WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Virag et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 2.786

Volume 4, Issue 1, 477-493. Review Article ISSN 2278 – 4357

APPLICATIONS OF BIOINFORMATICS IN PHARMACEUTICAL

PRODUCT DESIGNING: A REVIEW

Virag A. Shah*, Deepika N. Rathod, Tarashankar Basuri, Vishal S. Modi,

Ishvar J. Parmar

SSR College of Pharmacy, Silvassa, U.T of Dadra & Nagar Haveli-396230.

ABSTRACT
Article Received on
19 Oct 2014, Bioinformatics is the very fast emerging field in our pharmaceutical
Revised on 14 Nov 2014, industries. The field was widely used in other branches like
Accepted on 10 Dec 2014
biotechnology, biology and many other fields and nowadays finding a
wide application in the pharmacy field. The work describes different
*Correspondence for aspects related to application of computers in drug designing,
Author discovery and development, formulation designing. Bioinformatics is
Virag A. Shah
the combination of computers, databases, statistics, graphs and 3-d
SSR College of Pharmacy,
Silvassa, U.T of Dadra &
plots make the big problem of designing the new formulation of a total
Nagar Haveli-396230. new molecule is the most interesting aspect of this field in the
pharmaceutical field. Optimization process which helps to reduce the
number of experiment to be conducted and help the research scientist. Also bioinformatics
helps to link the information obtain from different field. The different software’s like design-
ease, stat-ease, design-expert etc. are available for all the aspects in designing the formulation
makes the costly and time consuming process very easy, fast and cost effective.

KEYWORDS: Bioinformatics, optimization, stat-ease, design-expert.

1. INTRODUCTION [1, 2]
Bioinformatics is the branch which deals with the application of computer technology for the
management and analysis of the biological information. Bioinformatics is the rising sun in the
global as well as for Indian pharma sector. These rising sun can produce immense economic
heat for the growth of the Indian pharma sector. It is being an interface between the modern
biology and informatics which is involved in discovery, development and implementation of
biological processes with the goal to serve and help in healthcare sector. In the
pharmaceutical sector, it can be used to reduce the time, cost and make the people understand

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the complex mathematical and statistical equation in simple and easily readable form in order
to facilitate drug discovery, drug development and product development at a faster rate.

Some of the important pharmaceutical areas and the utility of bioinformatics technology are
given as follows
1. Drug discovery, designing and development
2. Product/Formulation designing
3. Polymer modeling
4. Pharmacology

1. Drug Discovery, Designing and Development

Only 10% of the drug molecules which are identified in research area make through the drug
development phase. This means that many of the potential drugs do not make it to market,
and expensive time and resources which has been invested suffer a heavy loose without
generating any capital. Simulation and informatics can significantly help in improving the
efficiency of drug development, cutting costs, and improving margins. There are many
bioinformatics resources which are growing importance to understand and predict absorption,
distribution, metabolism, excretion and toxicity of both existing drugs and potential drug
leads.

2. Product/Formulation Designing
Formulation is the process of mixing of ingredients in such a way as to produce a new or
improved product. The formulation department must balance the different marketing and
deliverability requirement with chemical constraints and cost to come up with the best
possible drug delivery method at the best price. The information regarding the number of
batches which are formulated in the designing process will be stored in the corporate database
which will help the scientist to access the results and methods from anywhere in the world.
They can use their time and resources on new research, rather than repeating the old work.
Also with the aid of optimization software’s the best formulation can be obtained by using
the data of the previously formulated batches.

3. Polymer Modeling
Many of the drug delivery devices are polymeric with drug either solubilized or emulsified in
the polymer. These drug delivery system have a mesoscale structure; between 10 to 1000 nm.
The amount of computing power required to model these systems at an atomistic level is

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prohibitive, and macroscale techniques such as Finite element analysis or computational fluid
dynamics do not give the required level of detail. Mesoscale modeling, focusing on the
nanometer length scale, is helping scientists to develop colloidal delivery systems for drugs.
Achieving a suitable formulation of the drug candidate can determine the rate at which a drug
gains FDA approval. Techniques such as polymer modeling are helping to create new
methods of drug delivery.

4. Pharmacology
Bioinformatics is used in drug target identification and validation and in the development of
biomarkers and toxicogenomic and pharmacogenomic tools to maximize the therapeutic
benefit of drugs.

