Chemical decomposition, of drug

Similarly, the commercial success of solid dispersion has been limited due to use of higher temperatures (>100°C) or harmful organic solvents, such as chloroform or dichloromethane, which may result in chemical decomposition of drugs and carriers or possible toxicity from the residual solvent. These unacceptable problems led scientists to explore novel alternatives, particularly the cogrinding method, which involves... 

The in vitro degradation profiles of several TDI poly(phosphoester-ure thanes) are shown in Figure 2. It is not possible from this study to correlate the decomposition kinetics with the chemical structure, except for the fact that biodegradability is demonstrated. The in vitro release of 5-FU from PPU-7 is shown in Figure 3. After an initial burst, a reasonably steady and sustained release followed. The UV spectrum of the released 5-FU was identical to that of pure 5-FU, suggesting the chemical integrity of the drug. 

H. Nogami, M. Horioka, Studies on Decomposition and Stabilization of Drugs in Solution. VI. Chemical Kinetic Studies in Aqueous Solution of Diphenhydramine , J. Pharm. Soc. Jap. (Yakugaku Zasshi) 1961, 81, 79 - 83. 

Impurities in drug substances and drug products continue to be a source of great concern, discussion, debate, and research. " These concerns and debates typically center on the potential safety risks associated with impurities due to contamination and the setting of acceptance criteria. However, the bulk of the work being performed in the pharmaceutical industry, with respect to impurities, is focused on the isolation, identification, qualification and quantification of impurities that are found as a result of the manufacturing process or through chemical decomposition. On the... 

Degradation products are those compounds produced through the chemical or thermal decomposition of the analyte. Container/closure adducts are generally the result of an interaction between a drug substance or intermediate with the container/closure material or extracta-bles from these materials. 

As discussed in Chapter 1 (Sections III and TV), the kinetics of drug degradation has been the topic of numerous books and articles. The Arrhenius relationship is probably the most commonly used expression for evaluating the relationship between rates of reaction and temperature for a given order of reaction (For a more thorough treatment of the Arrhenius equation and prediction of chemical stability, see Ref. 13). If the decomposition of a drug obeys the Arrhenius relationship [i.e., k = A exp(—Ea/RT), where k is the degree of rate constant, A is the pre-exponential factor ... 

Degradation is a chemical transformation of the drug substance and can be expressed as a chemical reaction with the specific kinetics. These reactions can have different orders, which are characterized by the different rate of parent compound decomposition. The most common are zero, first and second order reactions. It is not a subject of this chapter to discuss reaction kinetics in details however, specific preformulation-related discussions can be found in reference 6, and a general approach with examples is very well described by Martin [44]. 

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