Sudalai Kumar SS

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Design, Discovery and Development of Pharmaceutical Solids

File No : ECR/2016/001638/CS (Ver-1) Submitted By : Sudalai Kumar S Submission Date : 30-Sep-2016

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Proposal

Proposal File No :

ECR/2016/001638/CS (Ver-1)

Proposal Details Project Title :

Design, Discovery and Development of Pharmaceutical Solids

Scheme :

Early Career Research Award

Broad Area :

Chemical Sciences

Sub Area :

Chemical Sciences(ECR)

Duration In Month :

36

Total Cost (in Rs.) :

50,00,000

Name of Principal Investigator :

Sudalai Kumar S

Email ID :

[email protected]

Date of Birth :

13-May-1987

Contact No :

+919952885464

Category :

OBC

Gender :

Male

Nationality :

Indian

Is differently abled : No

Designation :

ASSISTANT PROFESSOR

Department :

PI Address :

11a,Jawaharlal street, tirunelveli town, tirunelveli

PI Institute :

Francis Xavier Engineering College

PI Institute Address : 103/g2, bypass road, vannarpet, tirunelveli, Tirunelveli, Tamil nadu627003 Institute Joining Date :

SCIENCE AND HUMANITIES

State :

Tamil nadu

Pin Code :

627006

01 June, 2015

CO PI Details : Name & Designation Date of Birth

Mobile No.

Email

Kannan Masanam 15-Oct-1986 (Assistant Professor)

917305394741

mkan1986serb@gmail Thiruvalluvar College, .com Ambasamudram-PapanasamUpper Dam Road, Tirunelveli, TAMIL NADU-627001

Project Summary :

Institute Details

This proposal would describe the novel progress of researches in the single components (pure APIs), multi-components (cocrystals/salts) including eutectics in understanding the structure property relationship using X-ray diffraction techniques, spectroscopy techniques FT-IR, Raman, ss-NMR and would also open up the possibilities in the development of desirable polymorph or cocrystals/salts based on pharmaceutical importance of amphoteric drugs. Totally 20 drugs were selected from this category and utilized for solid form screening. The combination of design, discovery and development of these drugs followed by characterization of these drug products would be utilized for the new drug products and formulation methods. As these amphoteric compounds, are more prone to different solid forms and therefore these pure drugs are considered for the above studies using different crystallization conditions due to their excellent thermodynamic

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stability, solubility, dissolution rate and bioavailability as well as high chemical and thermal stability with polymorphs or salts or cocrystals. This design and synthesis of drug products lead to modify the characteristics of the potential drug substance and permit the development of dosage forms with good solubility, bioavailability, stability, manufacturability, and patient compliance of different drugs. Hence it is utilized for several applications in low aqueous soluble drugs as many as (80%) drug candidates in the pipeline (NCEs) will pose a solubility problem. Polymorphism in pharmaceutical solids (APIs, cocrystals, salts and solvates) has attracted much attention due to their excellent thermodynamic stability, solubility, dissolution rate and bioavailability as well as high chemical and thermal stability. Therefore, the crystallization of pharmaceutical crystalline materials through epitaxial growth, solution mediated and high temperature crystallization condition with full control over the phase transition is becoming a challenging project and thus it would attract the many pharmaceutical scientists to work on several drugs in future. Objective :

• To design and synthesis the drug products lead to modify the characteristics of the potential drug candidates. To develop the solid dosage forms with good solubility, bioavailability, stability, manufacturability and patient compliance of amphoteric drugs. • To study drug materials and its characterization would help us to understand the structure property relationship and used in low aqueous soluble drugs as many as (80%) drug candidates in the pipeline. •To open wide scope in supramolecular and crystal engineering approaches in pharmaceutical applications.

Keywords :

drug polymorph, pharmaceutical cocrystal and salt, phase transition, X-ray diffraction, solubility and dissolution.

Expected Output Structural modifications in drug materials using this 3D approach called Design, Discovery and and Outcome of the Development of drug products lead to give different solid dosage forms and these applications will proposal : be directly used in R and Ds in India. The crystal engineering (cocrystal and salts) strategies are always a novel approach in the design and development of drug products in the pharmaceutical field and would attract many publications and patents. The new drug products will also follow the FDA procedures to become a modified drug immediately after addressing the solubility and stability issues in amphoteric drugs. Clinical trials will be performed at the end of this project and other formulation requirements will be focused to become a new drug product. Academically it is important to know if there will be a new synthon, tautomer, conformer and packing pattern in the screening of new solid forms.

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DST SERB Early Career Research Award

Design, Discovery and Development of Pharmaceutical Solids 1. Origin of the Proposal Pharmaceutical solid form (polymorphic APIs, cocrystals, salts and solvates) search in solid drug compunds has been attracted much attention and interest due to their excellent thermodynamic stability, solubility, dissolution rate and bioavailability as well as high chemical and thermal stability [1]. The phase change of solid form materials at different pressure and temperature is of fundamental interest in solid-state chemistry and physics [2]. Therefore, the crystallization of pharmaceutical crystalline materials through epitaxial growth, solution mediated and high temperature crystallization condition with full control over the phase transition become one of the most exciting areas of polymorph research in pharmaceutical science [3]. So the assessment of the role of hydrogen bonds and weak interactions in determining the crystal structure and number of possible polymorphs and cocrystals can be confirmed by single crystal and powder X-ray diffraction methods [4]. The thermodynamic and kinetic relationship between the polymorphs can be established by thermal analysis and slurry methods [5]. These studies are useful to understand the interplay between the solid forms and the pharmaceutical requirements in determining the overall stability and phase transition of drug products. In this way, it is aimed to describe the novel progress of researches in the single components (pure APIs), multi-components (cocrystals/salts) including eutectics in understanding the structure property relationship using spectroscopy techniques FT-IR, Raman, ss-NMR and also would open up the possibilities in the developments of desirable polymorph based on pharmaceutical importance [6].

2. Review of Status of Research and Development in the Subject 2.1. International Status Solid form synthesis is a new and broad area that includes polymorphs, cocrystal, salt, eutectics, solid solution, solvates and amorphous phases and it covers the various research topics of physical, organic, inorganic, metal-organic, supramolecular, computational, pharmaceutical and solid materials in terms of synthesis and characterization [7-8]. McCrone defined the term polymorph as a solid crystalline phase of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid state [9]. It is the usual occurrence in which same chemical substance exhibits different 1

S. Sudalai Kumar, FXEC.


crystalline arrangements in the crystal lattice for any solid materials [10]. Polymorphism in organic compounds is very often and of course fundamental importance since its ability to change the drug properties such as solubility, dissolution, toxicity and bioavailability for different crystal forms (Ritonavir: solubility order I > II and Mebendazole: order of toxicity effect B > A

C) [11-12]. As a result, polymorphism can affect the quality, safety, and

efficacy of a drug product. These polymorphs are classified into three different types mainly conformational, packing and synthon polymorphs based on the differences in conformational polymorphs (Tolbutamide drug pentamorphs) [13], crystal packing polymorphs (2-(pTolylamino)nicotinic acid trimorphs) [14] and synthon polymorphs (Furosemide drug trimorphs) [15] in the crystal structures. Some other differences are also occurring in the solid state of crystalline materials, they are intramolecular proton transfer (Zwitterionic and Neutral polymorphs: Norfloxacin drug trimorphs) [16] and tautomeric transfer of atoms (Tautomeric polymorphs: for 2-Thiobarbituric acid tetramorphs) [17]. Significantly, the zwitterionic polymorphs exhibit high solubility and stability over the neutral polymorphs for some of the amphoteric drugs (Clonixin drug tetramorphs) [18]. Recently, Matzger reported the nonamorphic Flufenamic acid drug [19] as the drug having maximum number of polymorphs for a molecule in the CSD data till date.

