Excipient thermal analyses

The sample temperature is increased in a linear fashion, while the property in question is evaluated on a continuous basis. These methods are used to characterize compound purity, polymorphism, solvation, degradation, and excipient compatibility [41], Thermal analysis methods are normally used to monitor endothermic processes (melting, boiling, sublimation, vaporization, desolvation, solid-solid phase transitions, and chemical degradation) as well as exothermic processes (crystallization and oxidative decomposition). Thermal methods can be extremely useful in preformulation studies, since the carefully planned studies can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [7]. 

M. Tomassetti, A. Catalan , V. Rossi, and S. Vecchio, Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms in some binary mixtures, J. Pharm. Biochem. Anal. 37 (2005), 949-955. 

In this era of automatic titrators, microprocessor-controlled thermal analysis, and definitive spectral techniques, one of the most powerful techniques, that is, optical microscopy, is frequently overlooked. The value of direct sample observation, preferably while it is exposed to different relative humidities, cannot be overstated. In the author s laboratory, a plexiglass chamber was constructed that can be placed on the stage of the microscope, through which air of known humidity can be circulated. This simple technique has been very useful in examining the swelling (or lack) of disintegrants and the influence of very hydrophilic excipients in combination with a moisture sensitive drug. ... 

A recent detailed review about thermal analysis of polymorphs and pseudopolymorphs listed more than 300 drug substances presenting this behavior in the literature. Polymorphism of excipients and their thermal analysis has been reviewed in Ref... 

The use of thermal analysis techniques for pharmaceuticals implies the knowledge of the thermal behavior of the excipients. A great number of publications deal with polymorphic behavior of excipients and especially with the amorphous forms as prerequisite knowledge for freeze drying and milling processes. 

Smith A. Use of thermal analysis in predicting drug-excipient interactions. Anal Proc 1982 ... 

M. L. Cotton, D. W. Wu, and E. B. Vadas, Drug-excipient interaction study of enalapril maleate using thermal analysis and scanning electron microscopy, Int. J. Pharm. 40, 129-142(1987). 

Thermal analysis is an extremely important analytical tool for the pharmaceutical industry. All transitions in materials involve the flow of heat (either into the sample during an endothermic event or out of the sample during an exothermic event) and DSC is the universal detector for measuring a wide variety of transitions in pharmaceutical materials. These include measurement of amorphous structure, crystallinity (and polymorphs), drug-excipient interaction and many other applications. 

Calteridol calcium is used as a chelating excipient in a parenteral formulation and was chosen as an example for two reasons. It contains water associated with a metal cation and thus represents a Class 3 hydrate. In addition, water is also contained in channels, as with the second example. What is unique about the calteridol system is that a single crystal structure has been solved for the tetra-decahydrate (reactant) and the tetra-dihydrate (product) using the same crystal. This procedure permits an interesting look not only into the structural differences but also into the energetic differences of the water environment through thermal analysis. A similar study was performed on the dihydrate and trihydrate phases of di-sodium adenosine 5 -triphosphate [25]. 

Fan CF, Olafson BD, Blanco M, Hsu SL (1992) Application of molecular simulation to derive phase-diagrams of binary-mixtures. Macromolecules 25(14) 3667-3676 Flory PJ (1953) Principles of polymer chemistry. Cornell University Press, Ithaca Forster A, Hempenstall J, Tucker I, Rades T (2001) Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int J Pharm 226(1-2) 147-161... 

Forster A, HempenstaU J, Tucker 1, Rades T. Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int J Pharm 2001 226(1-2) 147 161. 

Since the 1969, when Jacobson and Rieir [83] demonstrated that the stability of penicillins with various tablet lubricants could be predicted from thermal analysis, many attempts have been made to use both DSC and DTA as the basis of compatibility prediction. The basis of the method is to blend the drug under investigation and the excipient at the 1 1 level and to scan through major... 

It was recognized quite some time ago that DTA analysis could be used to deduce the compatibility between a drug substance and its excipients in a formulation. The effect of lubricants on performance was as problematic then as it is now, and DTA proved to be a powerful method in the evaluation of possible incompatibilities. Jacobson and Reier used DTA to study the interaction between various penicillins and stearic acid [17]. For instance, the addition of 5% stearic acid to sodium oxacillin monohydrate completely obliterated the thermal events associated with the antibiotic. Since that time, many workers employed DTA analysis in the study of drug-excipient interactions, although the DTA method has been largely replaced by differential scanning calorimetry technology. 

Thermal methods have found extensive use in the past as part of a program of preformulation studies, since carefully planned work can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [2], It should be noted, however, that the use of differential scanning calorimetry (DSC) for such work is less in vogue than it used to be. Nevertheless, in appropriately designed applications, thermal methods of analysis can be used to evaluate compound purity,... 

TG is a powerful adjunct to DSC studies, and are routinely obtained during evaluations of the thermal behavior of a drug substance or excipient component of a formulation. Since TG analysis is restricted to studies involving either a gain or a loss in sample mass (such as desolvation decomposition reactions), it can be used to clearly distinguish thermal events not involving loss of mass (such as phase transitions). 

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