Research & Reviews: A Journal of Drug Formulation, Development and Production (RRJoDFDP) is a Journal focused towards the publication of current Research/Review work carried out in area of Drug Formulation, development and production. Focus and Scope Covers Drug Development Novel drug delivery systems International Drug regulatory Affair Pharmacodynamics & pharmacokinetics Medicinal Chemistry Topical Formulations Galenic formulations Injectable formulations Sub-micron and Nano-emulsions

1. ISSN 2394-1944 (Online)
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eknologi MARA, Puncak Alam, Selangor,
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ChemistryAnalysis & QA
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of Pharmacy , A.P., India.
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Research Center Theagenion Cancer
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Pharmacy College (SDPC), Surat,
Gujarat, India.
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Professor, Department of Pharmaceutics,
Manipal College of Pharmaceutical Sciences,
Manipal University,India.

8. Editorial Board
Dr. Mahalaxmi Rathnanand
Associate Professor ,Dept of
Pharmaceutics Manipal College of
Pharmaceutical
Sciences, Manipal, India.
Dr. Mohamed Salama
Professor,Faculty of Pharmacy,
UiTM , Malaysia.
Dr. Poonam Singh
Scientist CSIR-Central Drug Research
Institute, Lucknow.
Dr. Pranav Shah
Associate Professor, Maliba Pharmacy College,
Maliba Campus, Surat, Gujarat, India.
Dr. Neeraj Kumar Fuloria
Faculty of Pharmacy, AIMST University,
Malysia, Malaysia.
Dr. Mohd Shihabuddin B. A. Noorden
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Dr. Rabi Bhatta
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Research Institute, Lucknow, India.
Dr. Rama Pati Tripathi
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CSIR-Central Drug Rsearch Institute
Medicinal and process chemistry Division
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Dr. S. K. M. Habeeb
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Bioinformatics,
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Campus, SRM University, India.
Dr. Sanghapal D. Sawant
CSIR-Indian Institute of Integrative
Medicine,
Jammu, India.
Prof. Dr. Sapna Shrikumar
Principal, Moulana College of Pharmacy,
Angadippuram (P.O),
Perinthalmanna, Malappuram, Kerala,
India.

9. Editorial Board
Dr. Shashank K Singh
Senior Scientist,CSIR-Indian institute of
Integrative Medicine ,Canal Road
Jammu, India.
Mr. Soh Yee Chang
Faculty of Pharmacy
UiTM Puncak Alam Campus
Malaysia.
Dr. V. Ravichandran
Faculty of Pharmacy,AIMST University,
Semeling - 08100,Kedah, Malaysia.
Mr. Viral Dineshchandra Jagiwala
Assistant Professor, Shree Dhanvantary
Pharmacy College, Surat, Gujarat, India.
Dr. Suneel .I.Majagi
Associate Professor Department of
Pharmacology J.N.Medical College
Belgaum-590010.
Karnataka.
Dr. Sridevi Chigurupati
Senior Lecturer Faculty of Pharmacy,
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Dr. Vivek Bhosale
Scientist, Division of Clinical and
Experimental Medicine CSIR-Central
Drug Research Institute, Lucknow, India.
Dr. Waseem Rizvi
Associate Professor
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College, A. M. U, Aligarh, India.
Dr. Santanu Chakraborty
Assistant Professor, Department:
Pharmaceutics, Dr. B. C. Roy Engineering
College, Kolkata, India.
Dr. Yahaya Bin Hassan
Head, Faculty of Pharmacy, Universiti
Teknologi MARA(UiTM) , Selangor ,
Malaysia.
Dr. Sandip Prabhakar Zine
Assistant Professor, Department of
Pharmaceutical Chemistry,
Vivekanand Education Society's College of
Pharmacy, Mumbai, India.
Mr. Parmeshwar Bajirao Katare
M.S (Pharm) Pharmacology and Toxicology,
Drug Discovery Research Center (DDRC),
(THSTI), Udyog Vihar, Gurgaon, Haryana,
India.