The next example is ROY

polymorphism with different colours in solid forms [20]. Finding a new solid form suffers sometimes from a ‘disappearing polymorph’, which can be found to our surprise that a second polymorph of maleic acid was obtained 124 years after evidence of the first crystal form was reported [21]. Nowadays polymorphs are common in multi-components called cocrystals and salts also and they obviously affect the solubility and stability of the drugs. Trask et al reported that two polymorphs of the cocrystal of caffeine with glutaric acid showed differences in stability property under elevated relative humidity (RH) conditions [22]. Six structures of new salt forms of Carbamzepine (CBZ) and Cytosine (CYT) are reported and their occurrence and structural similarities discussed by [23]. The modern techniques and the methods that generally used to obtain the new polymorphs are control of supersaturation level, control of nucleation temperature, solvent screening [24], Heating and sublimation of the materials [25], low temperature and high temperature evaporation [26], roto vapor fast evaporation [27], seeding technology [28], capillary crystallization [29], introduction of additives [30], polymer-induced heteronucleation [31], nucleation confined in nanopores [32], heteronucleation on substrates such as ionic liquids and gels [33-35], laser2



induced nucleation [36], self-assembled monolayers and Langmuir films [37-38] and crystal structure prediction [39-40] . There are many characterization techniques to identify these polymorphs mainly single crystal X-ray and powder XRD techniques used widely. Theramal analysis is carriedout by Differential Scanning Calorimetry (DSC), Hot Stage Microscopy (HSM) and Variable temeprature PXRD. The spectroscopy techniques FT-IR, Raman and solid state NMR are the supporting techniques to confirm the new phase formation. The geometrical, conformational, hydrogen bonds and spectroscopic features are compared among identified polymorphic forms in order to point out some important differences between them, which could give in-depth information of the structure–property relationships. CSD [41] data revealed that 1157 (89.2%) have two polymorphs, 114 (8.8%) have three polymorphs, and only 26 (1.4%) molecules have four polymorphs. Six molecules are there in the pentamorphic systems where as only one molecule has hexamorphs and heptamorphs. Polymorphism in 114 cocrystals are reported [42]. Therefore, we believe that our research ideas on crystallizing the drug materials not only could stimulate development on the new crystalline materials but also would open up possibilities in the development of multicomponents. The use of coformers for solid form screening is to lift up the skills in the proper analysis of crystal phases and the study of structure property relationship. 2.2 National Status: Indian Institute of Science, National Chemical Laboratory, University of Hyderabad, IISERs, CSIR institutes, BARC, IITs, Indian Association for the Cultivation of Science, Institute of Minerals and Materials Technology and National Materials Research Laboratory the active participants in the field for the development of drug and material properties. Desiraju et al in IISc is carrying out many academic and application research projects in the design of new drug modifications using different crystal engineering techniques, i.e., Nanoindentation [43]. Nangia et al in UoH/NCL is focussing on low aqueous soluble drugs with aim of chalk to salt method in developing drug properties [44]. Choudhury and Reddy et al in IISER is solving the drug issues using cocrytsal approach and bending behaviour of some crystals using crystal-property relationship studies respectively [45]. Some other independent research groups in NIPER institutes are also working on these low aqueous and unstable drugs using size reduction and synthesis of amorphous phases [46]. All these works were carried out independently by different groups on different solids and compared their impact on solubility and stability. 3



2.3 Importance of the proposed project in the context of current status: Structure-property relationship is a powerful concept not only in chemistry but also in solid-state material science, environmental science, biology, biochemistry, polymer science, medicine, engineering, and nutrition fields [47]. The changes in properties of many materials result primarily from the modifying the structural arrangements of molecules/atoms/ions in the crystal lattice. Some of the examples are polymorphs, cocrystals, salts, solvates, amorphous phases and eutectics reported for modifying the drug properties without any more chemical modifications [48]. Heterogeneous nucleation of self-assembled monolayers and Langmuir films represent valuable alternative methods to control the crystal growth processes with a possible control over the polymorphic transition of the produced crystalline polymorphs [49]. These techniques are also really helpful in many cases where the desirable crystals could not be crystallized by normal solvent evaporation and traditional crystallization methods. There are some families of related molecules, such as the sulphonamides, ROY derivatives, barbiturates, carbamazepine derivatives, and fenamates, which appeared to have a strong tendency for polymorphism [50]. These crystal structures can be taken into the account of correalting the struture-property relationships such as solubility, dissolution, stability, compactibility and luminiscent behaviour [51]. All these polymorphores can be subjected into the reproduction of reported polymorphs using the different crystallization conditions. The new polymorphs also can be discovered by our templates and could be checked for suitable drug formulations in the the coarse of structure-solubility-stability relationship studies. We assume that that the presence of transition metal ions in the liquid phase, beneath the Langmuir monolayers, will cause the formation of two-dimensional crystalline arrays that can be transferred on a solid substrate and will induce the new solid phases [52]. 2.4. If the project is location specific, basis for selection of location: Yes. Some of the crystals are reproducible only in Tirunelveli district as the ambient conditions were suitable for the crystallization of ampholitic drugs Clonixin and 2-(pTolylamino)nicotinic acid (TNA) molecules. These compounds had reproducibility issues in Hyderabad and other locations in India. As these crystallizations are giving different results in different places called Chennai, Hyderabad and Papanasam the crystallization may be

4



location specific or the environmental specific. The pressure and temperature factors are also playing vital role in location specific crystallization methods.

3. Work Plan 3.1 Methodology Crystal engineering [2a], “the understanding of intermolecular interactions in the context of crystal packing and in the utilisation of such understanding in the design of new solids with desired physical and chemical properties.” Crystal engineering strategies for design, discovery and develpment of pharmaceutical drugs via polymorphs/ cocrystals/eutectics/salts hunting have been established well in world wide for several drugs, however, the physicochemical and pharmacokinetic properties of amphoteric drug compounds (API) are the rare one in literature and it can be done by screening of

different solid forms;

polymorphs, cocrystals, eutectics and salts [7]. Therefore, it is crucial to search the solid forms of drugs with desired properties including better solubility, stability, bioavailability, and manufacturability. To discover any solid form of this drug with optimal properties require comprehensive knowledge about intermolecular interactions and the packing modes of the structure. This will greatly enhance our understanding of the structure–property relationships and the clear picture of identifying new solid form of drugs. The potential of solid form identification for enhancing the solid-state properties of drugs can be monitored by solution crystallization, solid and liquid assisted grinding, slow and fast evaporation techniques etc., [54] Generally, the solid form screening and cocrystallization is mainly used for solubility and dissolution rate enhancement [55], sensitivity enhancement of explosives [56], enantiomeric resolution, and organocatalysis by grinding of two individual components together in mortar with pestle. The traditional solid forms are polymorphs, salts and amorphous phases identified well before the last two decades but current focus will also be on other solid forms called cocrystals, eutectics and solid solution for the development of drug properties [57]. To explore this research area further, some of the drugs are selected from ampholytes which are not explored well in scientific research of design, discovery and development of solid drug products. These drugs are very important in academic and industrial interests as these structures are existing in variable solid forms such as neutral and zwitterionic. The goal of these investigations is to explore the structural properties of amphoteric drugs including 5



solubilization, tautomerism, various ionization states in single and multi component drug products. Most of the amphoteric drugs are classified as Biopharmaceutical Classification Systems (BCS) class II drugs having lowest solubility and high permeability and also have other stability issues such as hydration and polymorphic transformation (Norfloxacin and Ciprofloxacin) [58]. These issues are the special one to focus and resolve these problems in developmental stages itself. In this direction, more than 40 drugs are available as amphoteric drugs in the market having solubility, stability and hydration issues [59]. We have taken only 20 drugs for this project (in Table 1) and will take the opportunity to include all other drugs for the extensive work in future projects and address all the key issues associated with these drugs. Table 1 List of amphoteric drugs selected for our studies. S. No

Amphoteric/zwitterionic drugs

1

Meloxicam

2

Isoxicam

3

Amdinocillin

4

Benazepril

5

Ceftazidime

6

Cerivastatin

7

Cetirizine

8

Chlortetracycline

9

Daunorubicin

10

Demeclocycline

11

Doxycycline

12

Famotidine

13

Fexofenadine

14

Levocarnitine

15

Lisinopril

16

Melphalan

17

Minocycline

18

Tetracycline

19

Flunixin 6



20

Tianeptine

Clonixin, Torsemide, Tianeptine and Norfloxacin drugs from this category are the suitable examples of well studied systems and the starting targets for this project to develop their drug properties by polymorphism, cocrystallization, salt formation and eutectics composition using neat and liquid assisted grinding as well solution crystallization methods are mentioned in table 1. The solution crystallization techniques are the solvent evaporation under room temperature conditions, seeding, fast and slow evaporation techniques [60]. Mortar and pestle will be used for grinding one or more materials to produce polymorph, cocrystal, salt and eutectics. Here, alcoholic solvents, keto solvents, aromatic solvents, halogen solvents, acetonitrile and nitromethane will be used for solution crystallizations [70]. The characterization techniques are single crystal and powder X-ray diffraction methods for the identification of polymorphs and cocrystals. The solid state NMR, FT-IR and FT-Raman spectroscopy techniques are used for the identification of multi components formation in the solid state [61]. Differential Scanning Calorimetric method will be used for the establishing the thermal relationship between the solid forms. Solubility and dissolution experiments will also be performed on all identified solid forms in this work with the help of UV/Vis spectrophotometer and dissolution tester [62]. Summary of all possible solid forms and its characterization techniques are given below for amphoteric drugs in Table 2. Table 2 Analytical techniques and the observation for solid state forms Category

Techniques

Solid forms

Single crystal X-ray diffractions

Polymorphs, cocrystals, solvates and solid solution

Powder X-ray diffractions

Polymorphs, cocrystals, amorphous phase and solvates

FT-Raman and Infrared spectroscopy

Polymorphs, cocrystals, amorphous phase and solvates

X-ray diffractions

Vibrational spectroscopy

7

Information

Structure, crystallinity, chemical and phase composition, molecular weight, etc.