1.1 Importance of Bioinformatics [3]

Bioinformatics focuses on two main areas: Data Management and Data Analysis, which find
application in
a) Helping scientists or researchers in fast research.
b) Leading to quick inventions by providing readily available information with the help of
computer technology.
c) In interlinking information from different fields and leads to quick results.
d) In designing information available on paper or in the form of specimen.

2. Optimization Techniques in Pharmaceutical Industry [4, 5]

Optimization techniques are abundant in pharmaceutical industry. These methods find
themselves in an intermediate position between the strong methods, and weak methods.
Optimization refers to the art and science of allocating available resources to the best possible
effect. In other words it is the search for a maximum or minimum in the value of a certain
response function.

In optimization we basically have two common terms: 1. Factor and 2. Response

Example: For the formulation of tablets we need API and excipients, the different excipients
like binder, polymer, disintegrant, glidant etc are used in different proportion. These N
numbers of excipients are considered as factors and by their interaction in the formulation
what we get is called as response.

2.2 Applications

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a) Used to design the best formulation.

b) Used in industrial planning, allocation, scheduling, decision-making, etc.
c) Used for analysis of formulations.
Many different optimization methods exist and they can be classified in a number of ways.

2.3 Classification
The optimization techniques thus formulated can be classified as conventional and recent
based on the type of objective and constraint.

Conventional Optimization Techniques

a) Hybrid method
b) Monte carlo simulated annealing
c) Random search.

Recent Optimization Techniques

a) Factorial design and optimization
b) Global optimization
c) Artificial neural network.

2.4 Role and Application in Supporting Formulation Development

This optimization shortens the development time of any formulation.
Further it simplifies the formulation.
Mostly widely employed for formulating tablets and capsules
The references of the work done serves as the teaching tools for the further researchers by
formulating and preserving knowledge and experience of experts.

Limitations
The only limitation of this technique is that as it involves and works only with situations that
have been anticipated in programs.

3. Introduction to Various Software’s [6, 7, 8]

Statistical methods are becoming increasingly important for the pharmaceutical industry. The
FDA and other regulatory and standard-setting organizations are moving swiftly for the
establishment of Quality by Design (QbD) guidance relevant to the needs of pharmaceutical
manufacturing.
3.1 Design of Experiments (DOE)

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The FDA suggests the use of design of experiments (DOE) because ―it provides a structured,
organized method for determining the relationship between factors affecting a process and the
response of that process.‖

While it is possible to perform DOE with general statistical software, most users in the
pharmaceutical industry look for software designed especially for DOE because it is
generally much easier for non-statisticians to use.

3.1.1 Significance/Features of DOE

DOE is used to determine the impact of multiple factors and their interaction. Finally scale-
up correlation is used to translate operating conditions between different scales or types of
equipments.

Compared to the traditional trial and error method or the method of considering one factor at
a time (OFAT) DOE drastically reduces the number of runs required to determine the optimal
value of each factor. This approach determines not just the main effects of each factor but
also the interactions between the factors, which is often the key to big breakthroughs.

The software prompt the users to enter the factors and responses and select the type of
experiment while providing information that will help the user pick the best type. The
software then generates a randomized list of experimental runs. As each run is completed in
the order given, the results are entered into the software. The software then generates tabular
and graphical data that helps define the region where quality product is produced.

DOE software enables the user to easily choose from a range of experimental designs. For
example, mixture experiments are useful in many pharmaceutical applications. A typical
mixture experiment might be used to investigate the effect of changing the proportions of
polymer, drug and three excipients on four responses in a sustained release tablet based on a
hydrophilic polymer.

DOE software makes it easy to define the design space by entering low and high values for
components. In the case of the mixture experiment mentioned above we will define the limits
of the components for hydrophilic tablet mixture design as shown in the table below.

Table 1: Limits of the Component of Hydrophilic Tablet Mixture Design

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Name low High

Lactose 5 42
Phosphate 5 47
Cellulose 5 52
Polymer 17 25
Drug 1 2
Total = 100wt%

The software automatically set up the experimental design. In this case, we will assume that a
quadratic polynomial, which includes second order terms for curvature, will adequately
model the responses. We can pick
a) 15 model points using the optimality criteria
b) 5 lack of fit points using distance as the criteria
c) 5 replicate using the optimality criteria.