10. Editorial Board
Dr. Nahlah Elkudsiah Ismail
Faculty of Pharmacy, Universiti Teknologi
MARA (UiTM) Puncak Alam Campus,
Bandar Puncak Alam, Selangor, Malaysia.
Dr. Mudit Dixit
Head-Department of Drug Regulatory Affairs
& Assistant Professor (Pharmaceutics)
(Senior Grade), NGSM Institute of
Pharmaceutical Sciences, Mangalore, India.
Dr. P.K. Kulkarni
Professor and Head, Dept of Pharmaceutics,
J.S.S.College of
Pharmacy, S.S.Nagar, Mysore, Karnataka,
India.
Dr. R Narayana Charyulu
Vice Principal, Professor & HoD Department
of Pharmaceutics, Nitte Gulabi Shetty
Memorial Institute of Pharmaceutical
Sciences, Deralakatte, Mangalore – 575 018
Dr. Sangamesh B. Puranik
Director, Drishti Institute of
Distance Learning,
Bangalore, India

11. It is my privilege to present the print version of the [Volume 3 Issue 3] of our Research & Reviews:A
Journal of Drug Formulation, Development and Production, 2016. The intension of RRJoDFDPis to
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Ihopeyouwillenjoyreadingthisissue andwewelcomeyourfeedbackonanyaspectof theJournal.
Dr.ArchanaMehrotra
ManagingDirector
STM Journals
Director's Desk
STM JOURNALS

12. 1. Electronic Common Technical Document (eCTD): A Review of History, Benefits of Implementing,
Challenges, Modules and Risks Involved in eCTD Publishing
Praveen Agarwal, Anil Dewangan, Pavani Duggi 1
2. Spectrofluorimetric Method for the Estimation of Avanafil in Bulk and their Tablet Dosage Form
Pratik M. Tailor, Vrutika V. Patel, Ashish D. Mishra, Shailesh A. Shah, Dinesh R. Shah 17
3. A Brief Note on Different Concept of Biowaiver
Mudit Dixit, Rohit Dixit, Vasanth Samaga, Ganapayya Bairy, Ajay Bairy 22
4. In Vitro–In Vivo Correlation (IVIVC): A Strategic Tool in Drug Product Development
Vivek P. Chavda, Dhaval Shah, Hemal Tandel, Moinuddin Soniwala 31
5. Hepatic Disorders: Ayurvedic Perspective
Nishant Shukla 55
ContentsResearch & Reviews: A Journal of Drug Formulation, Development and Production