Structure, molecular conformation, chemical and phase composition, hydrogen bonding, etc.



Microscopy

Polymorphs, cocrystal, amorphous phase and solvates

Optical, Scanning electron and Atomic force microscopy

Surface properties, interactions between particles, etc. Polymorphs

Melting point, transitions, etc.

Thermogravimetric analysis

Solvates

Melting point, transitions, etc.

Differential scanning calorimetry

Polymorphs, cocrystals, solvates, amorphous phase and eutectic composition

Hot-stage Microscopy

Thermal methods

Thermal transitions.

Differential thermal analysis Isothermal calorimetry

NMR Spectroscopy

Crystal size and habit, etc.

Polymorphs, cocrystals, solvates and amorphous phase

Solid-state nuclear magnetic resonance spectroscopy (13C and 15 N NMR)

Melting point, transitions, heat capacity, crystallinity, etc. Heat and rate of transition, crystallinity, etc. Chemical and phase composition, structure, crystallinity, intermolecular interaction, conformational change, etc.

Unfortunately, these drugs have some reproducibility problem with solid forms in my previous work and it is therefore Self Assembly Monolayer (SAMs) and Langhumuir films (LFs) techniques can also be used for screening the solid forms. GRAS (Generally Regarded As Safe) coformers will be used for cocrystallization, salts and eutectic formation [62]. In this course of study, there may be a chance of finding robust synthon in addition to the well known supramolecular synthons i.e., acid–pyridine, phenol–pyridine, phenol–amine, acid– amide, aminopyridine–acid and amide–pyridine-N-oxide are robust heterosynthons [62]. Particularly, these drugs have reproducibility problem with the reported polymorphs and these SAMs and LFs techniques also can be used for screening the solid forms. GRAS (Generally Regarded As Safe) coformers will be used to avoid the clinical issues for cocrystallization, salts and eutectic formation. During the crystallization of new solid 8



crystalline forms, there may be chance of studying new synthon formation in addition to the well known hydrogen bonds are acid–pyridine phenol–pyridine phenol–amine acid–amide aminopyridine–acid and amide–pyridine-N-oxide are robust heterosynthons [62]. Our idea is to make APIs, cocrystals, salts and solvates and find a maximum number of possible polymorphs for those mentioned drugs by applying the SAMs and LFs induced crystallization methods and taken into the study of structure-property correlations. In this study, we will demonstrate that use of SAMs and LFs can be exploited to control the crystalline polymorphism of zwitterionic drugs and other following drugs. 3.2. Time schedule of activities giving milestones through bar diagram: This project will be continued for three years in the beginning and later will be implemented further with the funding help and permission from DST. It begins with a thorough planning, drug material preparation, screening of new solid forms such as, polymorphs, cocrystals, salts, amorphous phase and eutectics, and material characterization using FT-IR, PXRD and DSC. In the same time, the process of ordering and purchasing the equipment (DSC/UV-Vis spectrophotometer) will be initiated. After successful installation, it will be regularly utilized for characterizing the solid forms. It will be further characterized by ss-NMR and solubility measurements. Finally, we correlate the results of structure vs property; they will be presented in national as well as international conferences and published in peer reviewed journals. We will acknowledge the funding bodies DST-SERB for the financial support in all our presentations. Finally, as per usual procedures, a final report of the work done under this project will be submitted to DST SERB, New Delhi. A list of work elements are given below. No

Activities

Months (3 years) 1-3

1

4-6

7-9

1012

1315

1618

1921

2224

2527

2830

Selecting research scholar and procuring of chemicals and instruments and literature survey followed by establishment of lab and research experiments 9


3133

3336


2

Crystallization, characterization of new solid forms

3

Solubility and stability behavior of new solid forms

4

Patent registration in India and continuation of the projects to produce more materials for other studies and optimization

5

Cell culturing and collaboration for biological studies

6

Consolidation of reports for global patents/publication

3.3. Suggested plan of action for utilization of research outcome expected from the Project: The research outcome from the present project will be utilized to design new families of drugs with the improved solubility and stability properties. Once the properties are developed for any drugs which we take in this project will be recommended for the marketing and industrial R and D units in India for commercial use. The patent for that developed drug will be filled with prior permission from DST SERB. This project will have dual advantages Industry and academic applications in terms of structure property relationship. Finally, the research methodology and the research setup will be utilized for a full fledge of research activity in a wider crystal engineering research area. Further, this study of all these characterization methods and drug materials will help us in understanding structure-property relationships well. 3.4. Environmental impact assessment and risk analysis: None.

4. Expertise 10



4.1. Expertise available with the investigators in executing the project: The principal investigator Dr. S. Sudalai Kumar has trained well in organic synthesis, separation, purification and characterization of organic molecules using TLC and column chromatography and various spectroscopic techniques like FT-IR, Raman, NIR, 1H-NMR, 13

C-NMR. He is strong in the analysis of different crystalline forms (polymorphs, solvates,

hydrates, salts and cocrystals) using X-ray diffraction methods (both single crystal XRD and Powder XRD) and Differential Scanning Calorimetry (DSC), Thermal Gravimetric Analysis (TGA), Hot Stage Microscopy (HSM), and FT-IR, NIR, Raman spectroscopy and ss-NMR spectroscopy. He has hands-on experience with SMART APEX CCD X-ray diffractometer, Xcalibur Gemini Eos CCD X-ray diffractometer, crystal structure solution and refinement, determination, Bruker 400 MHz NMR spectrometer, Thermo Nicolet 6700 FT-IR and Raman spectrometer, Thermo Scientific Evolution 300 UV-VIS Spectrometer, Metler Toledo DSC/TGA instruments, Wagner Munz Hot stage microscope, Electrolab Dissolution Tester, Retsch MM 400 ball mill grinder. He has sound knowledge of various softwares such as Polymorph Prediction CSD (CCDC-Cambridge Crystallographic Data Centre) for crystal structure database analysis, SAINT, SHELX-TL, CrysAlisPro 171.33.55, Olex2-1.0, WinGX, Platon for crystal structure solution and refinement, Mercury & XSeed for viewing and graphics, Powder Cell 2.4 for fingerprint match and quantification of polymorphic phases and least squares refinement, Crystal Explorer (Hirshfeld Surface Analysis) for analyzing intermolecular interactions and polymorphism in molecular crystals, XPac to compare crystal structures of similar/dissimilar. The model compounds and drugs studied in his PhD thesis work belong to the broad category of drug classification such as sulfonamides, amphoteric compounds, amino acids, antifungal azole drugs, sulfonylureas, fibrates and fenamates and hence he could explore the same structure-property relationship for these many numbers of drugs in each of these categories. The idea of expanding the study of polymorph screening and crystal engineering strategies to the other drugs in the same category using different crystallization conditions would provide interesting directions to solve the pharmaceutical and developmental challenges in drug industries for him.

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The Co-Investigators Dr. D. Kodimunthiri and Mr. M. Kannan are also having experience in synthesis and characterization of different materials. Both of them will assist the project in the analysis, experimental and publications of works. 4.2 Summary of roles/responsibilities for all investigators: All the technical as well as academic responsibilities will be taken care of by P. I. alone. This include planning, facility installation, training to JRF, measurements, data analysis and comparison. He will take care of publishing the works in national and international publications even in filling patents with the help of two investigators. They would seek some industrial units in India to complete the successful marketing of the develped drug for commercial use. 4.3 Key publications published by the investigators pertaining to the theme of the proposal during the last 5 years: Publications of PI: Dr. Sudalai Kumar, Assistant Professor, Department of Chemistry Francis Xavier Engineering College, Vannarpettai, Tirunelveli-627003. 1.

Neutral

and

Zwitterionic

Polymorphs

of

2-(p-Tolylamino)nicotinic

Acid.

N. K. Nath, S. Sudalai Kumar and A. Nangia Cryst. Growth & Des., 2011, 11, 4594. (IUCr best poster award in ICCOSS 2011 conference) 2.

