3/5/2016 U. Sailaja et al, Eur. J. Pharm. SCI 49 20131.

Slides:



Advertisements
Similar presentations
ILCC Edinburgh, July 2002 VAN DER WAALS INTERACTION AND STABILITY OF MULTILAYERED LIQUID-CRYSTALLINE SYSTEMS dr. Andreja [ arlah Univerza v Ljubljani.
Advertisements

Solutions n Solution – a homogeneous mixture of pure substances n The SOLVENT is the medium in which the SOLUTES are dissolved. (The solvent is usually.
Chapter 11 Liquids and Intermolecular Forces
Dielectric Relaxation processes at temperatures above glass transition
I. Kinetic Molecular Theory KMT
Intermolecular Forces and
DIELECTRIC PROPERTIES OF ION - CONDUCTING MATERIALS F. Kremer Coauthors: J. Rume, A. Serghei,
I. Characteristics of solutions a. Mixtures and solutions i. Mixtures are either heterogeneous or homogeneous. 1. Heterogeneous mixtures have non-uniform.
1 Relaxation and Transport in Glass-Forming Liquids Motivation (longish) Democratic motion Conclusions G. Appignanesi, J.A. Rodríguez Fries, R.A. Montani.
Workshop on Amorphous Solids, Hong Kong, September 2008 Lecture 1: Introduction to glasses Itamar Procaccia Institute of Theoretical Physics Chinese University.
LIQUIDS AND SOLIDS. LIQUIDS: Why are they the least common state of matter? 1. Liquids and K.M.T.  Are particles in constant motion? Spacing? Kinetic.
7. OTHER FAMILIES OF GLASSES AND DISORDERED CRYSTALS: PLASTIC CRYSTALS AND ORIENTATIONALLY DISORDERED CRYSTALS Comparative study of translational and orientational.
Investigation of Ionic Liquids by Positron Annihilation Lifetime Spectroscopy G. Dlubek 1†, Yang. Yu 2, R. Krause-Rehberg 2, W. Beichel 3 and I. Krossing.
Liquids and Solids.
Chapter 10 Liquids & Solids
Chapter 11 Liquids and Intermolecular Forces
Chapter 14: Liquids and Solids
Dielectric spectroscopy of glass-forming liquids under high pressure Marian Paluch Institute of Physics Silesian University Katowice, POLAND.
Lecture 19 Solids. Solutions. Crystals van der Waals forces Solvents and Solubles.
Intermolecular Forces Chapter 11 Intermolecular Forces, Liquids, and Solids John D. Bookstaver St. Charles Community College St. Peters, MO  2006, Prentice.
Intermolecular Forces and
Phases of Matter.
Shai Carmi Bar-Ilan, BU Together with: Shlomo Havlin, Chaoming Song, Kun Wang, and Hernan Makse.
Condensed States of Matter
Chapter 11. A substances state of matter depends on two things: The average kinetic energy of the particles (temperature) The strength of the intermolecular.
Liquids and Solids and Intermolecular Forces Chapter 11.
Chapter 11 Liquids and Intermolecular Forces
The Kinetic-Molecular Theory of Gases
Marian Paluch Co-workers: Ż. Wojnarowska K. Grzybowska A. Grzybowski K. Kamiński K. Adrjanowicz P. Włodarczyk J. Pionteck (Christian-Albrechts University.
Intermolecular Forces, Liquids, and Solids Chapter 11 Brown-LeMay.
CHEMISTRY ANALYTICAL CHEMISTRY Fall Lecture 13.
Relaxation dynamics of water in the aqueous mixtures of propylene glycol oligomers at ambient and elevated pressure 6 th International Discussion Meeting.
K. Adrjanowicz, Z. Wojnarowska, P. Wlodarczyk, K. Grzybowska, K. Kaminski, M. Paluch K. Grzybowska, K. Kaminski, M. Paluch Institute of Physics, University.
1 Lecture 14 Dielectric Spectroscopy of Glass forming systems. n-Alcohols Glycerol Polymers.
Liquids & Solids. Objectives 12-1 describe the motion of particles of a liquid and the properties of a liquid using KMT define and discuss vaporization.
Intermolecular Forces. Forces that hold solids and liquids together may be ionic or covalent bonding or they may involve a weaker interaction called intermolecular.
Solution properties Definitions –Solution –Solvent –Solute –Solubility –Saturated solution Concentration expression Matter – Solid, liquid, gas Vapor.
1 SHIMIZU Group ONODA Suzue Metallization and molecular dissociation of SnI 4 under pressure Ref: A.L. Chen, P.Y. Yu, M.P. Pasternak, Phys. Rev. B. 44,
N 10 pg List major types of intermolecular forces in order of increasing strength. Is there some overlap in.
T.T. and D.R.  In a liquid, molecules can slide over and around each other.
Chap 12 Liquids and Solids. Properties of Liquids and the Kinetic-Molecular Theory Liquid- is a form of matter that has a definite volume and takes the.
Properties of ionic compounds Standard chem Objectives 7 Properties of ionic compounds and relation to the ionic bond.
© 2015 Pearson Education, Inc. Chapter 11 Liquids and Intermolecular Forces James F. Kirby Quinnipiac University Hamden, CT Lecture Presentation.
Condensed States of Matter: Liquids and Solids Chapter 14
Marco G. Mazza Departmental Seminar Boston – February Acknowledgements: Kevin Stokely, BU Elena G. Strekalova, BU Giancarlo Franzese, Universitat.
Physical Behavior of Matter Review. Matter is classified as a substance or a mixture of substances.
An investigation into the stability and solubility of amorphous solid dispersion of BCS class II drugs Shrawan Baghel, WIT.
The behavior of gases in motion is described by the kinetic molecular theory. Kinetic molecular theory:  gases are small particles, separated by empty.
CHAPTER 14: LIQUIDS AND SOLIDS.  Condensed State- substances in these states have much higher densities than they do in the gaseous state CONDENSED.
DO NOW IN M.C. PACKET MATTER QUESTIONS AIM: REGENTS REVIEW TOPIC 4 – MATTER.
Kintetic Molecular Theory
Study of Dielectric Properties of SBN Ceramics
Melting Point Dr. Zerong Wang at UHCL.
Kintetic Molecular Theory
11.3 Some Properties of Liquids
12 Chemistry Atomic Structure and Bonding CR 07
Physical Behavior of Matter Review
Kintetic Molecular Theory
12.2 – NOTES Solutions Intro
Adapted from Chapter 11 Intermolecular Forces; Liquids, and Solids
* 07/16/96 SOLUTIONS *.
Intermolecular forces
Gases, Liquids and Solids
Solid state Chemistry (CHEM 422)
Chapter 11 Liquids and Intermolecular Forces
Liquids and Solids Chapter 13.
Intermolecular forces
Intermolecular Forces and
Unit 2 B Matter, Energy, and Changes
Presentation On INFRARED SPECTROSCOPY
Presentation transcript:

3/5/2016 U. Sailaja et al, Eur. J. Pharm. SCI

Dr. Sailaja U Department of Physics, M.E.S. Keveeyam College. Valanchery, Malppuram, Kerala, India. Relaxation dynamics of amorphous pharmaceuticals

3/5/2016 U. Sailaja- Indoglobal Health care 2015 Motivation Drug administration is better in the amorphous state than in the crystalline state. But shelf-life of the amorphous drugs are low because there is a greater chance for crystallization due to the molecular mobility present in the amorphous state. Aim Objective To investigate different relaxation processes (dielectric properties) present in glass-forming pharmaceuticals by BDS. To investigate different relaxation processes present in the amorphous pharmaceuticals and their role in the crystallization of drugs. Apply this to design amorphous drugs having better solubility, bioavailability and longer shelf-life.

3/5/2016 U. Sailaja et al, Eur. J. Pharm. SCI

3/5/20165

API are classified accordingly Amorphous pharmaceuticals IIIIIIIV solubilityhigh low permeabilityhighlowhighlow amorphous route can give improved solubility for water insoluble solid APIs

mixing of solid API in the oral route Amorphous pharmaceuticals mixing – escape of individual molecule from the Madelung bond of crystalline API. Getting energy to overcome this barrier from thermal fluctuations is less probable. amorphous state –only very weak van der Waal’ s interaction. molecules are at higher free energy. Hence can mix better and quicker

Vitrification of solid API cooling faster can bypass this ordering to retain disorder and reach glassy state glass specific heat

amorphous API can gradually transform to crystalline phase Vitrification of API – issues to be addressed 100 s & above 100 s – and lower Glass supercooled liquid liquid

amorphous API can gradually transform to crystalline phase Vitrification of API – issues to be addressed shelf-life needed is more than 2 years stability of API against degradation is yet to be systematically investigated. systematic investigation is needed for taking this to application front.