13. RRJoDFDP (2016) 1-16 © STM Journals 2016. All Rights Reserved Page 1
Research & Reviews: A Journal of Drug Formulation, Development and Production
ISSN: 2394-1944(online)
Volume 3, Issue 3
www.stmjournals.com
Electronic Common Technical Document (eCTD): A
Review of History, Benefits of Implementing, Challenges,
Modules and Risks Involved in eCTD Publishing
Praveen Agarwal*, Anil Dewangan, Pavani Duggi
PAREXEL International Pvt. Ltd., Bangalore, Karnataka, India
Abstract
Electronic Common Technical Document (eCTD) is a topic of increasing interest in the
pharmaceutical environment. eCTD is an interface for the pharmaceutical industry to agency
transfer of regulatory information. Since June 2003, applicants have had the option of
submitting an eCTD in parallel with the paper submission (Common Technical Document),
following sign-off by the International Conference on Harmonization Steering Committee of
the eCTD Specification document at Step 4. It is designed to make regulatory submissions
easier and more efficient for drug makers and for regulators. When it comes to eCTD
submission, there continues to be differences among different countries and even ICH regions.
The standardization that electronic submissions will bring will allow for much greater
consistency not only for the regulators but also for organizations. It is important that eCTD
ready documents are prepared by authoring them in eCTD compliant templates. If this is not
undertaken, a large amount of the “publishing time” is spent in document reformatting. As the
move from paper-based to eCTD submissions continues around the world, a multitude of
challenges is to be faced regulatory departments. This paper describes eCTD History,
Benefits of Implementing, Challenges, Modules, Risks involved in eCTD publishing and
Quality Control.
Keywords: Electronic Common Technical Document, Benefits, Challenges, Modules
INTRODUCTION
After decades of using paper, the goal is the
electronic transfer of drug applications and
their review across submission formats,
procedures, and regions came in. Electronic
Common Technical Document (eCTD) is a
topic of increasing interest in the
pharmaceutical environment. The eCTD is the
electronic equivalent to the Common
Technical Document (CTD) format. The
eCTD is defined as an interface for industry to
agency transfer of regulatory information
while at the same time taking into
consideration the facilitation of the creation,
review, lifecycle management and archival of
the electronic submission. The eCTD
specification lists the criteria that will make an
electronic submission technically valid. The
focus of the specification is to provide the
ability to transfer the registration application
electronically from industry to a regulatory
authority. It was developed by the
International Conference on Harmonization
(ICH) Multidisciplinary Group 2 Expert
Working Group (ICH M2 EWG). In
November 2003, the ICH M2 group revised
the specification for the eCTD to version 3.2,
which remains the current version. ICH eCTD
is an internationally driven standard designed
to reduce cost in the administration,
assessment and archiving of applications for
marketing authorization of medicinal product
for human use, to reduce the use of paper and
streamline the assessment process making the
system more efficient. It provides a common
global standard for companies to electronically
submit the quality, safety and efficacy
information required for approval of a new
drug to regulatory agencies in the United
States (US), European Union (EU), Canada
and Japan etc. that imposes minimal restriction
to the industry and agencies [1, 2]. The
primary technical components are:
 A high-level folder structure (required).
 An Extensible Markup Language (XML)
“backbone" files which provides metadata

14. RRJoDFDP (2016) 17-21 © STM Journals 2016. All Rights Reserved Page 17
Research & Reviews: A Journal of Drug Formulation, Development and Production
ISSN: 2394-1944(online)
Volume 3, Issue 3
www.stmjournals.com
Spectrofluorimetric Method for the Estimation of Avanafil
in Bulk and their Tablet Dosage Form
Pratik M. Tailor*, Vrutika V. Patel, Ashish D. Mishra, Shailesh A. Shah, Dinesh R. Shah
Department of Quality Assurance, Maliba Pharmacy College, Tarsadi, Gujarat, India
Abstract
A simple and sensitive spectrofluorimetric method has been developed for estimation of
Avanafil in bulk and in their tablet dosage form. Avanafil in methanol produces fluorescence
at 367 nm (λem) with excitation at 314 nm (λex). Linearity range was found to be 200–1000
ng/ml with correlation co-efficient 0.999. The limit of detection (LOD) and limit of
quantitation (LOQ) for the developed method were found to be 7.32 and 22.18 ng/ml,
respectively. The developed method was found to be specific, sensitive, accurate and precise.
It was successfully used for estimation of Avanafil in its tablet dosage form. The content of
Avanafil in two marketed formulations was found to be 96.91 and 97.95% of label claim.
Keywords: Avanafil, spectrofluorimetric method, excitation, emission
INTRODUCTION
Avanafil chemically, 4-{[(3-chloro-4
methoxyphenyl) methyl] amino} -2-[(2S)-2-
(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin
-2-ylmethyl)pyrimidine-5-carboxamide is a
PDE5 Inhibitors, used in treatment of erectile
dysfunction (Figure 1) [1]. Avanafil is not
official in Indian Pharmacopoeia, British
Pharmacopoeia, European Pharmacopoeia and
United State Pharmacopoeia. Literature survey
reveals that Colorimetric and HPLC methods
have been reported for Avanafil. Spectro-
photometry and HPTLC methods have been
reported for combined dosage form [2–8]. This
study presents a new spectrofluorimetric
method for the determination of Avanafil in
bulk and their tablet dosage form.
Fig. 1: Chemical Structure of Avanafil.
EXPERIMENTAL
Apparatus
Spectrofluorophotometer (Shimadzu, RF-
5301) with single 1 cm quartz cell with RFPC
software was utilized in the study.
Reagents and Materials
Avanafil was kindly supplied as a gift sample
by Sunrise Remedies, Pvt. Ltd, Ahmedabad,
Gujarat, India. Methanol AR grade (s d fiNE-
CHEM ltd.) was utilized in the study.
AVANA-50 and AVANA-100 tablets were
gifted by Sunrise Remedies, Pvt. Ltd,
Ahmedabad, Gujarat, India.
Preparation of Standard Stock Solution of
Avanafil
Accurately weighed 10 mg of Avanafil was
transferred to 10 ml volumetric flask,
dissolved and diluted up to mark with
methanol to obtain a solution having strength
of 1000 µg/ml.
Spectrofluorimetric Conditions
Spectrum Type: Excitation and Emission
Scan range: 220–900 nm
Recording range: 0.000–1000.00
Scanning speed: Super
Slit width (nm): EX:5; EM:5
Response time (sec): Auto