Pharmaceutical Cocrystals of Niclosamide. P. Sanphui,

S. Sudalai Kumar and A.

Nangia Cryst. Growth & Des., 2012, 12, 4588. 3.

Solid-state

Form

Screen

of

Cardiosulfa

and

Its

Analogs.

S. Sudalai Kumar, S. Rana and A. Nangia Chem. Asian J. 2013, 8, 1551. 4.

A new Conformational Polymorph of N-acetyl-L-cysteine, The role of S–H···O and C– H···O interactions. S. Sudalai Kumar and A. Nangia CrystEngComm, 2013, 15, 6498.

5.

Pharmaceutical

Cocrystals

and

a

Nitrate

Salt

of

Voriconazole

S. Sudalai Kumar, R. Thakuria and A. Nangia CrystEngComm, 2014, 16, 4722. Special Theme issue of CEC on India IYCr 2014 Celebration. 6.

A Solubility Comparison of Neutral and Zwitterionic Polymorphs. S. Sudalai Kumar and A. Nangia Cryst. Growth & Des., 2014, 14, 1865. Virtual special issue IYCr 2014 Celebrating the International Year of Crystallography.

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7.

New Pharmaceutical Salts of Gliclazide, Clonixin and Clofibric acid S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.2051.7282.

8.

Crystal

Structure

of

Benzydamine

Hydrochloride

Salt,

S. Sudalai

Kumar,

Researchgate.net, 2015, DOI: 10.13140/RG.2.1.1600.9128/1. 9.

Crystal Structure of Ethamivan Drug, S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.4099.6009.

10.

A Review: Structure-Solubility-Stability Relationships: Solid State Forms of Active Ingredients,

S.

Sudalai

Kumar,

Researchgate.net,

2015,

DOI:

10.13140/RG.2.1.3839.2165. 11.

Social Analysis of RTI act 2005-Its failure in India, S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.2173.2327.

12.

Zwitterionic and Neutral Polymorphs of Amphoteric Drugs, S. Sudalai Kumar, Kranti Kumar and Ashwini Nangia (MS in preparation).

13.

Pharmaceutical Salts of Niflumic Acid, M. Sudhir, S. Sudalai Kumar and A. Nangia (MS in preparation).

14.

Pharmaceutical Cocrystals of Zolpidem, S. Sudalai Kumar, Naba K. Nath and A. Nangia (MS in preparation).

15.

Social Analysis of Indian PhD Education - A Skilled Slavery, S. Sudalai Kumar, Researchgate.net, 2015 (MS in preparation).

Publications of Co-PIs: Kannan Masanam, DEPARTMENT OF CHEMISTRY, THIRUVALLUVAR COLLEGE, PAPANASAM, VICKRAMASINGAPURAM, TIRUNELVELI DISTRICT, TAMILNADU 627 425. 1. T. Punniyamurthy and M. Kannan, “Polyaniline” e-EROS Encyclopedia of Reagents for Organic Synthesis, 2012. 2. M. Kannan and T. Punniyamurthy, “Effect of Ligand N,N-Substituents on the Reactivity of Chiral Copper(II) Salalen, Salan and Salalan Complexes Towards Asymmetric Nitroaldol Reaction” Tetrahedron:Asymmetry, 2014, 25, 1331. 3.

G. Bharathiraja, M.Sengoden, M. Kannan and T. Punniyamurthy, “Expedient Synthesis of Tetrasubstituted Pyrroles via Copper-Catalyzed Cascade Inter-/Intramolecular Cyclization of 1,3Enynes Carry a Nitro Group with Amines” Org. Biomol. Chem. 2015, 13, 2786.

4. M. Kannan, M. Sengoden and T. Punniyamurthy, "Transition-Metal-Mediated Carbon-Heteroatom Cross-Coupling. An Overview" in Arene Chemistry: Reaction Mechanisms and Methods for 13



Aromatic Compounds (Book Chapter) Ed: J. Mortier, Wiley, 2015.

Publications of Co-PIs: 2. Dr. D. Kodimunthiri, Assistant Professor, Department of Chemistry ( Francis Xavier Engineering College, Vannarpettai, Tirunelveli-627003. 1. D. Kodimunthiri, P. Tharmaraj*, C.D. Sheela and P. Prakash, Bis-(3,5-dimethyl-pyrazolyl-1methyl)-(3-phosphanyl-propyl)-amine complexes of copper(II), nickel(II), and cobalt(II) J. Coord. Chem., 62, 1347 (2009). (*Corresponding author) 2. D. Kodimunthiri, P. Tharmaraj*, C.D. Sheela, C.S. Shanmuga Priya, Synthesis, Spectral characterization and Antimicrobial Activity of Copper(II), Cobalt(II) and Nickel(II) complexes of 3-Formylchromoniminopropylsilatrane, J. Coord. Chem., 62, 2220 (2009). (*Corresponding author) 3. D. Kodimunthiri, P. Tharmaraj*, C.D. Sheela and C.S. Shanmuga priya Synthesis, spectral studies and

antibacterial

activity

of

Cu(II),

Co(II)

and

Ni(II)

complexes

of

2-{1-[(3,5-

dimethylpyrazolylmethyl)-hydrazono]-3-phenyl-allyl}-phenol, J. Serb. Chem. Soc., 74 (8–9) 927 (2009). (*Corresponding author) 4. D. Kodimunthiri, P. Tharmaraj, C.D. Sheela and P. Prakash, Catalytic and biological activity of transition metal Complexes of salicylaldiminopropylphosphine, J. Coord. Chem., 2009, 62, No. 17, 2883 (2009). (*Corresponding author) 5. C. Dorthy Sheela*, C. Anitha, D. Kodimunthiri, and

P. Tharmaraj, Synthesis, Spectral

Characterisation and Antimicrobial Studies of Metal Complexes of Schiff Base derived from [4amino-N-guanylbenzene sulfonamide] and Salicylaldehyde, J. Coord. Chem., 63, No. 5, 884 (2010). (*Corresponding author) 6. R. Ebenezer, C.D. Sheela, P. Tharmaraj, D. Kodimunthiri. Synthesis, Spectral Characterization and Biological Activity of Vanillin Substituted Silane Schiff Base, International Journal of Emerging Trends in Pharmaceutical Sciences, Volume 1, Issue 2, March 2013.

7. M. Kalanithi, D. Kodimunthiri, M. Rajarajan, P. Tharmaraj, Synthesis, characterization and biological activity of some new VO(IV), Co(II),Ni(II), Cu(II) and Zn(II) complexes of chromone based NNO Schiff base derived from 2-aminothiazole, Spectrochimica Acta Part A 82 (2011) 290– 298. 8.

14



4.4 Bibliography: [1] M. A. Neumann, J. van de Streek, F. P. A. Fabbiani, P. Hidber and O. Grassmann, Nature Commun., 2015, DOI: 10.1038/ncomms8793. [2] (a) G. R. Desiraju, Crystal Engineering: The Design of Organic Solids; Elsevier: Amsterdam, 1989; (b) J. Dunitz and J. Bernstein Acc. Chem. Res., 1995, 28, 193. [3]

. L pez-Mejías and A. J. Matzger, Cryst. Growth Des., 2015, 15, 3955.

[4] A. Delori, P. Maclure, R. M. Bhardwaj, A. Johnston, A. J. Florence, O. B. Sutcliffe and I. D. H. Oswald, CrystEngComm, 2014, 16, 5827. [5] S. Cherukuvada and A. Nangia, Chem. Commun., 2014, 50, 906. [6] S. S. Kumar, S. Rana and A. Nangia Chem. Asian J. 2013, 8, 1551. [7] N. Blagden, M. de Matas, P. T. Gavan and P. York, Adv. Drug Deliv. Rev., 2007, 59, 617. [8] (a) M. K. Nazeeruddin, A. Kay, I. Rodicio, R. Humphry-Baker, E. Muller, P. Liska, N. Vlachopoulos and M. Gr_tzel, J. Am. Chem. Soc., 1993, 115, 6382; (b) C.-H. Zhao, A. Wakamiya, Y. Inukai and S. Yamaguchi, J. Am. Chem. Soc., 2006, 128, 15934; (c) T. Mutai, H. Tomoda, T. Ohkawa, Y. Yabe and K. Araki, Angew. Chem. 2008, 120, 9664; Angew. Chem. Int. Ed. 2008, 47, 9522; (d) B.-K. An, S. H. Gihm, J. W. Chung, C. R. Park, S.-K. Kwon and S. Y. Park, J. Am. Chem. Soc., 2009, 131, 3950. [9] (a) W.C. McCrone, Polymorphism. In Physics and Chemistry of the Organic Solid State, Vol. II (ed. D. Fox, M. M. Labes and W. A.), Interscience, 1965; (b) W.C. McCrone, Polymorphism. Phys. Chem. Org. Solid State 2, 1965, 725; (c) W.C. McCrone, Microscopy held to be prime problem-solver. Quality Assurance, 1965. [10] R. Hilfiker, Polymorphism: In the Pharmaceutical Industry, John Wiley and Sons, 2006. [11] (a) S. R. Chemburkar, J. Bauer, K. Deming, H. Spiwek, K. Patel, J. Morris, R. Henry, S. Spanton, W. Dziki, W. Porter, J. Quick, P. Bauer, J. Donaubauer, B. A. Narayanan, M. Soldani, D. Riley and K. McFarland, Org. Process Res. Dev., 2000, 4, 413. [12] (a) F. Rodriguez-Caabeiro, A. Criado-Fornelio, A. Jimenez-Gonzalez, L. Guzman, A. Igual, A. Perez and M. Pujol, Chemotherapy, 1987, 33, 266; (b) V. López-Mejías, J. Kampf and A. Matzger, J. Am. Chem. Soc 2012, 134, 9872. [13] (a) S. Thirunahari, S. Aitipamula, P. S. Chow and R. B. H. Tan, J. Pharm. Sci. 2010, 99, 2975; (b) N. K. Nath and A. Nangia, CrystEngComm, 2010, 13, 47. [14] N. K. Nath, S. S. Kumar and A. Nangia, Cryst. Growth Des. 2011, 11, 4594.

