Automation Opportunities

Laboratory automation is widely used in the pharmaceutical industry to support drug discovery, nonclinical and clinical drug development, and quality control. Analytical applications for which automation is commonly utilized 

HPLC itself is now considered to be a fuUy automated system. Once the solutions are placed in vials and sample sequence is programmed into the software, the auto-injector injects as stated in the sample sequence and it runs as specified in the instrument method. Many types of software, once programmed, also allow integration, processing, and reporting of an entire HPLC run to be performed automatically once the run is completed. 

The focus of automation is not solely on HPLC anymore (since it is automated), but also includes the sample preparation procedure for drug products since it involves many labor intensive steps (weighing, addition of sample solvent, extraction procedure, mixing, filtration, additional dilutions, second mixing, etc.). So, if the sample preparation procedures are automated and combined with HPLC, then the entire analysis is said to be fully automated whether it is for assay, CU, blend analysis, or even for dissolution testing. Such automated workstations are currently available from number of vendors (Caliper Life Science, SOTAX Inc.), but their ability to integrate with HPLC or UV spectrophotometer is left to the end users. This open-ended option depends on the end user requirements. 

Hyphenated techniques utilizing HPLC plays very important role in drug development process, especially LC-MS. The power of LC combined with an universal detector is an optimal combination to determine related substances and peak homogeneity. Selected articles are referenced for the reader [30, 49,50]. 

Challenges for HPLC method development are for combination products where more than one active is present in the same formulation. Since degradation products are of big concern from a safety perspective, HPLC will continue to be utilized as a major separation technique during formulation development to develop the most safe and efficacious formulations to be used for human use. Many different types of bonded phases are currently available for routine HPLC analysis in addition, very selective and sensitive detection techniques can be integrated with HPLC to help an analytical chemist control the final quality of the drug product. Furthermore, the availability of this technique makes it the first and sometimes the only choice for the analysis of degradation products. 

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Additional needed process equipment was evaluated, selected, purchased, and set up. Automation opportunities were defined, and process control instruments were tested, purchased, and installed. An existing clean (HEPA-filtered) area was upgraded for the final isolation of the dilevalol hydrochloride made in New lersey—this was needed to serve the requirements for the parenteral dosage form. 

As pointed out in Chap. 5, replacing simple columns by complex columns tends to reduce the vapor (and heat) load but requires more of the heat to be added or removed at extreme levels. This means that the introduction of complex columns in the design might prejudice heat integration opportunities. Thus the introduction of complex distillation arrangements needs to be considered simultaneously with the heat integration. This can be carried out manually with some trial and error or using an automated procedure such as that of Kakhu and Flower. ... 

The graphics capabiUties of the CAD/CAM environment offer a number of opportunities for data manipulation, pattern recognition, and image creation. The direct appHcation of computer graphics to the automation of graphic solution techniques, such as a McCabe-Thiele binary distillation method, or to the preparation of data plots are obvious examples. Graphic simulation has been appHed to the optimisation of chemical process systems as a technique for energy analysis (84). 

Compatibility physieal influenee with tool ehemieal methods of sample preparation and the stage of determination based on any prineiple of an analytieal signal generation, the opportunity of automation of a sample preparation stage, eontrol, modeling of eonditions of analytieal proeess opens prospeets for their use in the analysis of food-stuffs, environment objeets, geologieal samples, ete. 

Setup an Automated Test Series. Before testing can begin the user must identify the specimen bars in the magazine and specify the test conditions. This is accomplished with setup routines which prompt the user to define the test series. At various points the user is given the opportunity to go back and correct erroneous entries. The information provided by the user is stored in a queue file to be accessed later by the data acquisition software. 

Major advantages of LVI methods are higher sensitivity (compare the 100-1000 iL volume in LVI to the maximum injection volume of about 1 iL in conventional splitless or on-column injection), elimination of sample preparation steps (such as solvent evaporation) and use in hyphenated techniques (e.g. SPE-GC, LC-GC, GC-MS), which gives opportunities for greater automation, faster sample throughput, better data quality, improved quantitation, lower cost per analysis and fewer samples re-analysed. At-column is a very good reference technique for rapid LVI. Characteristics of LVI methods are summarised in Tables 4.19 and 4.20. Han-kemeier [100] has discussed automated sample preparation and LVI for GC with spectrometric detection. 

Very few published data exist on the evaluation of automated systems, though one report has been made of an automated absorption assay using Caco-2 cells cultured on both sides of polycarbonate membranes [93], The concept of culturing cells on the lower sides of the membranes was investigated as a means of improving the opportunity to study transport in the secretory basolateral to apical direction. However, this approach resulted in increased variability and impaired active transport properties of the cell monolayers, and was therefore not recommended. 

The most perspective are the methods based on application of nonequilibrium low-temperature plasma [3], They have a number of advantages smaller dimensions of the equipment, opportunity to automate both the process and quality control of processed environment, low involvement of human resources, opportunity to use new solutions, though poorly investigated, but having useful potential and properties. The basis for the process is the contact plasma discharge on the surface of a liquid phase formed between an electrode in gas phase and surface of the liquid, in which the second electrode is immersed. 

Simpler plants are friendlier than complex plants because they provide fewer opportunities for error and because they contain less equipment that can cause problems. Often, the reason for complexity in a plant is the need to add equipment and automation to control the hazards. Simplification reduces the opportunities for errors and misoperation. For example, (1) piping systems can be designed to minimize leaks or failures, (2) transfer systems can be designed to minimize the potential for leaks, (3) process steps and units can be separated to prevent the domino effect, (4) fail-safe valves can be added, (5) equipment and controls can be placed in a logical order, and (6) the status of the process can be made visible and clear at all times. 

Tool builders Catalysis opens new opportunities for automated tool support in modeling, consistency checking, traceability, pattern-based reuse, and project management. Read the book. 

GF method calculations are simplified by the systematic behavior of the G matrix elements (Decius 1948). MUBFF calculations, however, are somewhat complicated by the force constants representing interactions between non-bonded atoms— these can be tedious to express in terms of internal coordinates. Computer programs have been written to partially automate calculations, thereby reducing the necessary effort and minimizing opportunities for errors (e.g., Schachtschneider 1964 Gale and Rohl 2003). 

The use of large-scale automated perfusion systems has allowed for several oocytes to be tested in parallel and presents an opportunity for high-throughput drug screening. For example, the Robooctye system (see... 

Additional advantages of process analyzers are the possibility to automate all or most parts of the analysis to offer the opportunity of a 24/7 unattended operation. On the downside, the level of complexity and upfront effort during the design, implementation and even maintenance stages can be high and require specialized expertise. 

Supply chain safety— to protect the products and services on which our economy and society depend. The opportunities for chemical scientists include improved security plans at chemical production sites, automated detection systems that can sense agents inside of closed containers, and improved placarding of railroad tank cars. 

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