Active pharmaceutical measurement

It is a general requirement for an optimal therapeutic effect that the active pharmaceutical ingredient (API) is delivered to the site of action in order to provide effective but not toxic concentration levels. Therefore, studies to measure BA are of great importance in order to support new drug product applications. Thus, data on the BA of orally administered drug products is a general requirement to the development... 

Control weighting, measuring, monitoring and test equipment that is critical for assuring the quality of intermediates or APIs (active pharmaceutical ingredients) should be calibrated according to written procedures and an established schedules. 

Active pharmaceutical ingredients (API) can be identified using many different analytical approaches. A Raman spectroscopy method may not be the most common or economical but it does offer significant advantages. These include rapid, sensitive analysis, information-rich spectra, minimal or no sampling [32]. Handheld Raman spectrometers now allow the measurement to be taken to samples allowing analysis at the point of receipt and not just in a... 

Among several techniques possible to design process measurement tools, those based on spectroscopic techniques such as near-infrared (NIR), infrared (IR), Raman, terahertz (THz), fluorescence and UV-Vis absorption offer obvious advantages for PAT owing to their speed, compactness and versatility. Spectroscopic assessment yields chemical information such as content of active pharmaceutical ingredient (API) or of the relative concentration of different ingredients in a suspension, a blend, a composite preparation/formulation. However, physical information may also be obtained that is directly or indirectly related to, for example, particle size, porosity and density. Physical information is particularly valuable in characterisation of manufacturing processes and for reliable prediction of finished product properties. 

Pan, T. Barber, D. Coffin-Beach, D. Sun, Z. 8t Sevick-Muraca, E.M., Measurement of low-dose active pharmaceutical ingredient in a pharmaceutical blend using frequency-domain photon migration /. Pharm. Sci. 2004, 93, 635-645. 

The active pharmaceutical ingredient in a low-dose formulation is typically a small molecule, designed to meet a small particle size requirement for uniformity purposes, and can be susceptible to effects of static charge and segregation. The impact of static charge on the accuracy of blend uniformity measurements (i.e., sampling bias) is discussed in the next section. 

Wavelength repeatability is a measure of the precision of wavelength measured. The bandwidth refers to the width of an emission band (from the monochromator) at half peak height. This value, normally provided by the manufacturer is accepted. Using a mercury vapor lamp one can also check the spectral width. A number of well defined emission lines at 243.7, 364.9, 404.5, 435.8, 546.1, 576.9, and 579 nm can be used to check spectral bandwidth. However, the accuracy of the absorbance measured is dependent on the ratio of spectral bandwidth to the normal bandwidth (NEW) of the absorbing species. Most active pharmaceutical compounds have a normal bandwidth of approximately... 

The rate and extent to which the active moiety is absorbed from a pharmaceutical dosage form and becomes available at the site(s) of action. Reliable measurements of drug concentrations at the site(s) of action are usually not possible. The substance in the general circulation, however, is considered to be in equilibrium with the substance at the site(s) of action. Bioavailability can be therefore defined as the rate and extent to which the active pharmaceutical ingredient or active moiety is absorbed from a pharmaceutical dosage form and becomes available in the general circulation. Based on pharmacokinetic and clinical considerations it is generally accepted that in the same subject an essentially similar plasma concentration time course will result in an essentially similar concentration time course at the site(s) of action. 

Unstable compounds are problematic. A sample purified in the laboratory might have a short shelf-life and poor performance as a standard. Compounds altered by assays are also inconvenient. For example, substituted benzylic alcohols can dehydrate under acidic HPLC conditions, or carboxylic esters can hydrolyze in aqueous mobile phase. An impurity isolated from an active pharmaceutical ingredient as an organic salt of an organic compound poses two problems at once. The analyst must account for both the acid and the base. In the case of a toluenesulfonic acid salt of an aliphatic amine, two different methods of detection might be needed. The toluenesulfonic acid in a reverse-phase HPLC assay can by monitored by UV light, but the aliphatic amine, with no chromophore, must be measured by a different technique. 

Measures should be taken to ensure that no person affected by a disease in a communicable form or having open lesions on the exposed surface of the body is engaged in any production step involving direct contact with the active pharmaceutical ingredients. 

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