Factors that Adversely Affect Processing

A good understanding of key process inputs and parameters may be obtained through careful statistical design of experiment and will lead to a good understanding of how robust a process is. Factors that can adversely affect process robustness include non-selective chemistry or unwanted side reactions, physical and chemical stability of the reactants or reagents, and the complexity of the process separation train. 

Like other chemical reactions, the chemical structure of the reactants, the concentrations, reaction temperature, reaction time, emulsification, and stirring are major factors that can affect this process and thus the formation and quality of the microcapsule. Furthermore, reactants should be compatible with the core material without any adverse reactions. 

Dose-response assessment is the process of characterizing the relationship between the dose of an agent administered or received and the incidence of an adverse health effect in e.xposed populations, and estimating the incidence of the effect as a function of e.xposure to the agent. This process considers such important factors as intensity of exposure, age pattern of exposure, and possibly other variables that might affect response, such as sex, lifestyle, and other modifying factors. 

When assessing the robustness of a process, several factors that can adversely affect it include non-selective or side reactions that might produce adverse effects and impurities physical and chemical stability of the materials involved and complexity of the separation train of the processes. 

Water Uptake. There is evidence to suggest that water uptake caused by capillary forces is the crucial factor in the disintegration process of many formulations. In such systems the pore structure of the tablet is of prime importance and any inherent hydrophobicity of the tablet mass will adversely affect it. Therefore, disintegrants in this group must be able to maintain a porous structure in the compressed tablet and show a low interfacial tension towards aqueous fluids. Rapid penetration by water throughout the entire tablet matrix to facilitate its breakup is thus achieved. Concentrations of disintegrant that ensure a continuous matrix of disintegrant are desirable and levels of between 5 and 20% are common. 

Sudden death has occurred in patients with preexisting heart disease on antidepressant therapy. It may be difficult, however, to separate a causally related drug effect from a cardiovascular incident precipitated by other factors and only by chance coincident with drug therapy. Furthermore, Roose ( 418), who has summarized the literature, noted that major depressive disorder occurs frequently after a myocardial infarct and may adversely affect the recovery process. 

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