41 Drug Discovery & Pharmaceuticals Sample analysis in practice
Figure 3. Working principle of the Planetary Ball Mill
Processing the sample perfectly
If the suspension is too runny, the particles fl oat past the grinding tools, in this case grinding balls. If the suspension is too viscous, the energy of the grinding tools are decelerated. The amount of liquid must always be corrected anew during the grinding process, since more and more new surfaces develop which must to be wetted. The critical temperature of the grinding sample should not be exceeded. Aldditionally, the effect of the increased agglomeration with high temperatures must be observed.
In further proceedings, in order to achieve a smaller fi nal fi neness, the grinding balls are exchanged step by step for smaller grinding balls. Here the degree of comminution should be checked via particle size analysis. The degree of comminution Z is a value from the chemical and mechanical process technology and offers information in regards how well a comminution process has worked.
It is defi ned as proportion of the largest particle diameter D in the base sample to the largest particle diameter d in the comminuted product [1,2,3].
A comminution factor of 1 means that no comminution has occurred. If the largest particles, after comminution still measure half of their original diameter so is Z=2.
The more forceful the comminution, the larger becomes n. So should the degree of comminution with constant temperature and exact solvent ratio in the further course barely change, so should the grinding balls be exchanged for the corresponding amount of smaller grinding balls [3].
This comminution process can be utilised to examine antibiotics in regards to quality in accordance with the guidelines of US Pharmacopoeia and European Pharmacopoeia. Examples of such supplements are gentamicin, neomycin, cefadroxil or bethanechol chloride. During the production inorganic contaminations (for example, heavy metals) can occur. This detection of this possible contamination is an additional part of the analysis. With the assistance of stripping voltammetry can the successfully comminuted supplement be examined for metal ions. These ions mostly originate from mercury containing thimerosal, which is utilised as a preserving agent for pharmaceuticals and cosmetics. The protection from microbial contamination is the reason for this. This compound is used for eye, nose and ear drops and tattoo ink, as well as cleaning and storage liquids for contact lenses. These delicate samples in their complex composition require correct sample preparation in a system which conveys the samples in optimal conditions without falsifying them [1].
Conclusion
The fast paced development of analytical methods in pharmaceutical technology requires always new adaptation of the comminution of the demanded parameters. In modern methods mostly the smallest obtainable particle size is of interest. Therefore the comminution mechanisms are continually optimised down into the nano range and matched to the characteristics of the corresponding samples.
In classical methods like the comminution with a hand mortar or mortar mill, the focus is more on the gentle comminution. Biological samples, like for example herbs or medicinal plants, would due the development of thermal effects caused by the high energy impact during nano grinding, lose their pharmacologically active substances. Therefore comminution technologies cannot be evaluated according to their effi ciency, but instead a comminution technology must be selected according to task and analysis in order to obtain optimal results.
If the emphasis is only on particle size, it has been shown that the latest advancements in the development of nano mills lead to much quicker grinding durations, where a particle size below 0.1 µm can be obtained.
References
1. K.H. Bauer, K.H. Frömming, C. Führer, Lehrbuch der Pharmazeutischen Technologie, 7. überarbeitete und erweiterte Aufl age (2002)
2. K. Hertwig, L. Martens, Chemische Verfahrenstechnik 2. überarbeitete Aufl age, (2011) 3. M. Stieß, Mechanische Verfahrenstechnik 2, 2., überarbeitete Aufl age, (2011) 4.
www.fritsch.de
Read, Share and Comment on this Article, visit:
www.labmate-online.com/article New Range of Anti-Eculizumab Antibodies Introduced
Bio-Rad Laboratories, Inc has announced the launch of a range of recombinant monoclonal anti-idiotypic antibodies that inhibit the binding of eculizumab (Soliris) to its target, complement C5 protein. These anti- eculizumab antibodies detect free drug and are designed for use in drug level monitoring assays and biosimilar development.
The new range of recombinant monoclonal anti-idiotypic antibodies is comprised of four inhibitory antibodies that are highly specific for the humanised IgG2/4 kappa monoclonal antibody drug, eculizumab, a biotherapeutic that is used to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. The anti-eculizumab inhibitory antibodies can be used to quantify the level of eculizumab in patient samples and they may also be used in bioanalytical assays for biosimilar development. An antibody pair is suitable for the development of a pharmacokinetic (PK) bridging ELISA, and antibodies of high, medium, and low affinity can be used as a positive control or calibrator in an anti-drug antibody assay.
The recombinant monoclonal anti-idiotypic antibodies are generated using the Human Combinatorial Antibody Library (HuCAL®) and CysDisplay®, a proprietary method of phage display with guided selection methods to obtain highly targeted reagents. The recombinant production method also ensures a consistent and secure supply.
“Bio-Rad’s portfolio of highly specific anti-biotherapeutic antibodies continues to expand, providing critical reagents for use in preclinical and clinical development of biosimilars, and for therapeutic drug monitoring of patients,” said Amanda Turner, Bio-Rad Product Manager, Life Science Group. “Our unique anti-eculizumab antibodies are well characterised and have been validated for use in PK and immunogenicity assays. Adding new specificities to our portfolio will help researchers overcome challenges associated with assay design and sensitivity,” she added.
The anti-eculizumab antibodies are approved for in vitro research and for commercial applications of in vitro testing services that support preclinical and clinical drug and biosimilar development and patient monitoring.
48428pr@reply-direct.com
Fully Automated Water Conductivity Testing Safeguards Compliance with USP<645>
USP<645> describes conductivity as key parameter for measuring the purity of ultrapure water and water for injection. Compliance with USP<645> is key for manufacturers from the pharmaceutical industry. However, following the three stage test procedure defined by the standard can be a challenge, particularly if the testing is performed manually. A dedicated Metrohm system provides a fully automated solution to this challenge reducing the risk of error while increasing productivity.
USP<645> describes a cascade of three tests, which have to be performed in sequence. If testing at stage one fails, the procedure defined for stage-two testing has to be performed, which in case of failure has to be followed by the stage-three testing. Failure at stage three equals an out of spec sample. The risk of human error is considerable at each stage, as thorough working is required and conditions must be met such as a maintaining a specific temperature in the solution.
The Metrohm system for conductivity testing according to USP<645> provides a fully automated solution to this challenge. All that is required from the operator is filling the sample into a beaker and placing it on the system’s autosampler. Conductivity testing in whole series of samples is then performed completely unattended while tiamo software makes sure data integrity is maintained and compliance with regulatory standards such as FDA 21 CFR Part 11 is met.
48519pr@reply-direct.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72
