Blend uniformity

The continuously stirred mill can be fed by screw feeders from several material bins siiTuiltaneously, thus blending uniform compositions, without incurring problems of transporting imperfectly blended or agglomerated mixtures. A series of mills may be used with decreasing media size and increasing rotary speed to achieve desired fine-particle size. No additional feed pumps are needed. 

The effect on the process of a change in operation of the mixer system (impeller, baffles, etc.) is the final measurement of performance. Thus, operations such as blending, uniform particle suspension, reaction, gas absorption, etc., may be acceptable under one physical system and not so to the same degree under a slightly modified one. The ratio per unit volume on scale-up must be determined experimentally. 

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. 

Solubility The ability of one material to dissolve in or blend uniformly with another. 

The most recent converts are in the health care industry. Pharmaceutical and biological applications have become myriad since the early 1980s. The first widespread application was for the identification/ qualification of incoming raw materials. Since then, applications have appeared for moisture (bound and free), blend uniformity of powders, tablet and capsule assays, counterfeiting, polymorphism, degree of crystallinity, hardness (of tablets), dissolution prediction, isomerism, as... 

Techniques commonly used to produce fibrous webs include the wet laid, dry laid carded, and meltblown processes. The wet laid or paper making process is the predominant method for several reasons. The wet laid process, configured properly, allows for the blending of cellulosic and polymeric components. Also, the ability to use short cut length and fine denier fiber provides for consistent blending, uniform formation, and controlled pore structure. 

For the blend uniformity application, the primary concern is overall heterogeneity within the sample. This is directly indicated by the width of the distribution and is quantitatively measured as the percent standard deviation relative to the mean (%SD). The %SD value obtained from the PLS scores distribution from each of the six imaged tablets is noted on the histograms in Figure 8.15(A-F). The value of %STD consistently decreases as the blending quality of the sample improves. 

The application of NIRS does not resolve all concerns associated with accurate blend uniformity determination. Key questions arise, such as (1) is the NIR beam sampling within a unit dose and (2) are an effective number of unit doses being sampled throughout a blend These questions are not limited to NIRS, but are applicable to any diffuse reflectance optical technique. 

D.S. Hausman, R.T. Cambron and A. Sakr, Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity, Int. J. Pharm., 298, 80-90 (2005). 

Determination of the physical properties of formulations such as blend uniformity and particle size. 

Ray K. Validation of a Novel Process for Large-scale Production of Powdered Media Evaluation of Blend Uniformity. Presented at the Raw Materials and Contract Services Conference (Williamsburg Bioprocessing Eoundation), St. Louis, MO, May 19-21, 1999. 

Technical Report No. 25 Blend Uniformity Analysis Validation and In-Process Testing. J Pharm Sci Technol 1997 Supplement, 51(S3). 

There are two primary concerns with powder handling that cannot be overlooked when scaling processes achieving reliable flow and maintaining blend uniformity. To address these issues when scaling processes, knowledge of how powders flow and segregate is required. 

Prescott JK, Garcia TP. A solid dosage and blend uniformity troubleshooting diagram. Pharm Technol 2001 25(3) 68-88. 

Sampling errors may occur in some powder blends, sampling devices, and techniques that make it impractical to evaluate adequacy of mix using only the blend data. In such cases, it is recommended that in-process dosage unit data be used in conjunction with blend sample data to evaluate blend uniformity. 

For example, is a 2 g test sample from a 1000 kg consignment or bulk batch adequate for the purpose It may be under appropriate circumstances. If not, how much material needs to be taken Recent draft guidance to the pharmaceutical industry from the FDA recommends that for blend uniformity sample sizes no more than three times the weight of an individual dose should be taken. 

Food Drug Administration, Center for Drug Evaluation and Research, Draft Guidance for Industry, August 1999, ANDAs Blend Uniformity Analysis. 

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