15



[15] N. J. Babu, S. Cherukuvada, R. Thakuria and A. Nangia, Cryst. Growth Des., 2010, 10, 1979. [16] (a) S. Basavoju, D. Bostrom and S. P. Velaga, Cryst. Growth Des., 2006, 6, 2699; (b) R. Barbas, R. Prohens and C. J. Puigjaner, Thermal Anal. Calorim. 2007, 89, 687 [17] G. R. Desiraju, Cryst. Growth Des., 2008, 8, 3. [18] S. S. Kumar and A. Nangia Cryst. Growth Des. 2014, 14, 1865. [19] V. López-Mejías, J. Kampf and A. Matzger, J. Am. Chem. Soc 2012, 134, 9872. [20] M. Vasileiadis, A. V. Kazantsev, P. G. Karamertzanis, C. S. Adjiman and C. C. Pantelides, Acta Crystallogra., 2012, B68, 677. [21] C. R. Groom and F. H. Allen, Angew. Chem. Int. Ed., 2014, 53, 662. [22] G. M. Day, A. V. Trask, W. D. S. Motherwell and W. Jones Chem. Commun., 2006, 54. [23] (a) A. V. Trask, W. D. S. Motherwell and W. Jones, Chem. Commun., 2004, 890; (b) A. V. Trask, W. D. S. Motherwell and W. Jones, Cryst. Growth Des., 2005, 5, 1013. [24] A. R. Buist, A. R. Kennedy, K. Shankland, N. Shankland and M. J. Spillman, Cryst. Growth Des., 2013, 13, 5121. [25] J. M. Miller, B. M. Collman, L. R. Greene, D. J. W. Grant and A. C. Blackburn, Pharm. Dev. Technol. 2005, 10, 291. [26] D. J. Berry, C. C. Seaton, W. Clegg, R. W. Harrington, S. J. Coles, P. N. Horton, M. B. Hursthouse, R. Storey, W. Jones, R. Friscic and N. Blagden, Cryst. Growth Des. 2008, 8, 1697. [27] J. Bernstein, Polymorphism in Molecular Crystals, Oxford University Press, 2002. [28] N. K. Nath, S. Nilapwar and A. Nangia Cryst. Growth Des., 2012, 12, 1613. [29] D. Braga, F. Grepioni, L. Maini, M. Polito, K. Rubini, M. R. Chierotti, and R. Gobetto, Chem. Eur. J., 2009, 15, 1508. [30] S. L. Childs, L. J. Chyall, J. T. Dunlap, D A. Coates, B. C. Stahly and G. P. Stahly, Cryst. Growth Des., 2004, 4, 441. [31] E. H. Lee, S. X. M. Boerrigter , A. C. F. Rumondor, S. P. Chamarthy and S. R. Byrn Cryst. Growth Des., 2008, 8, 91. [32] C. P. Price, A. L. Grzesiak and A. J. Matzger, J. Am. Chem. Soc. 2005, 127, 5512. [33] H. Jeong-Myeon, J. H. Wolf, M. A. Hillmyer and M. D. Ward Chem. Soc. Rev., 2014, 43, 2066. [34] A. Y. Lee, A. Ulman and A. S. Myerson, Langmuir, 2002, 18, 5886. 16



[35] (a) J. F. Kang, J. Zaccaro, A. Ulman, A. S. Myerson, Langmuir, 2000, 16, 3791; (b) C. A. Mitchell, L. Yu and M. D. Ward J. Am. Chem. Soc., 2001, 123,10830. [36] (a) M. Lackinger, S. Griessl, W. M. Heckl, M. Hietschold and G. W. Flynn, Langmuir, 2005, 21, 4984; (b) J.-H. An, J.-M. Kim, S.-M. Chang and W.-S. Kim, Cryst. Growth Des., 2010, 10, 3044; [37] (a) B. A. Garetz, J. E. Aber, N. L. Goddard, R. G. Young and A. S. Myerson, Phys. Rev. Lett.,1996, 77, 3475; (b) W. I. Cross, N. Blagden and R. J. Davey, Cryst. Growth Des., 2003, 3, 151 [38] I. Kuzmenko, H. Rapaport, K. Kjaer, J. Als-Nielsen, I. Weissbuch, M. Lahav and L. Leiserowitz, Chem. Rev., 2001, 101, 1599. [39] I. Weissbuch, L. Addadi, Z. Berkovitch-Yellin, E. Gati, M. Lahav and L. Leiserowitz, Nature 1984, 310, 161. [40] A. T. Hulme, S. L. Price and D. A. Tocher J. Am. Chem. Soc., 2005, 127, 1116. [41] W. I. Cross, N. Blagden and R. J. Davey, Cryst. Growth Des., 2003, 3, 151. [42] Cambridge Structural Database, ver. 5.31, ConQuest 1.13, November 2013 release, Cambridge Crystallographic Data Center; www.ccdc.cam.ac.uk. [43] S. Aitipamula, P. S. Chow and R. B. H. Tan CrystEngComm, 2014, 16, 3451. [44] (a) M. K. Mishra, P. Sanphui, U. Ramamurty and G. R. Desiraju, Cryst. Growth Des. 2014, 14, 3054; (b) M. K. Mishra, S. Varughese, U. Ramamurty and G. R. Desiraju, J. Am. Chem. Soc., 2013, 135, 8121. [45] S. Cherukuvada and A. Nangia Chem. Commun., 2014, 50, 906. [46] (a) S. Aitipamula, R. Banerjee, A. K. Bansal, K. Biradha, M. L. Cheney, A. R. Choudhury, G. R. Desiraju, A. G. Dikundwar, R. Dubey, M. Duggirala, P. P. Ghogale, S. Ghosh, P. K. Goswami, N. R. Goud, R. K. R. Jetti, P. Karpinski, P. Kaushik, D. Kumar, V. Kumar, B. Moulton, A. Mukherjee, G. Mukherjee, A. S. Myerson, V. Puri, A. Ramanan, T. Rajamannar, C. M. Reddy, N. Rodriguez-Hornedo, R. D. Rogers, T. N. G. Row, P. Sanphui, N. Shan, G. Shete, A. Singh, C. C. Sun, J. A. Swift, R. Thaimattam, T. S. Thakur, R. K. Thaper, S. P. Thomas, S. Tothadi, V. R. Vangala, N. Variankaval, P. Vishweshwar, D. R. Weyna and M. J. Zaworotko, Cryst. Growth Des., 2012, 12, 2147; (b) S. Ghosh and C. M. Reddy Angew. Chem. Int. Ed., 2012, 51, 10319. [47] (a) P. A. Jadhav, V. T. Deshmukh, P. S. Patil and S. C. Dhawale, Curr. Pharma Res., 2011, 2, 432; (b) N. J. Babu and A. Nangia, Cryst. Growth Des., 2011, 11, 2662. 17



