Pharmaceutical products buffer system

Table 1 Acids and bases suitable for use as buffer systems in pharmaceutical products...

Glacial and diluted acetic acid solutions are widely used as acidifying agents in a variety of pharmaceutical formulations and food preparations. Acetic acid is used in pharmaceutical products as a buffer system when combined with an acetate salt such as sodium acetate. Acetic acid is also claimed to have some antibacterial and antifungal properties. 

Claims have been made that the TBA does not enter into the product glassy phase.It has, however, also been reported that some TBA is indeed incorporated into the freeze-concentrate. If true, this might raise regulatory problems with pharmaceutical product registration. It is also not yet clear whether at temperatures in the region of Tg, the effect of TBA is unique. For instance, with sucrose-water systems, the presence of a volatile buffer salt (ammonium bicarbonate, acetate, formate) has a more marked effect on the sublimation rate than has TBA. On the other hand, with PVP-water systems, TBA is superior in enhancing the sublimation rate. It thus appears that the choice of excipient can also affect the drying rate. 

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],... 

There seems to be no limit to the types of pharmaceutical systems that can be isolated in the amorphous state. In the literature, samples of sugars, acids, bases, polymers, buffers, inorganics, salts, natural products, proteins, and low-molecular-weight APIs have all been reported to exist in an amorphous form. Likewise, pharmaceutical raw materials, intermediates, and final products that include these amorphous materials are widespread and varied (Table 1). 

The inline dilution system shall allow the preparation of buffers with an inline dilution factor ranging from 1 to 10. This factor determines the ratio of water to concentrated buffer. Larger ratios are of course feasible, but there is a trade-off between the process accuracy and flexibility to be taken into account. The systems shall cope as well with process disturbances and shall be robust again changing process conditions (such as pressure drop in a chromatography column or a sudden change in pressure or flow rate in the primary water supply). The robustness of such systems is crucial since pharmaceutical processes are validated to run in certain predefined limits. Any deviations to such limits will lead to additional investigation costs that could have severe consequences, in the extreme situation the withdrawal of the produced product. 

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