There are four responses

Table 2: Table Showing Four Responses
Name Units
T (50%) H
Shape Factor
Hardness Kp
Friability %
The software automatically designs an experiment with 25 runs as shown in the table below.

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DOE software typically allows for five possible goals in constructing an index of desirability
maximum, minimize, target, in range and equal to. Desirability ranges from zero to one for
any given response. The program will combine individual desirability into a single number
and then search for the greatest overall desirability. A value of 1 provides the ideal case. For
example, in the chart below, the desirability of T (50%) is 1 at a value of 8 and the
desirability ramps down to 0 as it moves from the target value to the low and high values of 6
and 10 respectively.

Table 3: Desirability of Target from High Value to Low Value.

Response Goal Low High
T (50%) Target=8 6 10
Shape Minimize 6 1.5
Hardness Target=6 4 9
Friability Minimize 1 2

Now we can optimize the model using the criteria shown in the table above for two drug
dosages: regular strength = 1 wt% and extra strength at 2 wt%.

Figure 1: Doe Software Maps Out Design Space.

The chart above shows the optimized values for each factor superimposed on an overlay plot
of the factors analyzed in the study. The overlay window shows the design space which
indicates the various combinations of the factors that will provide results within the
acceptable range. Further from this the framing of design space to account for confidence
prediction and tolerance intervals.

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Figure 2: Design Space Framed With Confidence Intervals.

The latest generation of DOE software helps simplify QbD studies by overlaying confidence,
prediction and tolerance intervals with configurable colors onto one-factor response plots.
These intervals frame the design space which makes it easier to ensure that the design space
is never violated. This accelerates the potential of DOE software to comply with FDA
requirements.

3.2 Factorial Experimental Design Software [9, 10]

Two or independent variables (factors) are tested at different level. All the factors are
combined to each other at all levels. For eg.32 full factorial design has 9 experiments. 42 full
factorial designs have 16 experiments. Factorial experimental design software drastically
simplifies previously laborious hand calculations needed before the use of computers. These
designs can be quite compact, involving as few as two levels of each factor and only a
fraction of all the combinations, and yet they are quite powerful for screening purposes.
During World War II, a more sophisticated form of DOE, called factorial design, became a
big weapon for speeding up industrial development for the Allied forces. After the war,
statistician at Imperial Chemical George described how to generate responses for process of
optimization. From this point forward, DOE took hold in the chemical process industry,
where factors such as time, temperature, pressure, concentration, flow rate and agitation are
easily manipulated.

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3.3 Design-Ease
After the factorial experimental design software later, Box co-authored a textbook that
formed the basis for the original version of DOE software by Stat-Ease, Inc., called Design-
Ease. As design of experiments software advancements gave rise to solving complex factorial
statistical equations, statisticians began in earnest to design experiments with more than one
factor (multifactorial components) being tested at a time. Simply stated, computerized multi-
component design of experiments began supplanting one-factor-at-a-time experiments.
Computer software designed specifically for designed experiments became a commercial
reality in the 1980s—available from various leading software companies such as the
aforementioned Design-Ease JMP and Minitab.

Notable benefits when using design of experiments software include avoiding laborious hand
calculations when:
1. Identifying key factors for process or product improvements.
2. Setting up and analyzing general factorial two-level factorial, fractional factorial (up to 31
variables) and Plackett Burman designs (up to 31 variables).
3. Performing numerical optimization.
4. Screening for critical factors and their interactions.
5. Analyzing process factors or mixture components.
6. Combining mixture and process variables in designs.
7. Rotating 3D plots to visualize response surface.
8. Exploring 2D contours with a computer mouse, setting flags along the way to identify
coordinates and predict responses.
9. Precisely locating where all specified requirements meet using numerical optimization
functions within DOE software.
10. Finding the most desirable factor settings for multiple responses simultaneously.

Today, factorial DOE software is a notable tool that engineers, scientists, geneticists,
biologists, and virtually all other experimenters and creators, Design of experiments software
is therefore a valuable tool with broad applications in almost each and every aspect.

3.4 Design-Ease Software

Identify the breakthrough factors for process or product improvement. Design-Ease software
helps you set up and analyze general factorial, two-level factorial, fractional factorial (up to
31 variables) and Plackett-Burman designs (up to 31 variables). With these designs you can

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quickly screen for critical factors and their interactions. You can also do numerical
optimization.

Figure 3: 2-level factorial design.