15. RRJoDFDP (2016) 22-30 © STM Journals 2016. All Rights Reserved Page 22
Research & Reviews: A Journal of Drug Formulation, Development and Production
ISSN: 2394-1944(online)
Volume 3, Issue 3
www.stmjournals.com
A Brief Note on Different Concept of Biowaiver
Mudit Dixit*, Rohit Dixit, Vasanth Samaga, Ganapayya Bairy, Ajay Bairy
Beloorbayir Biotech Ltd., K.R. Road, Banashankari, Bangalore, Karnataka, India
Abstract
The aim of the present work was to understand the concept of to waive a complete and
systemic bioequivalence (BE) study. Biowaiver or request for a biowaiver is a fast track
approach to boost the drug development process. Over the past three-four years, the
biowaiver market has shown greater number of biowaiver submissions and the wider use of
in-vitro permeability study. Biowaiver is a beneficial approach for getting approval of
abbreviated new drug application (ANDA). While BCS based biowaiver is the novel approach
to gain approval for new drug application (NDA), investigate new drug application (IND) as
well as ANDA. A biopharmaceutics classification system (BCS) based biowaiver is an
exemption from conducting human bioequivalence studies when active ingredient and dosage
form meet criteria of solubility, permeability and dissolution. The current work focuses on
different types of biowaiver approaches and the criteria for the applicability of BCS based
biowaivers in different geographic scopes with regard to global development strategy. There
is a comparison of global guidelines on provisions availability for different types of biowaiver
approaches as well as for requirements of biowaiver based on BCS. From comparison of
different global guidelines it is reviewed that most of the guidance resembles to the USFDA,
EU and WHO guidelines because most of the regulatory authorities are following the BCS
based biowaiver concept as one of the three main guidance documents (USFDA, EMA, JP,
WHO) or a combination of specific requirements.
Keywords: Bioequivalence, biowaiver, ANDA, NDA, INDA, BCS based biowaiver
INTRODUCTION
As per survey of FDA, every year only 18 to
26 new chemical entities (NCEs) get approved
as a new drug application (NDA). Whereas,
pharmaceutical companies file thousands of
abbreviated new drug applications (ANDAs)
to get an approval as a generic version of
innovators every year. To get an approval for
ANDAs, generic formulation should be proven
bioequivalent to that of reference listed drug
(RLD).
For market authorization of generics, instead
of non-clinical and clinical studies, only
bioequivalence (BE) study is required. At drug
development stage, only one formulation
becomes eligible for marketing from many of
formulations. In that case, biowaiver concept
comes into picture to reduce unnecessary time
and expense of BE study for each formulation.
Biowaiver is a kind of ANDA filing, which
applies to reduce time and cost from a
complete, systemic BE study.
BIOWAIVER
Simply, biowaiver is considered as waiver of
clinical bioequivalence studies. As per WHO
guidance, “The term biowaiver is applied to a
regulatory drug approval process when the
dossier (application) is approved based on
evidence of equivalence other than in-vivo
bioequivalence test” [1].
Different Approaches for Biowaiver
Different drug regulatory authorities approve
biowaiver for different conditions, which are
summarized in Figure 1 and described below
in brief.
Biowaiver for Specific Dosage Forms
Due to certain characteristics of some specific
formulations, BE study may not be required.
In that case, bioequivalence between the test
and the reference product can be presumed
without any further in-vivo experiments. This
kind of biowaiver can be possible for aqueous
oral solutions, parenteral solutions and topical
solutions (e.g. eye drops). One of the major

