Key Operating Parameters

As shown in Table 2, the recommended volume of dissolution medium is 500-1000 mL, with 900 mL as the most common volume when using the basket or paddle apparatus. The volume can be raised to between 2 and 4L, depending on the concentration and sink conditions of the drug, but proper justification is expected. 

The standard temperature for the dissolution medium is 37 0.5°C for oral dosage forms. Slightly increased temperatures such as 38 0.5°C have been recommended for dosages forms such as suppositories. Lower temperatures such as 32 0.5°C are utilized for topical dosage forms such as trans-dermal patches and topical ointments. 

The significance of deaeration of the medium should be determined on a case-by-case basis, as air bubbles can interfere with the test results and act as a barrier to dissolution 

Currently, the Japanese Pharmacopoeia (JP) is the only pharmacopeia that requires a specific sinker device for all capsule formulations. The USP recommends a few turns of a nonreac-tive material wire when the dosage form tends to float (12) (see Chapter 2 for illustrations of the Japanese and USP sinkers). Because sinkers can significantly influence the dissolution 

Sinkers can significantly influence the dissolution profile of a drug. Therefore, the use of sinkers should be part of the dissolution method validation. If equivalent sinkers are identified during the sinker evaluation and validation, the equivalent sinkers should be listed in the written dissolution test procedure. When a dissolution method utilizes a dissolution sinker and is transferred to another laboratory, the receiving laboratory should duplicate the validated sinker design(s) as closely as possible. 

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Operational qualification establishes that an instrument will function according to its specification in the selected environment. The role of OQ can be considered as demonstrating that an instrument s key operating parameters are within specification and there are no unacceptable differences between the parameters... 

Let us assume a standard four-zone SMB unit, in which the complete separation of a binary mixture, constituted of the more retained component A and the less retained component B is to be achieved. In the framework of the Equilibrium Theory, the key operating parameters through which the performance of the SMB can be controlled are the flow rate ratios, rrij, /=l,...,4,in the four sections of the SMB unit, according to ... 

Key operating parameters that may change (or be optimized) throughout a product s development and approval cycle are dissolution sampling time points and dissolution limits or specifications by which the dissolution results should be evaluated. The results generated from the dissolution test need to be evaluated and interpreted based on the intended purpose of the test. If the test is used for batch-to-batch control, the results should be evaluated in regard to the established limits or specification value. If the test is being utilized as a characterization test (i.e., biopharmaceutical evaluations, formulation development studies, etc.) the results are usually evaluated by profile comparisons. 

The process owner should represent and interpret these metrics to the organizations leadership. The metric output from a process is the basis for management and leadership s action in resource deployment and approval of continuous improvement projects. Key operating parameters such as number of nonconformances and regulatory observations against the process should be tracked and factored into the maturity of the process. 

Significantly simpler designs, with increased safety and performance margins in key operational parameters. 

The key operational parameter in free-solution capillary electrophoresis is the pH of the running buffer, as the electroosmotic flow and ionization of the analyte can be regulated by this variable. The role of buffers in capillary electrophoresis has been discussed in detail, with emphasis on buffer concentration, buffer type, and pH effects [10]. The effect of organic solvents on separation and migration behavior has been studied for dipeptides [11] and somatostatin analog peptides [12]. The order of migration as well as the selectivity may be manipulated by organic modifiers in... 

From an operational and regulatory perspective, the challenge is to develop control strategies which are effective in the field, but which are also practical to implement. For example, from a knowledge of the fundamental chemical and physical mechanisms of PCDD/F formation and their relationships to the prevailing physical and chemical conditions, it is possible to identify through laboratory experiments key operational parameters or surrogate emissions... 

The current density is the key operational parameter, affecting not only the system s response time but also strongly influencing the dominant pollutant separation mode. The highest allowable current density may not be the most efficient mode of running the reactor. It is well known that the optimal current density will invariably involve a trade-off between operational costs and efficient use of the introduced coagulant. At the meantime, the current density depends on solution pH, temperature, flow rate, etc. 

The procedure employed is thoroughly described in the instrument instructional manual. Thus, the following sections will deal only with the general operations and key operating parameters. 

The following section is devoted exclusively to the description of the main operations and key operating parameters. 

The internal stress of plasma polymers is dependent not only on the chemical nature of monomer but also on the conditions of plasma polymerization. In the plasma polymerizations of acetylene and acrylonitrile, apparent correlations are found between and the rate at which the plasma polymer is deposited on the substrate [2], as depicted in Figure 11.3. The effect of copolymerization of N2 and water with acetylene on the internal stress is shown in Figures 11.4 and 11.5. The copolymerization with a non-polymer-forming gas decreases the deposition rate. These figures merely indicate that the internal stress in plasma polymers prepared by radio frequency discharge varies with many factors. The apparent correlation to the parameter plotted could be misleading because these parameters do not necessarily represent the key operational parameter. 

Because of the broad scope of direct biomass pyrolysis, the basic technologies and principal products are tabulated in Table 8.12 to facilitate easy comparison. The conversion conditions and major products shown in this table are typical, but subject to considerable variation. There are several commonalities among the different pyrolysis methods. Pyrolysis time and temperature are clearly the key operating parameters that have the most influence on product yields and distributions. Moderate but optimized temperatures are needed at short residence times to maximize liquid yields, whereas long residence times and... 

In addition to its high dissolution efficiency, another powerful aspect to SFE is its ability to precisely control which component(s) of a complex matrix are extracted and which ones are left behind. This is accomplished through precise control of several key operating parameters such as temperature, pressure, flow rates, and processing time. Yields are much greater with SFE than extractions performed by traditional techniques, and product purity is usually high. Decomposition of materials almost never occurs due to the relatively mild processing temperatures. 

In conclusion it can be said that the key operating parameters to approach the ideal Knudsen separation factor (determined by mass ratio) in mesoporous membranes are small pore diameters low pressure ratio, adjusted to produce maximum separation relatively low pressure level and high process temperature. 

Model column B2 in Figure 6.8 using a detailed model, RadFrac. (Hint Use the results from Problem 6.1 to choose key operating parameters.) Prepare a report comparing the output when using DSTWU and RadFrac to model the distillation column. What information was needed for each How do the results compare ... 

Method development report. The report should review the method development and provide some justification for the choice of key operational parameters and choice of related compounds for purity methods. 

The key operational parameters for DTA (or DSC), as given by Sarasohn (84), are shown in Table 5.7. If a large sample size is chosen, lower heating rates are required. This in turn decreases the AT sensitivity and peak resolution. Small samples are perhaps the most convenient to use, especially with... 

The key operational parameters of exciplex and excimer lasers used in optical lithographic applications include exposure-dose-related parameters comprising average power, pulse energy, repetition rate, and pulse width temporal coherence spatial coherence including beam dimensions, beam divergence, and beam uniformity and maintenance and reliability. Table 13.2 lists some of the key operational parameters of KrF, ArF, and F2 laser systems used in optical lithography. 

For each element of the infrastructure, technical specifications should detail what is to be installed, the purpose of the element being installed, the key operating parameters, the interfaces to other infrastructure and the key constraints of the system. These documents, which may include drawings, diagrams and some supplier documentation, must be reviewed, approved, formally controlled and kept up to date. 

A key operating parameter is pressure drop across the pipeline, for which a knowledge of the emulsion s rheological properties is needed. Although use may be made of batch rheological measurements (Section 6.2), the final data for scale-up are usually obtained from viscosities determined in a pilot plant, involving large batches of the prospective emulsion that are made to flow in a pipeline loop. 

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