[48] (a) G. R. Desiraju, Crystal Design: Structure and Function. Edited by Gautam R. Desiraju, John Wiley & Sons, Ltd, Volume 7, 2003. [49] (a) F. Lovering, J. Bikker and C. J. Humblet, Med. Chem., 2009, 52, 6752; (b) A. Gavezzotti, J. Chem. Soc., Perkin Trans. 2, 1995, 1399; (c) R.-M. Dannenfelser and S. H. Yalkowsky, Ind. Eng. Chem. Res. 1996, 35, 1483. [50] I. Weissbuch, R. Popovitz-Biro, M. Lahav and L. Leiserowitz, Acta Crystallogr. 1994, B51, 115. [51] R. L. White-Morris, M. M. Olmstead and A. L. Balch, J. Am. Chem. Soc., 2003, 125, 1033. [52] S. S. Kumar, PhD thesis 2014, Researchgate.net. DOI: 10.13140/RG.2.1.4054.6729, 10.13140/2.1.1640.2563. [53] C. K. Smith and L. Regan, Science 1995, 270, 980. [54] (a) G. R. Desiraju, Crystal Engineering: The Design of Organic Solids; Elsevier: Amsterdam, 1989; (b) N. Blagden, M. de Matas, P. T. Gavan and P. York, Adv. Drug Deliv. Rev., 2007, 59, 617. [55] M. A. Neumann, J. van de Streek, F. P. A. Fabbiani, P. Hidber and O. Grassmann, Nature Commun., 2015, DOI: 10.1038/ncomms8793. [56] R. Thakuria, M. D. Eddleston, E. H. H. Chow, G. O. Lloyd, B. J. Aldous, J. F. Krzyzaniak, A. D. Bond and W. Jones, Angew. Chem., Int. Ed., 2013, 52, 10541. [57] I. G. Goldberg and J. A. Swift, Cryst. Growth Des., 2012, 12, 1040. [58] A. Delori, P. Maclure, R. M. Bhardwaj, A. Johnston, A. J. Florence, O. B. Sutcliffe and I. D. H. Oswald, CrystEngComm, 2014, 16, 5827. [59] R. Hilfiker, Polymorphism: In the Pharmaceutical Industry, John Wiley and Sons, 2006. [60] (a) C. B. Aakeröy and D. J. Salmon, CrystEngComm 2005, 7, 439; (b) B. R. Bhogala, S. Basavoju and A. Nangia, CrystEngComm 2005, 7, 551; (c) J. A. Bis, O. L. McLaughlin, P. Vishweshwar and M. J. Zaworotko, Cryst. Growth Des. 2006, 6, 2648; (d) F. H. Allen, V. J. Hoy, J. A. K. Howard, V. R. Thalladi, G.R. Desiraju, C. C. Wilson, G. J. McIntyre, J. Am. Chem. Soc. 1997, 119, 3477. [61] (a) G. R. Desiraju, J. J. Vittal and A. Ramanan, Crystal Engineering: A Textbook, World Scientific, 2011; (b) N. R. Goud, K. Suresh, P. Sanphui and A. Nangia, Int. J. Pharm., 2012, 439, 63. [62] (a) C. B. Aakeröy, D. J. Salmon, CrystEngComm 2005, 7, 439; (b) B. R.Bhogala, S. Basavoju, A. Nangia, CrystEngComm, 2005, 7, 551; (c) J. A. Bis, O. L. McLaughlin, P. Vishweshwar, M. J. Zaworotko, Cryst. Growth Des. 2006, 6, 2648; F. H. Allen, V. J. Hoy, 18



J. A. K. Howard, V. R. Thalladi, G.R. Desiraju, C. C. Wilson, G. J. McIntyre, J. Am. Chem. Soc. 1997, 119, 3477.

5. List of Projects Submitted/Implemented/Completed by the Investigators 5.1 Details of projects under implementation/completion: S.No

Title

Cost in lakh/Name

Duration

of the project 1

Pharmaceutical

JC Bose fellowship

CSIR

CSIR Fellowship

Agency

PI/Co-PI 3 years

solid forms 2

Role as

3 years

Pharmaceutical

CSIR-JRF

DST SERB

and SRF

(completed)

CSIR-JRF

CSIR (completed)

and SRF

Cocrystals 3

Novel Solid-

UGC (PURSE

state Forms of

grant)

3 years

PhD Scholar

UGC (completed)

APIs 4

Sythesis of

UGC summer

Nicotinic acid

project

2 months

Project

UGC

student

(completed)

derivatives

6. List of Facilities Being Extended by Parent Institution(s) for the Project Implementation 6.1 Infrastructure Facilities: Sr. No. 1

Infrastructure Facility

Yes/No/Not required

Workshop Facility

Yes

2

Water & Electricity

Yes

3

Laboratory Space/Furniture

Yes

4

Power Generator

Yes

5

AC Room/AC

Yes

19



6

Telecommunication including e-mail & fax

Yes

7

Transportation

Yes

8

Administrative/Secretarial support

Yes

9

Information facilities like Internet/Library

Yes

10

Computational facilities

Yes

11

Animal/glass house

Not required

12

Any other special facility being provided

Not required

6.2 Equipment Available with the Institute/Group/Department/Other Institutes for the project: Equipment available

Generic Name of Equipment

Model, Make & year of purchase

with PI & his group

PI's Department

Flame Photometer Spectrophotometer Ultrasonic Interferometer Methanol Fuel Cell UV-Visible spectrophotometer Atomic Absorption Spectroscopy Gas Chromatography X-ray Diffractometer (Powder and single crystal diffractometer)

University of Hyderabad

Solid state NMR UV/Vis spectrometer

Laboratory of Magnetic Resonance Spectroscopy & Imaging

Solid state 13C and 15N cross-polarization/magic angle spinning (CP/MAS)

20

Deep Vision 1382 EFOY 1200 Deep Vision 371 Thermoscientific AA 301 Thermoscientific Trace 1110 Bruker (VT-PXRD) and Oxford in 2010

Remarks including accessories available and current usage of equipment Working Working Working Working Working Working Working

Bruker Advance spectrometer operating at 400 MHz (100 MHz for 13C nucleus) in 2009

Working

Thermo Scientific Evolution EV300 UV/Vis spectrometer (Waltham, MA) in 2008

Working

Bruker AVANCE III-500 spectrometer (Bruker BioSpin, Karlsruhe, Germany

Working



China Thiruvalluvar Rotavapour, Condensers, Arts College UV chamber, Water Papanasam Bath, Fume hood and Nitrogen cyllinders

7. Name and Address

-

Working

of Experts/Institutions

Interested in the

Subject/Outcome of the Project 1. Prof. G. R. Desiraju Solid state Research Centre Indian Institute of Science Bangalore-560 012. Email: [email protected] 2. Prof. Ashwini Nangia National Chemical Laboratory Pune, Maharastra-411008. Email: [email protected] 3. T. N. Guru Row Solid state Research Centre Indian Institute of Science Bangalore-560 012. Email: [email protected]. 4. C. Malla Reddy Department of Chemistry Indian Institute of Science Education And Research Kolkata Kolkata-741 246. Email: [email protected].

21


Budget Summary

Budget Details

Full Summary (in Rs.) Institute

Manpower Budget

Francis Xavier Engineering College, TIRUNELVELI

11,08,800

Total

11,08,800

Consumables

Travel

Equipment

Contingencie Other Overh s Costs ead Costs

Total

90,000

1,20,000

25,91,200

90,000

5,00,0 5,00,0 00 00

50,00,000

90,000

1,20,000

25,91,200

90,000

5,00,0 5,00,0 00 00

50,00,000

Manpower Budget Breakup Institute Name :

Francis Xavier Engineering College, TIRUNELVELI

Summary : Budget Head Manpower Budget

Year-1 Amt (in Rs.)

Year-2 Amt (in Rs.)

Year-3 Amt (in Rs.)

Total (in Rs.)

3,60,000

3,60,000

3,88,800

11,08,800

Consumables

30,000

30,000

30,000

90,000

Travel

60,000

30,000

30,000

1,20,000

25,91,200

0

0

25,91,200

30,000

30,000

30,000

90,000

Other Costs

3,00,000

1,00,000

1,00,000

5,00,000

Overhead Costs

2,00,000

2,00,000

1,00,000

5,00,000

35,71,200

7,50,000

6,78,800

50,00,000

Equipment Contingencies

Grand Total (in Rs.) Manpower Budget Detail : Designation JRF Justification for Manpower :

Year-1 Amt (in Rs.) 3,60,000

Year-2 Amt (in Rs.) 3,60,000

Year-3 Amt (in Rs.) 3,88,800

Total Amt (in Rs.) 11,08,800

1 . A young bright NET/GATE qualified M. Sc. Physics student is required to conduct the synthesis, characterization and other necessary experimental works. The position requested is a JRF with a pay of as per DST rule. A portion of this project will form a part of his/her thesis work.

Consumable Cost Detail : Year-1 Amt (in Rs.)

