion with PXM using kneading technique.13
11. Debajyoti ray et al., [2010] have developed the

floating tablet of Tramadol

Hydrochloride (TH). Floating delivery system of TH was prepared using different grades
of HPMC as drug release retarding polymer and sodium bicarbonate as source for carbon
dioxide which helps tablets to float. From FTIR studies no interactions were found
between TH and polymers. The flow properties of the granules were studied and
formulation F5 was found to have comparatively good compressibility index and hausner
ratio than other formulations. From the swelling study of the formulations, formulation
F5 was found to have good swelling properties (220%). From the dissolution studies of
the formulations, formulation F5 was found to have better drug release profile than other
formulations. From the drug release kinetic study, Higuchi model was found to be best
fit. So it could be predicted that release of TH from the floating drug delivery
formulations were of diffusion type.14
12. Gohel et al., [2004] have developed mouth dissolving tablets of Nimesulide.
Granules containing Nimesulide, Camphor, Crospovidone, and lactose were prepared by
wet granulation technique. Camphor was sublimed from the dried granules by exposure
to vacuum. The porous granules were then compressed. Alternatively, tablets were first
prepared and later exposed to vacuum. The tablets were evaluated for percentage
2
friability, wetting time, and disintegration time. A 3 full factorial design was used to
investigate the joint influence of 2 formulation variables: amount of camphor and
crospovidone. The results shows that sublimation of camphor from tablets resulted in
superior tablets as compared with the tablets prepared from granules that were
exposed to vacuum. The systematic formulation approach helped inunderstanding the
effect of formulation processing variables.15
13. Nagendrakumar et al., [2009] have developed fast dissolving tablets of Granisetron
Hydrochloride using novel co-processed superdisintegrants consisting of crospovidone
and Crosscarmellose sodium in the different ratios (1:1, 1:2 & 1:3). The developed
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superdisintegrants were evaluated for angle of repose, Carrs index and Hausners ratio
in comparison with physical mixture of superdisintegrants. The angle of repose of the
developed excipients was found to be < 25, Carrs index in the range of 10-15% and
Hausners ratio in the range of 1.11 to 1.14. Fast dissolving tablets of granisetron
hydrochloride were

prepared using the above co-processed superdisintegrants and

evaluated for pre-compression and post-compression parameters. Based on in-vitro

dispersion time (approximately 20 sec), promising formulation CP1 was tested for
in-vitro drug release pattern in pH 6.8 Phosphate buffer and short-term stability (at 40
C / 75% RH for 3 months), drug excipients interaction (IR spectroscopy) were studied.
Among the designed formulations, the formulation containing 4% w/w of co-processed
superdisintegrant (1:1 mixture of crospovidone and croscarmellose sodium ) emerged as
the overall best formulation (t50% 3.0 min) based on drug release characteristics in
pH 6.8 phosphate buffer compared to commercial conventional tablet formulation
(t50% >15 min). Short-term stability studies on promising formulation indicated that
there were no significant changes in drug content and in-vitro dispersion time (p <
0.05).16
14. Preetha et al., [2008] have studied the effect of mode of incorporation of
superdisintegrants

like

Croscarmellose

sodium,

Sodium

starch

glycolate

and

Crospovidone (polyplasdone XL and XL-10) on dissolution of three model drugs with

varying aqueous solubility, like Carbamazepine (poorly soluble), Acetaminophen
(sparingly soluble) and Cetrizine Hydrochloride (soluble) from their respective tablet
formulations prepared by wet granulation was studied. The disintegrants were
incorporated extragranularly or intragranularly or distributed equally between the two
phases. The results indicated that Crospovidone in general was effective in improving the
dissolution of the drugs used in the study and generally extragranular mode of addition
seemed to be the best mode of incorporation, irrespective of the solubility of the main
tablet component.17
15. Yi-Dong Yan et al [2010] have prepared and evaluate a non-bitter donepezil
hydrochloride (DH) orally disintegrating tablet (ODT) for enhanced patient compliance.
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Taste masking was done by preparing micro- spheres with different ratios of drug and
Eudragit

EPO using spray drying method. The entrapment of the drug into

microspheres was conrmed by scanning electron microscope (SEM) and X-ray powder
diffraction. It was found that microspheres with a drugpolymer ratio of 1 : 2 could
mask the taste obviously by inhibiting the release of DH in simulated salivary uid.
Microspheres-loaded tablets containing Polyplasdone NF and Low sub- stituted
Hydroxypropyl Cellulose (L-HPC) both at a 10% level showed rapid disintegration, in
vitro (15.5 s) and in vivo (19.8 s), which were faster than that of marketed tablets (36.7,
41.3 s, respectively). Results from taste eval- uation in human volunteers revealed that
the ODTs with taste-masked microspheres had signicantly enhanced palatability.
Dissolution in vitro and pharmacokinetics in rats were evaluated for the tested ODTs
compared to the donepezil hydrochloride commercial product (ARICEPT). Both tablets
showed comparable dissolution pat- terns in vitro and similar area under curve from 0 to
24 h (AUC024), Cmax and Tmax of DH in vivo to each other, suggesting that the
tested ODTs might give the similar drug efcacy in rats compared to that of ARICEPT.
Thus, it was concluded that DH ODTs with masked taste were obtained by Eudragit
EPO-based microspheres, drug loaded microspheres neither decreased the bioavailability
nor delayed the release of DH.18
16. Punit P Shah et al [2007] have masked the intensely bitter taste of artemether
(ARM) and to formulate a rapid-disintegrating tablet (RDT) of the taste-masked drug.
Taste masking was done by solid dispersion with mono amino glycyrrhyzinate
pentahydrate (GLY) by solvent evaporation method. To characterize and formulate taste
masked rapid disintegrating tablets (RDTs) of ARM, the 1:1M solid dispersion was
selected based on bitterness score. Fourier transform infrared spectroscopy (FTIR),
differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were
performed to identify the physicochemical interaction between drug and carrier, hence its
effect on dissolution. RDTs were evaluated for weight variation, disintegration time,
hardness and friability. In vitro drug release studies were performed for RDTs at pH 1.2
and 6.8. Bitterness score was evaluated using mini-column method and compared with
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gustatory sensation test. FTIR spectroscopy and DSC showed no interaction while XRPD
showed amorphization of ARM in GLY solid dispersion. RDTs prepared using solid
dispersion, (RDT3), showed faster disintegration (within 28 s) and complete bitter taste
masking of ARM. In addition, RDT3 exhibited better dissolution profile at both pH 1.2
and 6.8, than RDTs prepared from pure ARM (RDT5). Taste evaluation of RDTs in
human volunteers rated tasteless with a score of 0 to RDT3 and 3 to RDT5. Mini-column
revealed that RDT5 showed increase in number of persons who sensed bitterness with
increased amount of ARM release while RDT3 sensed no bitterness. Thus, results
conclusively demonstrated successful masking of taste and rapid disintegration of the
formulated tablets in the oral cavity with improved dissolution.19

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