1. Field of the Invention
The present invention generally relates to a method and apparatus for sampling powder, and moves specifically to a method and apparatus for powder sampling which obtains undisturbed powder samples.
2. Related Art
Powdered materials are used in a wide range of industries. For example, an estimated 80% of pharmaceutical products take the form of tablets, which are compacts of powders. Powdered ingredients such as starches, flour, and sugars are essential raw materials in the food industry. Inorganic powders, such as oxides, nitrides, and carbides are used as raw materials in the ceramic industry. Detergents, abrasives, cosmetics, fertilizers, catalysts, etc., also involve processing powdered components.
Achieving homogeneous and well-characterized blends of powders and granules is a critical step in the manufacture of pharmaceutical tablets. Ineffective powder blending can result in increased variability in the contents of potent components in tablets, often resulting in rejection of finished product due to poor quality. If mixing inhomogeneities could be identified and/or avoided during the manufacturing process, fewer batches would be rejected, thus reducing manufacturing costs for existing products and perhaps decreasing time-to-market for new products.
At the present time, blending of granular materials is largely an art rather than a science. The ability to design and accurately assess a mixing process for a high potency drug is limited. Recognition of this problem has recently resulted in lawsuits and in tightening of FDA regulations. The situation is complicated by the lack of effective techniques for characterizing powder mixtures. In fact, the state of the art in sampling procedures (the thief probe) is often so inaccurate that it is possible for a high quality batch to be rejected due entirely to sampling error. Poor sampling capabilities have resulted in a lack of rigorous quantitative evaluations of actual powder mixing processes, further hindering both process development and quality control.
Characterization of homogeneity in a powder system is usually attempted by taking and analyzing discrete samples. The most common approach in stationary powder systems is to use a thief probe to withdraw samples from different locations. Thief samplers belong to two main classes, side-sampling and end-sampling. A typical side-sampling probe has one or more cavities stamped in a hollow cylinder enclosed by an outer rotating sleeve. The sleeve has holes that align with the cavities, allowing adjacent powder to flow into the cavities. An end-sampling thief has a single cavity at the end of the probe; such cavities can be opened and closed in a controlled manner. In both cases, the thief is introduced into the powder with the cavities closed. Once insertion is complete, the cavities are opened, allowing the powder to flow into them. The cavities are then closed, and the thief is withdrawn, removing samples from the mixture.
In principle, the homogeneity of the mixture may be statistically estimated from these samples. However, this estimate is meaningful only if the probe itself does not introduce errors. As mentioned above, this is not always the case. Errors are often introduced both when the theif probe is inserted into the powder bed and when powder flows into the thief cavities. In any sampling scheme, the experimentally measured variance, σe2,is actually a combination of the true variance resulting from the mixing process, σm2, the variance introduced by sampling error, σs2, and the variance resulting from chemical analysis, σa2. In addition, for granular materials, any sample is composed of a finite number of particles, and there is a residual irreducible variance σr2 i.e.,σe2=σm2+σs2+σa2+σr2  (1)In an ideal situation, σs2, σa2 and σr2 are negligible, and σe2 (the variance subject to USP rules) is almost identical to σm2 (the true variance). Unfortunately, thief probes often bias measurements to the point that sampling uncertainty is a large fraction of the measurement. Thief probes often introduce two types of errors: (i) the mixture is extensively disturbed when the thief probe is inserted into the powder bed, and (ii) particles of different size flow unevenly into the thief cavities. As a result of such errors, a homogeneous mixture can be deemed inadequate due entirely to sampling error.
Accordingly, what is needed, but has not heretofore been provided, is a powder sampling tool that preserves the homogeneity of the mixture and minimizes disturbance of the powder bed.
USPTO Backgrounds
USPTO Backgrounds