Blend uniformity, assessment

Encapsulation assessment Appearance target (moisture test) and drying cycle Visual-performed measurement of drying cycle Blend uniformity Tools available for online... 

Mixing equipment should be evaluated for the presence of dead spots, which may affect blend uniformity (i.e., valves and discharge ports). All production equipment should be assessed for suitability of use in the manufacturing process this should include ease of cleaning and ability to maintain control parameters (including sterilization, if applicable). Test results consistently at or near the upper or lower limits indicate problems with the process or incompatibility with the equipment. All equipment should be adequately identified in each batch record. A detailed description of all equipment should be given in the submission as well. The suitability of the equipment for the process can be... 

For this reason and in the interest of operator safety, it is the authors preference that for highly potent/toxic compounds, non-intrusive techniques such as PAT should be used to assess blend uniformity. If PAT is not available, then sampling of the final product should be an acceptable alternative to blend sampling. Sampling requirements are discussed elsewhere in this chapter. 

The guidance document recommends that during the manufacture of demonstration and process validation batches, the following uniformity characteristics be assessed (1) the powder blend, (2) the in-process dosage units, and (3) the finished product. Each attribute should be determined independently. It is further recommended that the following steps be used to identify sampling locations and acceptance criteria prior to the manufacture of the exhibit and/or validation batches ... 

The uniformity of the active ingredient in the powder blend prior to granulation can be assessed directly by taking samples of the powder blend from the granulator. This may be insightful during formulation development so that the impact of each of the unit operations on the uniformity of the finished granulations and the finished product can be clearly understood. 

Garcia T, Wilkinson S, Scott IF. 2001. The development of a blend-sampling technique to assess the uniformity of a powder mixture. Drug Dev. Ind. Pharm. 27(4) 297-307. 

Kausar N, Cornelius V, Snowden MJ, Mitchell J, Mwesigwa E, Do N, Farrell T. 2006. Assessment of low-dose content uniformity of indomethacin in excipient blends using FT-Raman mapping spectroscopy. AAPS Annual Meeting and Exposition, San... 

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