3/5/2016 U. Sailaja et al, EUR. J. Pharm. SCI

3/5/2016 U. Sailaja et al, EUR. J. Pharm. SCI Theory: The polarization studied by dielectric spectroscopy is the orientational polarizability which is due to dipole relaxation. The important function that is measured from dielectric spectroscopy is the complex dielectric function ε * ( ω )= ε ′ ( ω )-i ε ′′ ( ω ) ( ε ′ -real part, ε ′′ -imaginary or loss part).

Broadband dielectric spectrometer Novocontrol ( Hz)

Data analysis The analysis time was 18 hours in BDS Frequency range is between to 10 7 Hz Temperature range is from -150 to 100 degree The spectra is analyzed by using Win-fit software Frequency corresponding to maximum dielectric loss in alpha process can be represented in Arrhenius diagram VFT Fit is done for alpha process to calculate Tg and fragility(m) and T 0

Ketoprofen Dielectric loss curves obtained for ketoprofen during heating U. Sailaja et al, Eur. J. Pharm.Sci, 49 (2013) 15 From K (18degree) onwards the dielectric strength of α-process starts decreasing shows tendency for crystallization of ketoprofen. ( Orudis/Oruvail)

HN fitted curves 3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci Fenofibrate Primary relaxation above T g Secondary relaxation below T g.

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci HN fitted Spectra of Fenofibrate

Master plot of ketoprofen formed by shifting several spectra near T g to overlap the spectrum at K 3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci Tramadol monohydrate (Kaminski 2010) Glibenclamide (Wojnarowska 2010)

Relaxation map of ketoprofen T 0 = 222K (Hancock1997) 3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci Yu et al., 2001, pointed out that if m 75 the liquids belongs to fragile group

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci Relaxation map of Fenofibrate

Strong and fragile glasses Strong systems: Strong resistance against structural degradation Fragile systems: Shows large deviation from Arrhenius law VFT equation R. Boehmer et al 1993 =τ VF exp[B/(T—T 0 )] m=16, 200 Angell, C.A. 1991

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci

3/5/2016 U. Sailaja IGHC Dielectric studies: Molecular mobility is found to be responsible for the crystallization of the APIs and JG relaxation is one of the main reasons for devitrification and found to universal. To prevent devitrification of the drugs we have to understand the complete factors responsible for devtrification so that the drugs can attain maximum shelf-life in the amorphous form. Binary mixture of these APIs with different excipients can be done to check the miscibility of the drugs and thereby avoiding crystallization during processing, handling and storage in the amorphous phase for getting maximum shelf-life and stability.

References [1] Tripathi KD (MD) Essentials of Medical Pharmacology [2] Alie J,Menegotto J, Cardon P, Dupla H, Caron A, Lacabanne C, Bauer M. J.Pharm.sci 93: (2003) [3] Boehmer R, Ngai KL, Angel CA, Plazek DJ. J. Chem. Phys 99: (1993) [4] B.C. Hancock, G. Zografi. J.Pharm.sci. 7 (1997) [5] Angell, C.A. Relaxation in liquids, polymers andplastic crystals -strong/fragile patterns and problems. J. Non-Cryst. Solids. 1991, ,

3/5/2016 U. Sailaja IGHC  Dr. Shahn Thayyil, University of Calicut, India  Dr. G. Govindaraj & Mr. Krishnakumar, Pondicherry University  Dr. Jayanthi, Sr. Scientist, CMPR, AVS, Kottakkal, Kerala, India  Mr. Mohit Aggarwal, IIT Powai, Mumbai, India  Mr. A. Arun Sr. Manager, Product development, AVS, Kottakkal  Dr. Ashok Aggarwal, NIPER, Mohali, Punjab, India  Cochin University, India  To MES management, Principal, and all members  of MES Keveeyam College, Kerala, India Acknowledgments

3/5/2016 U. Sailaja et al, Eur. J. Pharm.Sci