16. RRJoDFDP (2016) 31-54 © STM Journals 2016. All Rights Reserved Page 31
Research & Reviews: A Journal of Drug Formulation, Development and Production
ISSN: 2394-1944(online)
Volume 3, Issue 3
www.stmjournals.com
In Vitro–In Vivo Correlation (IVIVC): A Strategic Tool in
Drug Product Development
Vivek P. Chavda1,
*, Dhaval Shah2
, Hemal Tandel2
, Moinuddin Soniwala1
1
Department of Pharmaceutics, B. K. Mody Government Pharmacy College, Rajkot, Gujarat, India
2
Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India
Abstract
In a recent era many concepts are dealing as an emerging tool for the drug delivery
application like Biopharmaceutical Classification System (BCS), In vitro and In vivo study,
and Bioavailability/Bioequivalence (BA/BE) study etc. To determine Therapeutic efficiency in
vitro is not enough so the concept of In vitro-In vivo correlation (IVIVC) is playing as an
convincing correlation with this for concept of pharmaceutical dosage forms have been a
main focus of attention of pharmaceutical industry, academia, and regulatory sectors.
Formulation, Development and optimization of dosage form is an integral part of research
governed by technology transfer to scale up the manufacturing and then concurrent validation
governed from the marketing of any therapeutic agent which is indeed a time consuming and
costly process. A good correlation is a tool for predicting in vivo results based on in vitro data
using IVIVC which gives indirect cost effective approach to dosage form optimization of trials
in human, fixes dissolution acceptance criteria, and can be used as a tool to substitute for
further bioequivalence studies. IVIVC can be used in the development of new pharmaceuticals
to reduce the number of human studies during the formulation development as the main
objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support
biowaivers. This review article represents the FDA guidance, development, evaluation, and
validation of an IVIVC to grant biowaivers, and to set dissolution specifications for oral
dosage forms, biopharmaceutical classification systems (BCS), BCS biowaivers, and
applications of BCS in IVIVC development and concept of mapping. The importance of
dissolution media and methodology and pharmacokinetic studies in the context of IVIVC has
been highlighted. The principles of IVIVC also merged with nonoral products such as
parenteral depot formulations and novel drug delivery systems as well.
Keywords: Fundamentals of IVIVC, Biopharmaceutical Classification System (BCS),
Objectives, Biowaiver, Levels, Correlation, Dissolution methodologies, IVIVC of Novel
Dosage Forms, Applications of IVIVC
INTRODUCTION
From biopharmaceutical point of view, in
vitro-in vivo correlation (IV-IVC) is a
predictive mathematical treatment describing
the relationship between an in vitro property of
a dosage form (usually the rate or extent of
drug release) and a relevant in vivo response,
(e.g., plasma or urine drug concentrations or
amount of drug absorbed). It is recommended
by various regulatory bodies and mostly
applicable to drug dosage forms for oral routes
and sustained release products. It is a useful
tool for drug dosage form development,
because a successful correlation can assist in
the selection of drug formulation with
appropriate and acceptable dissolution criteria,
and depending on its predictiveness, it can be
used as a forecast or surrogate for further
bioequivalence studies. There are different
categories of IVIVC; A, B, C and D. In the
rapidly emerging field of novel drug delivery
systems, the need to establish correlation
between in vitro drug release (dissolution) data
and in vivo drug profiles is ever growing. Such
correlations would not only allow more
efficient drug and product development but
also economize resources and lead to
improved product quality. The bioavailability
implications of dissolution should never be
accepted on faith; rather it has to be proved
through carefully designed in vitro-in vivo
correlation studies. Long back, Wagner had

