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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 RRJoDFDP is to create an atmosphere that stimulates vision, research and growth in the area of Drug Formulation, Development and Production. Timely publication, honest communication, comprehensive editing and trust with authors and readers have been the hallmark of our journals. STM Journals provide a platform for scholarly research articles to be published in journals of international standards. STM journals strive to publish quality paper in record time, making it a leader in service and business offerings. The aim and scope of STM Journals is to provide an academic medium and an important reference for the advancement and dissemination of research results that support high level learning, teaching and research in all the Science, Technology and Medical domains. Finally, I express my sincere gratitude to our Editorial/ Reviewer board, Authors and publication team for their continued support and invaluable contributions and suggestions in the form of authoring writeups/reviewing and providing constructive comments for the advancement of the journals. With regards to their due continuous support and co-operation, we have been able to publish quality Research/Reviews findings for our customers base. I hope you will enjoy reading this issue and we welcome your feedback on any aspect of the Journal.
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Research & Reviews: A Journal of Drug Formulation, Development and Production
Contents
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
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
RRJoDFDP (2016) 1-16 © STM Journals 2016. All Rights Reserved
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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. Spectrophotometry 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, RF5301) 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 fiNECHEM 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
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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
RRJoDFDP (2016) 22-30 © STM Journals 2016. All Rights Reserved
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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 1
Vivek P. Chavda1,*, Dhaval Shah2, Hemal Tandel2, Moinuddin Soniwala1
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
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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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