Process analytical technologies content uniformity

The first demonstration of solid state fluorescence of API dates back to 1961, while its in-line use for final drug product manufacturing was not demonstrated until recently." While in its infancy as a process analytical technology for real-time monitoring and product parametric real-time release, the applications identified and in some instances demonstrated include (i) blend endpoint API content nniformity detection " (ii) segregation monitoring or API content at various process critical control points and (iii) at-line tablet content uniformity determination. The fundamentals of solid-state luminescence spectroscopy for pharmaceutical solids has been covered by Brittain."... 

M. Blanco, M. Alcala, J.M. Gonzalez and E. Torras, A process analytical technology approach based on near infrared spectroscopy tablet hardness, content uniformity, and dissolution test measurements of intact tablets, J. Pharm. Sci, 95, 2137-2144 (2006). 

M. Blanco, M. Alcala, Content uniformity and tablet hardness testing of intact pharmaceutical tablets by near infrared spectroscopy. A contribution to process analytical technologies. Anal. Chim. Acta, 557, 353-359 (2006). 

J. J. Moes, M. M. Ruijke, E. Gout, H. W. Frijlink, and M. 1. Ugwoke, Application of Process Analytical Technology in Tablet Process Development Using NIR Spectroscopy Blend Uniformity, Content Uniformity and Coating Thickness, Int. J. Pharm., 357,108 (2008). 

Manufacturing, analytical, and quaUty control procedures are thus estabhshed. Specifications for taw and in-process materials, as well as for final products per USP/NF and in-house standards are also determined. Process and formula vaUdation assures that each technological procedure in manufacture accomplishes its purpose most efficiently, eg, blending times for powdered mixtures in tableting, and that each formula ingredient is present in optimal concentrations (12). Thus, it serves to ensure process control (qv), reproducibiUty, and content uniformity. 

Solid dosage forms Solid dosage forms, e.g., tablets and capsules, are by far the most common for several reasons. The production of relevant doses is easy to accomplish, and scale-up is usually a standard technological process. All divided dosage forms have strict requirements for uniformity of content, i.e., a statistical sampling of the batch should show a uniform distribution of the active component. This requirement is especially important for units with very small amounts of the active component, i.e., from a few micrograms per dose to 50 mg. This has often led to automated analytical methods to cope with the large number of samples. 

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