DTA & DSC

Differential thermal analysis & differential scanning calorimetry : 

Differential thermal analysis & differential scanning calorimetry 1 A seminar on Presented By Mr. Ashutosh P andya 1 st semester (2010-2011) M.Pharm. [QUALITY ASSURANCE] Roll No. 18 Guided By Dr. N.J Shah M.Pharm; Ph.D. Principal Department Of Pharmaceutical Chemistry

CONTENTS: 

CONTENTS Principle :- Factors:- Instrumentation:- Applications:-

INTRODUCTION: 

INTRODUCTION In differential thermal analysis (DTA) both the test sample and an inert reference material (usually α-alumina) undergo a controlled heating or cooling programme which is usually linear with respect to time. There is a zero temperature difference between sample and reference material when the formal dose not undergo any chemical or physical change. If, however any reaction takes place, then a temperature difference ∆T will occurs between the sample and the reference material.

Slide 4: 

Hence in endothermic change e.g. when the sample melts or is dehydrated, the sample temperature is lower than that of the reference material. This condition is only transitory because on completion of the reaction the sample will again show zero temperature difference compared with the reference. In DTA a plot is made of ∆T against temperature or time, if the heating or cooling programe is linear with respect to time an idealized DTA curve is shown in figure:-

Slide 5: 

As shown in figure (1) is an exothermic peak and (2) endothermic peak. Both the shape and size of the peak can give a large amount of information about the nature of the test sample. Hence sharp endothermic peaks often signify changes in crytallinity or fusion process, whereas broad endothermic arise from dehydration reactions. Physical changes usually results in endothermic curves while chemical reactions, particularly those of an oxidative nature, are predominantly exothermic.

Slide 6: 

Differential scanning calorimetry ( DSC) measures the deferential energy required to keep both the sample and reference chemicals at the same temperature. Hence when an endothermic transition occurs, the energy absorb by the sample is compensated by an increase energy input to the sample in order to maintaine a zero temperature difference. The DSC curve is recorded with the chart abscissa indicating transition temperature and peak area measures the total energy transfer to the sample.

FACTORS AFFECTING THE DTA CURVE: 

FACTORS AFFECTING THE DTA CURVE Environmental factors Instrumental factors Sample factors

ENVIRONMENTAL FACTORS: 

ENVIRONMENTAL FACTORS The DTA technique is more sensitive to gaseous environment around the sample. Further, reaction with gaseous atmosphere with sample may also produce extra peak in the curve for e.g. oxygen in air which causes an oxidation reaction may cause rise to an exothermic peak. Two types of gaseous atoms used. Static gaseous atom A dynamic gaseous atom

Slide 9: 

A static gaseous atmosphere is difficult to reproduce because the atom surrounding the sample is changing in concentration, chemically due to evolved gases and physically due to convection current. Therefore, studies in static are imprecise. Results obtained in dynamic atoms where the gases are swept past the sample in a controlled way are reliable and reproducible. The sweep gases can be either inert or reactive.

INSTREUMENTAL FACTORS: 

INSTREUMENTAL FACTORS Sample holder Deferential temperature sensing devices Furnace characteristic Temperature programme controller Thermal regime

Sample holder: 

Sample holder If the sample holders are made from materials of high thermal conductivity (e.g. metals) sharp exothermic peaks but relatively flat endothermic peaks are obtained. However, the reverse is true if the sample holders are fabricated from materials of poor thermal conductivity. (e.g. ceramic) The nature of material may not only change the shape of the peak but may change the inception and peak temperature. For better resolution, the size of the holders and the amount of the sample should be as small as possible.

Differential temperature sensing device: 

Differential temperature sensing device If the wire used in temperature sensing devices is much thick, more distortion of the peak heights and peak temperature may takes place. However, if thinner wires are used, lesser distortion in peak height and peak temperature may takes place. But the resistance of thinner wire is much higher and may be unsuitable.

Furnace characteristic: 

Furnace characteristic The type of winding shows a direct effect on the DTA curve. If the winding used in furnace is not uniform, the base line is changed one should prefer grooved muffle cores because it ensures uniformity in winding.

Temperature Programme Controller: 

Temperature Programme Controller One should be quite careful while selecting the temperature programme controller because a constant heating rate is required in DTA. If one employs the switching off or on of full power, considerable noise may occur particularly at temperature above 700˚c. Therefore, on-off type controllers are not used. Generally, one must use a motor driven various in conjugation with a proportional position adjusting type programme controller.

Thermal regime: 

Thermal regime The heating rate has a great influence on DTA curves. Higher the heating rates, higher the peak temperature and sharper the peaks with greater intensity generally heating rates of 10 to 20˚ per min. are employed.

SAMPLE CHARACTERISTICS: 

SAMPLE CHARACTERISTICS Physical Characteristics: particle size alters the peak area particle size also influences the peak temperature generally with increased in particle size, the peak temperature is shifted to higher value. Particle size also alters the completion temperature generally the completion temperature decrease with the decreasing particle size. Besides the particle size, the weight of sample also affects. The weight of sample also influences the peak intensity and temperature.

