1. THERMAL ANALYSIS FOR PREFORMULATION TRIALS
LIAKAT CHOWDHURY
M.PHARM(1ST YEAR)
DEPARTMENT OF PHARMACEUTICS
GUPTA COLLEGE OF TECHNOLOGICAL SCIENCES
ASANSOL

2. PREFORMULATION
Preformulation is the first step of rational development of a dosage form of a drug substance
It include investigation of physico -chemical property of new drug substance that could affect drug performance and development of efficacious dosage form
It relates the pharmaceutical & analytical investigation to that proceed & support to develop a dosage form

3. GOALS OF PREFORMULATION
To establish necessary physico -chemical parameters of new drug substance.
To determine the kinetic rate profile.
To establish physical characteristics of drug substance.
To establish compatibility with common excipients.

4. Thermal Analysis Techniques
IUPAC definition - a group of techniques in which a physical property is measured as a function of temperature, while the sample is subjected to a controlled temperature programme (heating, cooling or isothermal).
A range of techniques e.g.:
Differential Thermal Analysis (DTA) – temperature
Differential Scanning Calorimetry (DSC) – energy
Thermogravimetric Analysis (TGA) – mass
Thermomechanical Analysis (TMA) – dimensions
Dielectric Analysis (DEA) – dielectric/electric properties

5. Basic Principles of Thermal Analysis
Modern instrumentation used for thermal analysis usually consists of the following parts:
sample holder/compartment for the sample
sensors to detect/measure a property of the sample and the temperature
an enclosure within which the experimental parameters (temperature, speed, environment) may be controlled
a computer to control data collection and processing
sample
sensors PC
temperature
control (furnace)

6. ROLE OF THERMAL ANALYTICAL METHODS IN PREFORMULATION STUDY
These are unique methods in the field of polymer analysis & of high value for a solid state analysis.
They finds wide application in
Detection of impurity
Determination of moisture content in any drug substance or any excipient
Study of polymorphism
Characterization of hydrates & solvates
Degree of Crystallinity
Study of phase diagram
Drug excipient compatibility study
Study of complexation

7. Differential thermal analysis (DTA)
DTA involves heating or cooling a test sample and an inert reference under identical conditions, while recording any temperature difference between the sample and reference.
This differential temperature is then plotted against time, or against temperature.
Changes in the sample which lead to the absorption or evolution of heat can be detected relative to the inert reference.

8. Differential Scanning Calorimetry
Differential Scanning Calorimetry (DSC) is one of the most frequently used techniques in the field of thermal characterization of solids and liquids
Pharmaceutically Relevant Information Derived from DSC Analysis -
melting/crystallization behavior
solid-solid reactions
polymorphism
degree of crystallinity
glass transitions
cross-linking reactions
oxidative stability
decomposition behavior
purity determination
specific heat

9. Differential Scanning Calorimetry – Principle of Operation
a sample is placed inside a crucible which is then placed inside the measurement cell (furnace) of the DSC system along with a reference pan which is normally empty (inert gas may be used).
By applying a controlled temperature program (isothermal, heating or cooling at constant rates), phase changes can be characterized and/or the specific heat of a material can be determined.
Heat flow quantities are calculated based on calibrated heat flow characteristics of the cell.

10. Thermogravimetric Analysis (TGA)
A technique measuring the variation in mass of a sample undergoing temperature scanning in a controlled atmosphere.
Thermobalance allows for monitoring sample weight as a function of temperature.
The sample hangs from the balance inside the furnace and the balance is thermally isolated from the furnace.
balance
sample
purge gas
furnace

11. Summary of Pharmaceutically Relevant Information Derived from TGA Analysis
Moisture and Volatiles Content of Materials
Composition of Multicomponent Systems
Thermal Stability of Materials
Oxidative Stability of Materials
Estimated Lifetime of a Product
Decomposition Kinetics of Materials
The Effect of Reactive or Corrosive Atmospheres on Materials
Quantitate the presence of solvated species within a bulk drug sample.

12. Limitation of Thermal Analysis
Low sensitivity of transitions involving small energies.
Impurity consisting of molecules of same size, shape , character as those of the major component are not detected by DSC.
TGA used to study hudrates and moisture study are not always reliable.
Thermal analysis are affected by number of factors.

13. THANK YOU