- Introduction to thermal analysis, Techniques and applications. (Michael E. Brown).pdf - Ebook download as PDF File .pdf) or read book online. 1. INTRODUCTION. The International Confederation of Thermal Analysis and Calorimetry  defines “Thermal Analysis” as a set of techniques. Introduction to Thermal Analysis: Techniques and Applications DOWNLOAD PDF Thermal Analysis: Fundamentals and Applications to Polymer Science.
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Introduction to. Thermal Analysis. Techniques and Applications. Second Edition. Michael E. Brown. Kluwer Academic Publishers. Introduction to Thermal Analysis. Techniques and Applications. Edited by. Michael E. Brown. Chemistry Department,. Rhodes University,. Grahamstown, South. to Thermal Analysis Techniques and Applications Edited by Michael E. Brown DRM-free; Included format: PDF; ebooks can be used on all reading devices.
Differential thermal analysis or DTA is a thermoanalytic technique that is similar to differential scanning calorimetry. In DTA, the material under study and an inert reference are made to undergo identical thermal cycles, i. Changes in the sample, either exothermic or endothermic, can be detected relative to the inert reference. Thus, a DTA curve provides data on the transformations that have occurred, such as glass transitions, crystallization, melting and sublimation. The area under a DTA peak is the enthalpy change and is not affected by the heat capacity of the sample. A DTA consists of a sample holder, thermocouples, sample containers and a ceramic or metallic block; a furnace; a temperature programmer; and a recording system.
An alteration in the temperature of The operating conditions: nitrogen flow rate: melting peak of metformin in all proportions was 50 mL min—1 heating rate: 10 K min—1 up to K. The melting process of metformin is not Aluminium sample pans and about 2. Temperature and calorimetric calibration was done using indium and zinc standards. Results and discussion Differential thermal analysis DTA curves of metformin and its binary mixtures showed that the drug melts at K, the corresponding heat effect is — J g—1 is in agreement with the literature data .
DTA curves of the binaries show that except of the metformin—lactose and metformin—starch mixtures, the melting peak temperatures did not change remarkably data in Table 1. Data were confirmed more precisely by phase diagram studies using DSC.
End decomp. Figure 2b shows a displacement in the melting Thermogravimetric studies of MET and its binary temperature of metformin in all proportions of the mixtures with different excipients showed different MET—Starch mixtures confirming the fact of interaction thermal behaviour with regard to the number of mass between the two compounds. One possible reason of loss stages data in Table 2. Starch presents a great variety with regard to its chemical composition amylose and amylopectin.
Besides, this is a natural polymer and can be originated from different regions. Consequently, for its application in the pharmaceutical industry a better quality control is necessary . The calculated data evidenced a References first order of kinetic behavior for MET with Ea value: Amini, A.
Ahmadiani and P. Gazerani, J. Balestrieri, A. Magri, A. Magri, D. Marini and A. Sacchini, Thermochim. While numerous techniques are available, the primary differences in the techniques are the properties of the material being studied as listed in Table 1. Admittedly, as the needs of the researcher change and new materials are identified in formulation development, less commonly used techniques are being utilized and developed resulting in a very dynamic and exciting field of research.
This review will be presented in two major sections.
The first will be thermal analytical methods commonly used in the pharmaceutical sciences, primarily DSC including several specialized techniques and TGA. The second will focus on applications in the pharmaceutical sciences including solid-state characterization of polymorphism, solid dispersions and polymeric dosage forms.
These instruments are available from several manufacturers in a wide range of price and applications. The basic difference between the two techniques is that DTA measures a difference in temperature whereas DSC, in theory allows for the measurement of a change in enthalpy.
Classical DTA measures the difference in temperature between the sample and reference which undergoes no phase changes as the furnace goes through a computer controlled temperature program.
The temperatures of both the sample and reference material increase or decrease uniformly until the sample reaches a point that it undergoes a phase change, which is either endothermic or exothermic and the difference in temperature is recorded. Although useful information is gained using DTA, there are several drawbacks to the technique which result in making it difficult to quantify the results and obtain information regarding the enthalpy of the sample transitions .
These difficulties were overcome with the development of DSC.
