Impurities formulation-specific

Similarly, impurity profiles may change when the formnlation is modified or a scale-up of a specific formulation is made. Pharmacentical formnlations are a complex physiochemical system that may resnlt in impnrities due to reactions between API and pharmacentical excipients and/or packaging materials. In some cases, degradants that were generated by multiple-step degradation pathways can still react with the API leading to the formation of degradants that can be difficult to identify. 

Dimethylaniline is both a manufacturing impurity in bupivacaine and since it is formulated in injections a possible breakdown product, although hydrolysis of amides is much slower than hydrolysis of esters. The BP uses a spectrophotometric method to assay for this impurity but GC provides a more sensitive and specific method for this determination. 

Excipients bring properties to formulations that facilitate the conversion of the API to a medicine. These functional properties will depend on the particular formulation. For parenteral products, open wound treatments, and ocular treatments, there are specific additional requirements concerning impurities, microbiological load, and endotoxins. However, excipients intended for nonsterile applications very often function, because they are not single chemical compounds. There are other functional or concomitant components frequently present, which are necessary to achieve the required performance (functionality) of the excipient in use. These should be considered separately from any impurities, process residues, or foreign substances that may be present. (In some applications, certain components that have traditionally been considered to be impurities or residues, may actually be concomitant components.) It is important to understand that these other components, whatever their source, may also interact with the API or other excipients. 

Excipients used in injectable formulations have to meet several stringent requirements. A positive identification test uniquely applicable to the excipients is required (e.g., infrared spectrophotometry and chromatography). It is important that manufacturers identify and set appropriate limits for impurities. These limits should be based upon appropriate toxicological data, or the limits described in national compendial requirements. Manufacturing processes should be adequately controlled so that the impurities do not exceed such established specifications. Solvents or catalysts used in the excipient production process should be removed to appropriate levels. If naturally derived, excipients should meet endotoxin levels and may require further testing for bovine spongiform encephalopathy (BSE) /... 

Formulate a statement of the design criteria for the unit. What is the general design criteria What is the design (or the unit) intended to achieve For example, a reactor is usually required to achieve a particular conversion of reactants to products, a distillation column must provide a particular separation, an absorption column provides removal of a specific level of impurity, etc. 

The preclinical stage of drug development focuses on activities necessary for filing an IND/CTA. The completed IND/CTA contains information that details the drug s composition and the synthetic processes used for its production. The IND/CTA also contains animal toxicity data, protocols for early phase clinical trials, and an outline of specific details and plans for evaluation. Process research, formulation, metabolism, and toxicity are the major areas of responsibility in this development stage. Analysis activities that feature LC/MS primarily focus on the identification of impurities, de-gradants, and metabolites. 

Many methods have been developed for the quantitative determination of each class of surfactants. The analysis of commercial surfactants is much more complicated since they may be comprised of a range of compounds within a given structural class, may contain surface-active impurities, may be formulated to contain several different surfactant classes, and may be dissolved in mixed organic solvents or complex aqueous salt solutions. Each of these components has the potential to interfere with a given analytical method so surfactant assays are sometimes preceded by surfactant separation techniques. Both the separation and assay techniques can be highly specific to a given surfactant/solution system. Table 3.4 shows some typical kinds of analysis methods that are applied to the different surfactant classes. 

Due to the high stability of pantoprazole sodium at high pH, the samples to be analyzed were dissolved in 0.1 M NaOH. The method was found to be specific for pantoprazole since it showed no interference from excipients in the formulation, and can separate the potential synthesis impurities and possible degradation products. 

Specific areas where FTIR has provided valuable information include quantitative analysis of active material impurity identification in technical material analysis of volatile components from formulated material and the identification of metabolites. In this paper, we will discuss the results from these studies and describe some of the problems we encountered. We will also discuss some of the new developments in FTIR that might prove useful in pesticide analysis. 

The API Assay, the Assay of Impurities and Product Stability. The central independent analytical research and quality control unit is responsible for the analytical release of both the API and the formulated drug product for the drug development programs. The central independent QC unit provides all the analytical data needed to build the analytical specification for the IND. It is recognized by those involved that the IND is a relatively raw document compared with the later NDA, which is built on data from a more developed process situation, using more refined analytical techniques. 

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