FACTORS EFFECTING DSC CURVES: 

FACTORS EFFECTING DSC CURVES Sample shape:- The shape of the sample has little effect on the quantitative aspects of DSC but has more effect on qualitative aspects. However, sample in the form of a disc film or powdered spread on the pan are preferred.

Sample Size: 

Sample Size About 0.5 to 10 mg is usually sufficient. Smaller samples enables faster scanning, give better shape peaks with good resolution and provide better contact with the gaseous environment.

The basic instrument consists of: 

The basic instrument consists of A sample and reference holder assembly Furnace control A reaction chamber allowing analysis in a variety of atmospheric system A suitable sensor to measure the temperature difference between the sample and reference material An amplifier for ∆T A suitable chart recorder

Slide 21: 

Two small metal platforms, (1)& (2) are each welded to a chrome- alumel thermo coupling, (3) & (4) the platforms are mounted in the base of a hollow metal cup (5), the walls of which are wound externally with the specially insulted heater (6). The metal disc (7) is above the base of the cylindrical cup through which the thermo couple assemblies produce. The gas inlet (8) to the sample chamber (9) is via a small capillary tube (10)

Slide 22: 

The heater assembly is fitted with a tight fitting metal lid which nay incorporated either a Pyrex window or be fitted with a small capillary with one end in position over the sample platform. The total volume of the sample chamber is about 5 cm 3 . Sample containers used with this instruments are dish shaped and are usually made of either aluminum or platinum .

SAMPLE HOLDER: 

SAMPLE HOLDER Materials metallic as well as non metallic materials are employed for the fabrication of the sample holders. Metallic materials generally include nickel, stainless steel, platinum and its alloys. Non metallic materials generally include glass or sintered alumina. Metallic holders give rise to sharp exotherms and flat endotherms .

Geometry: 

Geometry The nature of physical contact between the sample, thermo couple junction and the specimen holder affect the DTA signals the best situation is one when a thermo couple junction is kept in the sample but the fear of the chemical attacks isolates the thermo couple from the sample. In order to prevent chemical attack by the sample, the thermo couple junction is coupled with the metallic sheath or one may use a suitable design of the specimen holder.

FURNACE: 

FURNACE In DTA apparatus, one always prefer a tubular furnace. This is constructed with an appropriate material wound on a refractory tube. Such furnaces possess the desired characteristic for good temperature regulation and programming this are fairly inexpensive.

TEMPERATURE CONTROLLER AND RECORDER: 

TEMPERATURE CONTROLLER AND RECORDER Temperature control: In order to control temperature the three basic elements are required. These are sensors, control elements and heater. There are two methods for controlling temperature, these are as follows:- On-off control Proportional control

THERMOCOUPLES: 

THERMOCOUPLES Thermo couples made from channel P and alumel wires are used to measure and control temperature upto 1100˚c in air. Above 1100˚c, one should used thermo couple made from pure platinum and platinum-rhodium alloy wires.

COOLING DEVICES: 

COOLING DEVICES The cooling system is considered separate from the temperature programmer because in most instrument cooling is completely independent from heating.

APPLICATIONS FOR DTA & DSC: 

APPLICATIONS FOR DTA & DSC By DTA, one can study physical transformation like melting, freezing, volatilization, change in crystalinity and specific heat, adsorption, and desorption as well as chemical changes. For raw materials (drugs/ excipients ) Study of polymorphism:- (crystalline modification) melting, sublimation, kinetics, stability, solubility, dissolution rate etc. (for sorbitol , mannitol , glyceride , TiO 2 ) Study of pseudo polymorphism- hygroscopicity )

Slide 30: 

Purity determination (from melting point depression) X=mole fraction of impurities ∆T=melting point depression ∆ H f =molar enthalpy of fusion of pure raw materials R= gas constant (8.314 J/mol/K) T 0 = melting point of pure raw material

Slide 31: 

Stability screening Pre formulation studies (drug- excipient interaction) Control of processing : tableting , spray drying, suspensions) Physical changes of excipients during storage of dosage form. For e.g. anhydrous lactose monohydrate

Slide 32: 

Analysis of dosage form-quantification Triamcinolol -A & B polymorphs Ampicillin trihydrate -polymorphs Testosterone purity Identification of substances. We know that the DTA curves for two substances are not identical therefor these serves as finger print for various substaces . Identification of products when a substance reacts with another substance the product are identified by their specific DTA curves.

Comparison of DTA & DSC Techniques: 

Comparison of DTA & DSC Techniques Sr No Aspect DSC DTA 1 Size of sample 2 TO 10 mg 50 TO 200mg 2 Sensitivity of measurement A few J/mole 0.5 K.J/Mol 3 Heating &cooling cycles Programmed Heating And Cooling Possible Generally program heating 4 Second order phase transition 200mg Not observed 5 Specific heat measurement Accurate Not accurate