17. RRJoDFDP (2016) 55-59 © STM Journals 2016. All Rights Reserved Page 55
Research & Reviews: A Journal of Drug Formulation, Development and Production
ISSN: 2394-1944(online)
Volume 3, Issue 3
www.stmjournals.com
Hepatic Disorders: Ayurvedic Perspective
Nishant Shukla*
Uttaranchal Ayurveda College, Dehradun, Uttaranchal, India
Abstract
Kamla is a very common disease in our country. It is difficult to diagnose. If properly
diagnosed, the Sadhya: asadhyat (prognosis or curability and incurability) can be forecasted
easily. The patient also can be informed what treatment is to be given. Varieties: Ayurvedic
classics give two types of Kamla, viz Kosthashrit and Shakhashrit (Caraka Sutra) while in
chikitsa 16 maharishi Caraka has classified the same in two different names: (1) Koshtha:
Shakhasrit and (2) Shakhashrit Kamla are given. Kamla can occur as a result of faulty
treatment also; in other words Kamla can also be produced as an iatrogenic disorder also.
Keywords: Kamla, Kosthashrit, Sadhya: asadhyat
INTRODUCTION
In the modern science, some of the drugs are
considered as hepatotoxic drugs. In Ayurved
no such drugs like hepatotoxic drug is
mentioned but faulty treatment can produce
Kamla, i.e., that line of treatment can be
considered as hepatotoxic treatment. The
author of this paper has come across and
treated a Kamla patient, which was produced
as a result of surgical treatment in bleeding
piles. Thus the diagnosis and treatment
becomes easy if proper history is available
from the patient. The physician also should
note the history properly.
Main dosha involved is pitta. Either the
formation rakta is not proper, i.e., raktaposhaka
sara or the pitta is obstructed somewhere in the
passage. Cakrapani has mentioned two types of
pitta—one is ranjak, i.e., pitta which is
necessary for colouring rasa and formation of
blood. Other variety is called mala ranjaka
pitta, i.e., which gives colour to the fecal
matter. It is necessary here to explain briefly the
formation of malaranjak pitta, i.e., bile.
Both Ayurved and modern science say that
pitta is produced from rakta. rakta—anu
(R.B.C.), when dead, break into two types of
coloured agents or chemicals. They are
bilirubin and biliverdin. The colour of
bilirubin is yellow while that of biliverdin is
green. When both are mixed the colour
becomes greenish yellow. This goes to yakrit,
i.e., liver. The coloured agent gives colour to
the bile. Bile is collected in gall bladder. When
necessary it comes to the intestines through
common bile duct. This is the physiology of
bile. Bile plays a very great role in digestion of
fat ingested. The pancreatic juice, the secretion
from the submucous glands of the small
intestines and bile, digests the food ingested.
Any defect at any level will produce
Ajeerna—indigestion or dyspepsia. Bile plays
a role in digestion of fat. So if bile is not
properly formed, the digestion of fat will be
improper.
Schematically, the formation of bile is as
under the Figure 1.
Any pathology, whether Doshic or Dhatujanya
or organic lesion will lead to jaundice. For
example, excessive break down of R.B.C. will
lead to excessive bile salt and pigments. Some
of the bile pigments or salts will be utilized for
the formation of bile; but the remaining
pigments or salts will circulate in whole body,
which will produce greenish yellow pigments
in the body specially conjunctiva, nails, and
skin. Moreover, the urine and stool will also
be yellow.

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