Blending uniformity study

Fig. 9 Sampling locations from a V-shaped blender for a blend uniformity study. The open circles represent sample locations. 

How much of a crystallizable material X can I blend uniformly into a polymer until it starts to form crystals A series of blends with increasing amount of X is prepared. The samples are studied by WAXS (cf. Sect. 8.2) using laboratory equipment. Crystalline reflections of X are observed, as X starts to crystallize. Peak areas can be plotted vs. the known concentration in order to determine the saturation limit. Think of X being Ibuprofen and Y a polystyrene-(7 )-polyisoprene copolymer, and you have an anti-rheumatism plaster. 

Only 19 batches of drug B were considered suitable for the validation study. This number is shy of our stated goal of a minimum of 20 batches. We therefore will want to supplement the data from the original 19 batches. This effort should be coordinated with the blend uniformity testing. 

Granulation studies (if applicable) to include sieve analysis, bulk density, moisture, blend uniformity, etc. 

M. Popo, S. Romero-Torres, C. Conde, and R. J. Romanach, Following the Progress of a Pharmaceutical Mixing Study via Near-Infrared Spectroscopy Blend Uniformity Analysis Using Stream Sampling and Near Infrared Spectroscopy, AAPS PharmSciTech, 3, 1 (2002). 

Finally, the off line blend uniformity measurement is typically made once each time the process is optimized, this may only happen a few times during the development of a drug product. Once the blend time is set, it will be blended blindly. This is due to the effort and expense of an offline blend imiformity study. 

Many of the techniques described above, excipient compatibility, blend uniformity by HPLC dissolution, and content uniformity/assay by HPLC can be effectively automated by robotic sample preparation. Each of these techniques requires that the sample under study be dissolved in an appropriate solvent and fully extracted from any excipients. There are a number of commercially available products that have proven to be effective and robust in this sample preparation role. This robotic process can reduce both the analyst hours required to prepare a number of samples, and turnaround time on the sample analysis, since the robotic systems will operate unattended over night and on weekends. There is of course a cost to pay for laboratory automation. There is a significant capital cost, and then an ongoing maintenance cost for the continued operation of the system. Also it is critical that a specialist be available in-house to care for the system, develop the methods, and troubleshoot any issues with the system. The cost of the system and specialist must be weighed against the advantages of speed and lab capacity enhancement realized with a successful automation implementation. 

It turns out that in low-viscosity blending the acdual result does depend upon the measuring technique used to measure blend time. Two common techniques, wliich do not exhaust the possibilities in reported studies, are to use an acid-base indicator and inject an acid or base into the system that will result in a color change. One can also put a dye into the tank and measure the time for color to arrive at uniformity. Another system is to put in a conductivity probe and injecl a salt or other electrolyte into the system. With any given impeller type at constant power, the circulation time will increase with the D/T ratio of the impeller. Figure 18-18 shows that both circulation time and blend time decrease as D/T increases. The same is true for impeller speed. As impeller speed is increased with any impeller, blend time and circulation time are decreased (Fig. 18-19). 

A study on the batch processing and characterisation of microcellular foamed HDPE/isotactic PP blends is reported. The blends were used to produce materials with a variety of crystaUine and phase morphologies to enhance the subsequent microcellular foaming. Much finer and more uniform foams were produced with the blends than with neat HDPE and isotactic PP. The mechanical... 

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