3.5 Stat-Ease® DOE Software [11]

Helps when we are designing a new product or process, or improving your current one, Stat-
Ease makes it easy with statistical design of experiments (DOE) software. We can use
Design-Expert® or Design-Ease® software to save money, save time, and increase quality.
Design-Ease offers multilevel factorial screening designs to help you find the critical factors
that lead to breakthrough improvements. Display optimum performance with colorful 3D
plots.

3.6 Designs-Expert Software

Design-Expert is a comprehensive DOE tool with all of the features of Design-Ease, plus
much more. It appeared in early 1970s. The performance of this software’s reaches the level
of a human expert so the name expert is given. It Combine mixture and process variables in
the designs. Design-Expert offers rotatable 3D plots to help you visualize your response
surface. Explore the 2D contours with your mouse, setting flags along the way to identify
coordinates and predict responses. The sweet spot where all your requirements are met can be

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found via the program's numerical optimization function, which finds the most desirable
factor settings for multiple responses simultaneously.

Figure 4: 3d plot to visualize response surface.

3.7 KinetDS: Open Source Software for Dissolution Test Data Analysis [12]
As drug quality is the focus for pharmaceutical industry and regulatory agencies, the in vitro
dissolution test becomes a standard tool for characterization of manufactured products.
However, results of the dissolution test must be expressed in mathematical terms; this is
realized by fitting various models to the cumulative dissolution curves. The fitting process
requires software (e.g., KinetDS) for automation and determination of possible release
mechanisms of drug substances from the dosage forms. The software is FOSS (Free Open
Source Software).

KinetDS is software for curve fitting, designed particularly to describe the cumulative
dissolution curve by a simple equation or set of equations. However, other curves, derived
from different data sources, might be also analyzed if their dependent-variable range is
between 0 and 100. The equations were chosen from the most popular mechanistic and
empirical models applied to the drug dissolution curve description such as zero- to third-order
kinetic models, Higuchi, Koresmeyer–Peppas, Weibull, Hixson–Crowell, Michaelis–Menten,

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and Hill equation. All the models included in KinetDS 3.0 are susceptible to linearization.
Therefore, they might be fit by both linear regression and NLR.

3.8 Tablet Dissolution Testing Data Management Software [13]

Icalis Data Systems Ltd is a UK company, established in 1988, whose business focus is
professional data management software systems which integrate and automate laboratory
instruments to deliver unique final solutions. The company’s current main product is its
Tablet Dissolution software that is marketed worldwide by Icalis and its Distributors. Many
of the world’s largest pharmaceutical companies such as GSK, Novartis, Pfizer AstraZeneca,
Elan and Solvay etc., have multiple installations of the IDIS EE dissolution software.

Applications for a wider chemistry discipline are already planned as well as other
instrumentation.

4. Research and Applications of Bioinformatics

Collaboration Potential
Fundamental changes have happened in major pharmaceutical organizations in the way they
use bioinformatics for their research and their perspective on outsourcing.

GSK for example, has reduced resource from 250-300 people in bioinformatics to 25-30 now
(Jan 2012). The change was predominantly to absolutely focus on applications, and not on
research. Furthermore the trend towards outsourcing within the Drug Discovery phase of
large Pharma companies is currently at levels of approximately 40-50% in Eli Lilly, slightly
more in GSK and approx 30% in AZ chemistry (though less in their biology section). This is
expected to increase over the coming 5 years.

The $8bn market for Pharma research breaks down as $6bn in hit finding phase of R&D and
then $2bn on lead exploitation including focused combinatorial chemistry libraries, medicinal
chemistry compound creation and testing within secondary screens.

Therefore there is clearly a growing need and opportunity for contract services within the
field of Bioinformatics and related sciences.

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Table 4: Research Field and Work Conducting Institute.

