Active pharmaceutical ingredient parameters

By the time an active pharmaceutical ingredient (API) is made available to an analytical chemist in the formulation development group, most or all of the physical characteristics of an API has already been studied and the information should be available in some sort of a report from the drug substance group or preformulation group. Some of the key parameters that an analytical chemist in formulation development requires from such a report are the solubility and solution stability. 

Characterization starts once the synthetic route has been selected, although there will be opportunities to modify the route if the changes do not impact the final solid state or impurity profile of the final active pharmaceutical ingredient. The primary objective is to understand, through experimentation, the chemical and physical chemical processes involved in the transformation of raw materials to intermediates and products. The primary outcome is a process definition that includes the order of manufacturing steps, process parameter control methodology, process parameter limits, raw material specification, and diagnostic metrics. 

E.C. Achilleos, J.C. Calandranis, and D.P. Petrides. Quantifying the impact of uncertain parameters in the batch manufacturing of active pharmaceutical ingredients. Pharmaceutical Engineering, page 34, July/August, 2006. 

The same authors also applied capillary electrophoresis to the study of benazepril hydrochloride and several angiotensin-converting enzyme inhibitors [43]. Separation of the compounds was performed by means of two phosphate buffers (each 0.1 M) at pH 7 and 6.25, respectively [42], Due to the highest selectivity of the first mentioned running buffer, the same system has been applied for the quantification of benazepril and other compounds in their corresponding pharmaceutical formulations. It was found that the possibility of simultaneous identification and quantification of the active ingredient in the finished products was especially attractive, and that excipients do not adversely affect the results. This article deals with the validation of some parameters of the quantitative analysis, namely linearity, precision, accuracy, and robustness [43],... 

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