Two basic types of DSC instruments are commercially available today. While employing different techniques to obtain the measurement, both types of instruments measure heat flow and this seem to qualify as DSC under the ICTAC definition. Another important difference that should be pointed out is that at this time there is no common convention as to how DSC results should be presented.
Depending on the instrument used, the default settings may be to report endothermic events in the upward direction or downward with exothermic events in the opposite direction.
Today it is commonly referred to as a DSC method.
This development was an improvement over DTA in that it allowed for a measurement in the changes in heat flow as opposed to temperature only. This was accomplished by the addition of a second series of thermocouples to measure temperatures of the furnace and a heat sensitive plate.
During a phase change, the heat emitted or absorbed by the sample would alter the heat flux through the heat sensitive plate. By measuring the heat capacity of the heat sensitive plate as a function of temperature during the manufacturing process, an estimate of the enthalpy of transition can be made from the incremental temperature fluctuations . As the name implies, pc-DSC measures the change in energy or power necessary to maintain the sample and references material at the same temperature throughout the heating or cooling cycle.
This is accomplished through a different instrument design than that commonly found in hf-DSC instruments. With pc-DSC, two individual heaters are used to control the heat flow to the sample and reference holders. Individual resistance sensors are placed within each holder and measure the temperature at the base of each.
When a phase change occurs and a temperature difference is detected between the sample and reference, energy is supplied or removed until the temperature difference is below the threshold previously mentioned. Energy input as a function of temperature or time is then recorded which is proportional to the heat capacity of the sample .
From Reference 4 Regardless of the type of instrument used researchers will find that DSC offers a plethora of information regarding phase changes of materials. All DSC instruments operate over a wide temperature range both isothermally and dynamically and can be used for solids, semi-solids and liquids.
A typical DSC thermogram is shown in figure 1. Although DSC results reveal temperatures or temperature ranges, at which endothermic or exothermic events occur, interpretation of the results can be challenging.
Figure 2 presents several of the events which are typically measured with DSC. As noted in the figure, several events can be endothermic or exothermic but with a basic understanding of thermodynamics the researcher can begin to deduce which event is most likely. For example, both melting and evaporation are endothermic events.
However for most crystals especially when pure melting peaks are usually much sharper indicating a very small temperature range over which the transition occurs. Likewise, decomposition and oxidation are both broad exothermic peaks, but with the ability to control the atmosphere in which the experiment is conducted the difference can be determine. Crystallization and decomposition may both produce fairly sharp exothermic peaks on DSC but only the decomposition will be accompanied by decrease in mass on TGA in the same temperature range.
These results are typical of first- or second-order thermodynamic phase transitions, which are in an equilibrium state. Glass transitions, on the other hand, are neither first- nor second-order transitions since neither the glassy state nor the viscous state is an equilibrium state .
Typical DSC thermograms will reveal glass transitions as step-wise increases in the heat capacity Cp of the sample. This is due primarily to the increase in molecular motion of the sample above the Tg. In some cases, the determination of Tg is relatively straightforward but this work can be some of the most challenging done with DSC. Frequently a sample in which glass transitions need to be studied will contain material that is only partially amorphous or may be in complex mixtures of materials that are crystalline or amorphous.
Additionally the thermal history of an amorphous sample will greatly influence possible glass transitions. To overcome some of these challenges, manufacturers have developed software techniques that can in theory separate kinetically reversible and irreversible events, which allows the researcher to more clearly detect changes in the Cp. This is accomplished by applying a perturbation to the heating program of a conventional DSC followed by a deconvolution of the results by mathematical processes to separate the reversible and irreversible events.
In theory, changes in the Cp of the sample are considered reversible and most but not all changes in enthalpy can be identified by a change in heat flow considered irreversible. The separation or deconvolution of Cp and enthalpy signals is described in equation 1 below . While this can be accomplished with either pc- or hf-DSC instruments, recent improvements in the sensitivities and more accurate temperature control for both types of instruments have also contributed to making MT-DSC a valuable and accepted technique.
Thermogravimetric Analysis TGA or TG Thermogravimetric analysis is an experimental method whereby changes in mass are used to detect and measure the chemical or physical processes that occur upon heating a sample . Figure 2 represents common TGA results and demonstrates how they are commonly used in interpreting results from DSC analysis. Although several variations in the overall design exist, the simple design of TGA instruments includes a highly precise analytical balance to which the sample pan is attached.