Year-2 Amt (in Rs.)

30,000

Year-3 Amt (in Rs.)

30,000

Total Amt (in Rs.)

30,000

90,000

Justification for Consumables : 1 . Glasswares for solid state synthesis, Drug materials for solid form screening and mortar and pestle for grinding will be ordered from this budget.

Travel Cost Detail : Travel

Year-1 Amt (in Rs.)

Inland travel

Year-2 Amt (in Rs.)

60,000

Year-3 Amt (in Rs.)

30,000

Total Amt (in Rs.)

30,000

1,20,000

Justification for Travel : 1 . Travel grant is required for regular visit to single crystal XRD and ss NMR facility centres in India. In addition, travel grant will also be utilized for attending conferences, seminars etc.

Equipment Cost Detail : Generic Name

make

Model Quanti Estimated ty Cost in INR

Estimated Cost in Foreign Currency

Foreign Exchange Rate

Spare time for other users (in %)

Powder XRD

Germany

D2 PHAS ER Bruker

1

5,91,200

0

0

40

Dissolution Tester

India

TDT- 0 8L

1

5,00,000

0

0

30

FTIR

Japan

IR Affinity 1Shima dzu)

1

10,00,000

0

0

25

UV-Visible Spectrophotometer

Japan

UV1800Shima dzu

1

5,00,000

0

0

25

Justification for Equipments : 1 . For the confirmation of new phases in solid state synthesis. 2 . It is mainly used for the determination of dissolution rate of drug materials (IDR). 3 . Its a primary tool to confirm the solid form formation. 4 . It is needed for performing the solubility experiments.

Contingency Cost Detail : Year-1 Amt (in Rs.)

Year-2 Amt (in Rs.)

30,000

Year-3 Amt (in Rs.)

30,000

30,000

Total Amt (in Rs.) 90,000

Justification for Contingency : 1 . In executing the project, a budget for contingencies is required to buy small laboratory items, electric components, furniture, stationary items, postage, books and allied items etc.

Other Cost Detail : Other Cost

Year-1 Amt (in Rs.)

500000

3,00,000

Year-2 Amt (in Rs.) 1,00,000

Year-3 Amt (in Rs.)

Total Amt (in Rs.)

1,00,000

5,00,000

Justification for Other Cost : 1 . Computers, printers, melting point apparatus, Roto vapor, and scanners and some other miscellaneous instruments required for chemical synthesis.

Overhead Detail : Year-1 Amt (in Rs.)

Year-2 Amt (in Rs.)

2,00,000

2,00,000

Year-3 Amt (in Rs.) 1,00,000

Total Amt (in Rs.) 5,00,000

Justification for Overhead : 1 . Overhead amount is require as a part of the project budget towards meeting the costs for overhead expenses including infrastructure facilities etc. The amount of Rs. 5 Lakhs is quoted as per DST guidelines.

RTGS Details :

Comments :

Fresh quotations have been requested from different suppliers and waiting for their reply. It will updated to DST SERB once we received them on or before short listing the proposal.

Name of Account Holder :

St Xavier Educational Trust

Email ID :

[email protected]

Designation :

Principal

Account Number :

438676107

Bank Name :

Indian Bank

Branch Name and Address :

Post Box No 39-84 Thiruvanathapuram road Tirunelveli 627002

IFSC Code :

IDIB000P008

Any other relevant matter : Third Co Investigator Dr. D. Kodimunthiri, Assistant Professor, Department of Chemistry, Francis Xavier Engineering College, Vannarpettai, Tirunelveli-627003. Mail Id: [email protected] Suitability of the proposed work in the major national initiatives of the Government : SNo.

Program Name

1

Startup India

Dr. S. Sudalai Kumar Present Address Department of Chemistry (S and H) Francis Xavier Engineering College Tirunelveli 627 003, TN (India) Mail id: [email protected]

Gender : DOB : Marital Status: Mobile :

Male 13th May, 1987 Single +91 9952885464

Academic Qualification 2015 – Present Assistant Professor of Engineering Chemistry and Environmental Science and Engineering, Department of Science and Humanities, Francis Xavier Engineering College (affiliated to Anna University, Chennai), Scad Group of Institutions, Tirunelveli, Tamil Nadu, India. 2009 – 2015

Ph.D. in Supramolecular Chemistry and Crystal Engineering (Chemistry), School of Chemistry, University of Hyderabad, Hyderabad, AP, India.

2007 – 2009

M. Sc. (Chemistry), Department of Chemistry, RKM Vivekananda College, University of Madras, Chennai, Tamil Nadu, India.

2004 – 2007

B. Sc. (Chemistry), St. Xavier’s College, Manonmaniam Sundaranar University, Tirunelveli, Tamil Nadu, India. CSIR-NET (59th rank) qualified for Professorship as per UGC/AICTE norms.

2009

List of Publications 1.

Neutral

and

Zwitterionic

Polymorphs

of

2-(p-Tolylamino)nicotinic

Acid.

N. K. Nath, S. Sudalai Kumar and A. Nangia Cryst. Growth & Des., 2011, 11, 4594. (IUCr best poster award in ICCOSS 2011 conference) 2.

Pharmaceutical Cocrystals of Niclosamide. P. Sanphui, S. Sudalai Kumar and A. Nangia Cryst. Growth & Des., 2012, 12, 4588.

3.

Solid-state

Form

Screen

of

Cardiosulfa

and

S. Sudalai Kumar, S. Rana and A. Nangia Chem. Asian J. 2013, 8, 1551.

Its

Analogs.

4.

A new Conformational Polymorph of N-acetyl-L-cysteine, The role of S–H···O and C– H···O interactions. S. Sudalai Kumar and A. Nangia CrystEngComm, 2013, 15, 6498.

5.

Pharmaceutical

Cocrystals

and

a

Nitrate

Salt

of

Voriconazole

S. Sudalai Kumar, R. Thakuria and A. Nangia CrystEngComm, 2014, 16, 4722. Special Theme issue of CEC on India IYCr 2014 Celebration. 6.

A Solubility Comparison of Neutral and Zwitterionic Polymorphs. S. Sudalai Kumar and A. Nangia Cryst. Growth & Des., 2014, 14, 1865. Virtual special issue IYCr 2014 Celebrating the International Year of Crystallography.

7.

New Pharmaceutical Salts of Gliclazide, Clonixin and Clofibric acid S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.2051.7282.

8.

Crystal Structure of Benzydamine Hydrochloride Salt, S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.1600.9128/1.

9.

Crystal Structure of Ethamivan Drug, S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.4099.6009.

10.

Structure-Solubility-Stability Relationships: Solid State Forms of Active Ingredients, S. Sudalai Kumar, Researchgate.net, 2015, DOI: 10.13140/RG.2.1.3839.2165.

11.

Zwitterionic and Neutral Polymorphs of Amphoteric Drugs, S. Sudalai Kumar, Kranti Kumar and Ashwini Nangia (MS in preparation).

12.

Pharmaceutical Salts of Niflumic Acid, M. Sudhir, S. Sudalai Kumar and A. Nangia (MS in preparation).

13.

Pharmaceutical Cocrystals of Zolpidem, S. Sudalai Kumar, Naba K. Nath and A. Nangia (MS in preparation).

14.

Social Analysis of Indian PhD Education - A Skilled Slavery, S. Sudalai Kumar, Researchgate.net, 2015 (MS in preparation).

15.

Social Analysis of RTI act 2005-Its failure in India, S. Sudalai Kumar, Researchgate.net, 2015, DOI:10.13140/RG.2.1.2173.2327.

Awards and Achievements 1.

Delivered a flash presentation on the topic of Structure Property Correlation of Neutral and Zwitterionic Polymorphs in K. V. Rao Award 2014 at University of Hyderabad, India.

2.

Delivered a flash presentation on the topic of Comparison of Stability and Solubility of Neutral, Zwitterionic and Conformational Polymorphs in ChemFest 2014 at University of Hyderabad, India.

3.

Delivered a flash and poster presentation on the topic of Polymorph Screen and Characterization of Cardiosulfa and Its Analogs in ICCOSS 2013 at University of Oxford, Oxford, UK.

4.

Poster presentation on the topic of Characterization of Isostructural Solid Forms of APIs in MED-CHEM 2013 conference held at IIT-Madras, India.

5.

Poster presentation on the topic of Characterization of Isostructural Solid Forms of APIs in AP Science Congress Meet 2013 conference held at University of Hyderabad, India.

6.

Poster presentation on the topic of Solid-state Forms of Cardiosulfa and Its Analogs in ChemFest 2012 conference held at University of Hyderabad, India.

7.