Research Institute/University/Group/Unit Description
Field Name
Drug Design The Centre for Drug Research (CDR) It is a multidisciplinary research
in Helsinki University has groups: centre that focuses in the fields of
for example drug discovery tools and
pharmaceutical nanotechnology
Computational Pharmaceutical group
Applying computational
modeling tools to pharmaceutical
Computational Drug Discovery group nanotechnology

Modeling of protein-ligand
complexes, especial focus on G-
protein coupled receptors
Drug Design and Synthesis Laboratory, Applying drug design tools
University of Eastern Finland at
Kuopio
Cell and Molecular Biology (CBL), Aiming to increase the
Jyvaskyla University knowledge on ligand recognition
of proteins, and discover novel
protein subtype selective ligand

Industrial Representatives
Bioinformatics for traditional Pharmaceutical Research
Bioinformation technology is mostly found in the biotech and pharmaceutical industries or
related service companies. Finland has pharmaceutical company such as Orion who has
strong internal bioinformatics knowledge and groups. Smaller drug discovery companies
have limited resources for bioinformatics and they usually outsource these activities.
There are several service companies who provide bioinformatics services, at least as part of
their service portfolio. These include, for example companies such as
a) SBW Ltd. (www.sbw.fi)
b) GenoSyst Ltd.(www.genosyst.com)
c) Xemet Ltd. (www.xemet.com)
d) Euformatics (www.euformatics.com)
e) BCPlatforms (www.bcplatforms.com)
f) Triacle Biocomputing (www.triacle-bc.com)
g) Genevia Technologies (www.genevia.fi)
h) Statfinn (www.statfinn.fi)
i) BiOptima (www.bioptima.fi)
j) 4Pharma Ltd. (www.4pharma.com)

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Developmental Opportunities
In Bioinformatics, the real long-term value for pharmaceutical companies lies in converting
the data into useful therapeutics and hence efforts are on to make the bioinformatics tools as
standardized and easy as possible, which is somewhat similar to the development of
standardized computer operating systems. The challenge facing bioinformatics researchers is
simply making sense of the plethora of genomic data, finding out how all the shards of
information relate to one another, while constantly refining their technology and research
approaches. Such challenges drive opportunities for development and innovation, a large part
depending on the integration of databases across functions and across companies, as well as
on ensuring such development can be delivered and used appropriately by scientists with no
bioinformatics background.

Development opportunities are also in related life science areas where still low-level use of
Bioinformatics occurs, like cosmetics (e.g. based on understanding of human dermatology
work), clinical trials (handling of large data sets and data searching techniques) and
diagnostics (Companion Animal Health diagnostics in particular).

Examples were bioinformatics has been utilized

1. Discovering Novel Carriers for Oral Insulin Tablets: a Pharmacoinformatics
Approach [14]
Insulin is used medically to treat Type 1 diabetes mellitus most commonly injected
subcutaneously for human beings. The realization that insulin injections have become a part
of life can be extremely harrowing for many diabetic patients. Using insulin therapeutically is
not a new practice, but still delivery methods to make the process more bearable have not
gained widespread prominence as of yet. Oral delivery of insulin in tablet form has always
been a significant challenge for pharmaceutical researchers. This study is a prospect of oral
insulin tablet through pharmacoinformatics approach.

2. Meropenem: a Potent Drug Against Superbug as Unveiled Through Bioinformatics

Approaches [15]
Global spread of multi-drug resistant bacteria like Klebsiella pneumonia and Escherichia coli
have raised the alarm for researchers and doctors throughout the world. This new mechanism
of resistance and the ability of ndm-1 gene to be transferred between the species may end the
era of antibiotics treatment. Carbapenems are reliable drugs against many multi-resistant
gram-negative pathogens. A 3-D homology model of NDM-1 was built and analyzed for

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elucidation of functional site and binding interactions. This study revealed that meropenem
has good interaction with the active sites of the receptor that could retard the spread of
antibiotic resistant bacteria.

3. Receptor-Based Pharmacophore Tool for Design and Development of Next-

Generation Drugs [16]
Drug discovery is a vast field in which scientists search to find a suitable drug for a target
protein to alter its function in a required manner. A Pharmacophore is an essential ensemble
of steric and electronic features for drug discovery, which is necessary to ensure the optimal
interactions with a specific target structure and to trigger its biological response. The
proposed tool serves as a molecular visualization tool to familiarize the user with the existing
classes, as a means to create a transparent sphere for a user-friendly GUI, as a way to
implement newly developed algorithms and as a means of Pharmacophore generation through
3D computational tools and Java programming for better understanding in areas such as 3D
geometry, pharma-research and bio-informatics. Receptor-Based Pharmacophoric Tool
(RBPT) designing is an innovative approach in drug discovery for generating
pharmacophores using the structure of the target protein at the specified binding site. The
pharmacophores generated for the specified binding site of a target can be used in virtual
screening and to find the set of ligand that show considerable activity. RBPT is intended to
serve the scientific community working in the areas of drug design, development and
discovery.

4. Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast

Cancer Using Sparse Logistic Regression [17]
Sparse Logistic Regression (SLR) was utilized to build two sparse and interpretable
predictors. The first one (SLR-65) was based on a signature consisted of the top 65 probe sets
(59 genes) differentially expressed between pathologic complete response (pCR) and residual
disease (RD) cases, and the second one (SLR-Notch) was based on the genes involved in the
Notch singling related pathways (113 genes). The two predictors produced better predictions
than the predictor in a previous study. The SLR-65 selected 16 informative genes and the
SLR-Notch selected 12 informative genes.

CONCLUSION

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Bioinformatics is very fast emerging and finding a greater application of pharmaceutical

field. Bioinformatics reduces all the overall capital used for product designing both
financially and manually and gives the best results in a most effective way. The use of
different software’s has made a large work in to a compact form and implementing them in
optimization techniques which is a novel approach towards product designing. This
software’s has made all the laborious tasks so easy that the crores and crores of investment in
designing the formulation has drastically being reduced. This is expected to be more booms
and exploiting in coming years in the pharmacy field, helping the pharma industry to grow.

REFERENCES
1. Luscombe NM, Greenbaum D and Gerstein M. What is Bioinformatics? A Proposed
Definition and Overview of the Field, Journal of Information in Medicine, 2001; 40(4):
346-58.
2. Mallick B, Ghosh Z. Bioinformatics - the rising sun. Indian science cruiser, 2006; 20(1):
44-50.
3. Box GEP and Wilson KB. On the Experimental Attainment of Optimum Conditions.
Journal of the Royal Statistical Society. Series B, 1951; 13:1-45.
4. Augsburger LL, Hoag SW. Pharmaceutical dosage forms: tablets, 3rd edition, informa
healthcare, New York.
5. Box GEP, Hunter WG, Hunter JS. Statistics for Experimenters. John Wiley, 1978.
6. Hillenbrand JM, Gayvert RT. Open Source Software for Experiment Design and Control.
Journal of Speech, Language, and Hearing Research, 2005; 48: 45–60.
7. Li He. Design of Experiments Software. The Chemical Information Network, 2003.
8. Anderson MJ, Whitcomb PJ. DOE Simplified: Practical Tools for Effective
Experimentation, 2nd Edition, 2007
9. Anderson MJ, Whitcomb PJ. DOE Simplified: Practical Tools for Effective
Experimentation, 2nd Edition, 2000
10. Anderson MJ, Whitcomb PJ. RSM Simplified: Optimizing Processes Using Response
Surface Methods for Design of Experiments, Productivity Press, 2004
11. Stat-Ease Available from: http://www.statease.com/software.html
12. Mendyk A, Jachowicz R, Fijorek K, Dorożyński P, Kulinowski P, Sebastian P. KinetDS:
An Open Source Software for Dissolution Test Data Analysis, Dissolution Technologies,
Dissolution Technologies, 2012; 1-11.

www.wjpps.com Vol 4, Issue 1, 2015. 492

Virag et al. World Journal of Pharmacy and Pharmaceutical Sciences

13. IDIS, Tablet dissolution testing data management software. Open architecture 21 CFR
Part11, ICALIS data system limited. Available from: http://www.icalis-
us.com/IDIS_pdf.pdf.
14. Seenivasagam R, Hemavathi K, Sivakumar G, Niranjan V. Discovering novel carriers for
oral insulin tablets: a pharmacoinformatics approach. International Journal of
Bioinformatics Research and Applications, 2013; 9(2): 184-206.
15. Mallick M, Odedra D, Vidyarthi AS, Shankaracharya. Meropenem: a potent drug against
superbug as unveiled through bioinformatics approaches, International Journal of
Bioinformatics Research and Applications, 2013; 9(2): 109-120.
16. Udayakumar M, Hemavathi K, Shanmugapriya P, Seenivasagam R. Receptor-Based
Pharmacophore Tool for Design and Development of Next-Generation Drugs,
International Journal of Bioinformatics Research and Applications, 2013; 9(5): 487-516.
17. Wei Hu. Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy in
Breast Cancer Using Sparse Logistic Regression, International Journal of Bioinformatics
Research and Applications, 2013; 9(3): 242-260.

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