The sample pan is typically suspended within a heater, which is under computer control. The control of the balance and sample atmospheres again varies but in basic instruments, they share a controlled atmosphere usually of nitrogen gas. Most instruments also have the ability to use isothermal or dynamic heating and cooling cycles and some can also be programmed to hold a specific temperature once a change in mass is detected then maintain that temperature until there is no further change and resume the heating program.
TGA results like DSC can vary greatly depending on sample and experimental conditions which can make it very difficult to compare the work of one researcher to another.
An excellent explanation of some of these challenges can be found in references [2,5]. In addition to supporting other thermal analysis techniques, TGA is extremely useful in studying various kinetic processes of solids and liquids as long as the processes involve the loss of mass.
Other common applications in the pharmaceutical sciences include the characterization of hydrates including the desolvation process and the determination of decomposition, vaporization or sublimation temperatures.
This may be a convenient and time saving feature and although quite accurate, the performance of each technique does suffer somewhat due to construction requirements.
Thermal Analysis Applications in the Pharmaceutical Sciences Although most thermal analysis methods can deal with samples as solids, semi-solids or liquids, a review of the current literature would suggest that the broad term, solid-state characterization, could apply to a majority of the applications in pharmaceutical research. Common applications include the characterization of the physicochemical properties of crystalline solids and the detection and identification of polymorphic forms.
With the increased utilization of solid dispersions and other polymeric dosage forms, thermal analytical techniques have been called upon more frequently to aid researchers with their development and characterization. Thermal analytical techniques are also used to study the effects of lyophilization and to develop optimal lyophilization formulations and cycles.
Several techniques are also used to study kinetics in the solid-state, including decomposition, accelerated stability and the effects of aging on various formulations. Polymorphism A crystalline solid may form polymorphs under common manufacturing conditions. Because the physicochemical properties of various polymorphs can vary greatly, identifying the possibility of polymorph formation is critical in product development.
DSC has proven to be very useful in the identification of polymorphic transitions primarily due to the ability to easily study the sample under various heating and cooling conditions needed to induce the polymorph formation [7,8,9,10].
Additionally once identified, DSC can be used to monitor samples for the development of polymorphs under various storage conditions or under various manufacturing conditions such as grinding, heating, and drying [11, 12].
Solid Dispersions and Polymeric Dosage Forms Efforts to formulate drugs with poor aqueous solubility and bioavailability have led to the increased utilization of solid dispersions. Solid dispersions consist of at least two solid components one being the matrix forming component the other being the drug.
The drug may be dispersed in the matrix as either crystals, amorphous clusters or uni-molecularly in what is commonly termed a solid solution. These dispersions may then be formulated into granules, beads, films, microspheres, tablets etc. Karavas, et. DSC revealed that partial miscibility was present between the two components which led to an optimal glass dispersion of the felodipine in the matrix and resulted in a significant enhancement of the dissolution and release kinetics of the felodipine.
Similarly, Mura, et. DSC was used to characterize and confirm the formation of the dispersions produced by various techniques and dissolution profiles were studied with standard methods. Solid dispersion formulations are also finding increased use in the development of transdermal formulations.
Cho, et. The dispersion, which was also studied by X-ray diffraction, was found to contain quinupramine in an amorphous state which led to enhanced drug release. DSC results showed that the pure drug existed in the crystalline state and remained in the crystalline state after a physical mixture with EVA was produced as evidenced by an endothermic peak corresponding to the melting point of pure drug. However after a , matrix of drug and EVA was formed by the casting method, no endothermic peak was observed suggesting drug was present in the amorphous state.
DSC methods were used to assess the miscibility of drug-polymer and polymer-polymer blends and to determine formulations most likely to produce solid solutions or dispersions upon extrusion. Additionally, samples could be analyzed post extrusion to confirm the solid solution or dispersion formation and periodically sampled form accelerated storage conditions to determine if drug was recrystallizing in the matrix.
Another important application was predicting optimal extrusion conditions while using the small sample sizes utilized in DSC.