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

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

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.

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

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)

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

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.

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

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.

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

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.

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.

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