Poster presentation on the topic of Solid-state Forms of Cardiosulfa and Its Analogs in INDO-US 2012 conference held at IIT-Delhi.

8.

IUCr best poster award in the presentation on the topic of Neutral and Zwitterionic Polymorphs of 2-(p-Tolylamino)nicotinic acid (TNA) in international conference ICCOSS 2011 held in IISc Bangalore.

9.

Poster presentation and participation on the topic of Solid-state Forms of Cardiosulfa and Its Analogs in IYC 2011 conference and Science exhibition, demonstration and participation in IYC 2011 program at School of chemistry, University of Hyderabad, India.

10.

Participation in FDP and FOP 2015 (faculty development program and orientation program for Asst. Professors) at Scad Group of Institutions, Tirunelveli, Tamil Nadu, India.

Research Experience 1.

Antibacterial activity study of drugs in Department of Plant sciences, University of Hyderabad, Hyderabad, India.

2.

Summer Research Project May-June 2009, School of Chemistry, University of Hyderabad.

3.

Summer Research Project 2008, Department of Organic Chemistry, University of Madras, Chennai.

4.

Analysis of Ground Water 2008, Institute for Water Analysis, PWD, Government of Tamil Nadu, Chennai.

5.

Chemist in Drug production 2007, Orchid Chemicals and Pharmaceuticals, Chennai.

6.

Student Chemist in QC 2006, Savita Chemicals Pvt. Ltd, Mumbai.

Research Interests With a sound background on preparation, crystallization and characterization of solid state forms of model organic compounds and active pharmaceutical ingredients, I would like to carry out further research in development of organic and inorganic materials using control of supersaturation level, control of nucleation temperature, solvent screening, heating and sublimation of the materials, low temperature and high temperature evaporation, rotovapor fast evaporation, seeding technology, capillary crystallization, introduction of additives, polymer-induced hetero-nucleation, nucleation confined in nanopores, heteronucleation on substrates such as ionic liquids and gels, laser-induced nucleation. Further extension of my research will be in multi-component systems such as salts, cocrystals and eutectic compositions because they were used as alternative methods to polymorphs in addressing the physico-chemical challenges of low aqueous soluble drugs with low bioavailability. In the same direction, Salts are well known in this field to make alternate formulation dosage forms and recently cocrystals have been developed in research labs, but eutectic compositions are not well explored in this regard. Therefore, I would like to take a important stand in this research field from crystal engineering strategies to their application in pharmaceutical formulation.

Potential applications of the Research Activity The model compounds and drugs studied in my PhD thesis work belong to the broad category of drug classification such as sulfonamides, amphoteric compounds, amino acids, antifungal azole drugs, sulfonylureas, fibrates and fenamates and hence there is a need to explore the same structure-property relationship for these many numbers of drugs in each of these categories. The idea

of expanding the study of polymorph screening and crystal engineering strategies to the other drugs in the same category using different crystallization conditions would provide interesting directions to solve the pharmaceutical and developmental challenges in drug industries.

Instruments Handled 1.

Trained in organic synthesis, separation, purification and characterization of organic molecules using TLC and column chromatography and various spectroscopic techniques like FT-IR, Raman, NIR, 1H-NMR, 13C-NMR.

2.

Analysis of different crystal forms (polymorphs, solvates, hydrates, salts and cocrystals) by X-ray diffraction (both single crystal XRD and Powder XRD) and Differential Scanning Calorimetry (DSC), Thermal Gravimetric Analysis (TGA), Hot Stage Microscopy (HSM), and FT-IR, NIR, Raman spectroscopy and ss-NMR spectroscopy.

3.

Hands-on experience with SMART APEX CCD X-ray diffractometer, Xcalibur Gemini Eos CCD X-ray diffractometer, crystal structure solution and refinement, determination, Bruker 400 MHz NMR spectrometer, Thermo Nicolet 6700 FT-IR and Raman spectrometer, Thermo Scientific Evolution 300 UV-VIS Spectrometer, Metler Toledo DSC/TGA instruments, Wagner Munz Hot stage microscope, Electrolab Dissolution Tester, Retsch MM 400 ball mill grinder.

4.

Sound knowledge of various softwares such as Polymorph Prediction CSD (CCDCCambridge Crystallographic Data Centre) for crystal structure database analysis, SAINT, SHELX-TL, CrysAlisPro 171.33.55, Olex2-1.0, WinGX, Platon for crystal structure solution and refinement, Mercury & XSeed for viewing and graphics, Powder Cell 2.4 for fingerprint match and quantification of polymorphic phases and least squares refinement, Crystal Explorer (Hirshfeld Surface Analysis) for analyzing intermolecular interactions and polymorphism

in

molecular

crystals,

XPac

to

compare

similar/dissimilar.

Extracurricular Skills 

CHEMDRAW, ISIS, PAGEMAKER, PHOTOSHOP and BIOX.



Science Awareness Exhibition, Demonstration and Participation.

crystal

structures

of

Declaration I hereby declare that whatever has been stated above is true to the best of my knowledge, correct and nothing material has been concealed there from.

Place: Tirunelveli Date:

2015

S. Sudalai Kumar

KANNAN MASANAM ASSISTANT PROFESSOR, DEPARTMENT OF CHEMISTRY, THIRUVALLUVAR COLLEGE, PAPANASAM, VICKRAMASINGAPURAM, TIRUNELVELI DISTRICT, TAMILNADU 627 425

Phone. 04634 220327, 221631 CELL: 07305094741

e-mail. [email protected]

DEGREE PhD M.Sc B.Sc

INSTITUTE Indian Institute of Technology Guwahati Madurai Kamaraj University St. Xavier’s College, Palayamkottai

CGPA/% 9.5 73.35 85.50

YEARS 2010-present 2007-2009 2004-2007

HSC

THE M.D.T. H.C. Hr. Sec. School,

73.91

2003

SSLC

Schaffter Hr. Sec. School,

83.40

2001

PROJECTS PhD “Synthesis of Chiral Soluble Macromolecular Catalyst and Their Application for Carbon-Carbon and Carbon-Heteroatom Bond Formation”

July 2010-Present

Prof. T. Punniyamurthy

Project Assistant “Development of Novel Oxidative Desulfurization process for

April 2010-July 2010

removing sulfur from Diesel”

Prof. T. Punniyamurthy

M.Sc “Decomposition of Peroxomonosulphate in the presence of Nickel(II) Oxalate”

June 2008-April 2009

Prof. M. S. Ramachandran

PUBLICATIONS 

T. Punniyamurthy and M. Kannan, “Polyaniline” e-EROS Encyclopedia of Reagents for Organic Synthesis, 2012.



M. Kannan and T. Punniyamurthy, “Effect of Ligand N,N-Substituents on the Reactivity of Chiral Copper(II) Salalen, Salan and Salalan Complexes Towards Asymmetric Nitroaldol Reaction” Tetrahedron:Asymmetry, 2014, 25, 1331.



G. Bharathiraja, M.Sengoden, M. Kannan and T. Punniyamurthy, “Expedient Synthesis of Tetrasubstituted Pyrroles via Copper-Catalyzed Cascade Inter-/Intramolecular Cyclization of 1,3-Enynes Carry a Nitro Group with Amines” Org. Biomol. Chem. 2015, 13, 2786.

BOOK PUBLICATIONS 

M. Kannan, M. Sengoden and T. Punniyamurthy, "Transition-Metal-Mediated Carbon-Heteroatom Cross-Coupling. An Overview" in Arene Chemistry: Reaction Mechanisms and Methods for Aromatic Compounds (Book Chapter) Ed: J. Mortier, Wiley, 2015.

CONFERENCES & SEMINARS  

Organised one day state level workshop on “First Aid Management”, January, 2016. Participated and presented a poster in the Frontiers in Chemical Sciences 2014 in Guwahati, December 04-06. DNS server 208.67.220.220

ACHIEVEMENTS    

SIR-NET, JRF Qualified on 21/12/2008 Qualified GATE 2009 (94.25 percentile) Certificate of merit First in B.Sc Chemistry. Prof. C. Srinivasan endowment gold medal for physical chemistry in M.Sc Chemistry.

TECHNICAL PROFICIENCY 

Handling as well as analytical knowledge in UV-Visible, IR, NMR and GPC



Independently able to operate and maintain Chiral Columns and Chiral HPLC



Analytical Knowledge in Mass and EPR

EXTRA CURRICULARS 

Co-ordinator “Health Club” Thiruvalluvar College, Papanasam

2015-Present



Co-ordinator “Youth Red Cross Society” Thiruvalluvar College Papanasam

2016-Present



Secured NCC ‘B’ certificate

(References available on request)

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