Development and validation of an HPLC method for the determination of process-related impurities in pridinol mesylate, employing experimental designs

A simple high performance liquid chromatographic method for the determination of process-related impurities in bulk drug of the central anticholinergic compound pridinol mesylate, has been developed and validated. Spectroscopically characterized synthetic impurities were used as standards. The chromatographic separation was optimized employing an experimental design strategy, and was achieved on a C₁₈ column with a mobile phase containing 50 mM potassium phosphate buffer (pH 6.4), MeOH and 2-propanol (20:69:11, v/v/v), delivered at a flow rate of 1.0 mL min⁻¹. UV detection was performed at 245 nm. The optimized method was thoroughly validated, demonstrating to be selective, when the chromatogram was recorded with a diode-array detector and peak purities were evaluated (>0.9995). The method is robust and linear (r² > 0.99) over the range 0.05-2.5% (5-250% with regards to the 1% specification limit for both process-related impurities); it is also precise, regarding repeatability (RSD ≤ 1.5% for all of the analytes) and intermediate precision aspects and LOQ values for the impurities are below 0.01%. Method accuracy, evidenced by low bias of the results and analyte recoveries in the range of 99.1-102.7%, was assessed at five analyte concentration levels. The usefulness of the determination was also demonstrated through the analysis of different lots of pridinol mesylate bulk substance. The results indicate that the method is suitable for the quality control of the bulk manufacturing of pridinol mesylate drug substance.     

Rapid and modular prototyping-based Petri nets and distributed simulation for manufacturing systems

This paper presents an approach to simulate and implement by stepwise refinement the whole manufacturing system (MS) by means of distributed simulation. This approach is based on the use of different classes of Petri nets to model different levels of a manufacturing system. Furthermore these classes may match the abstraction levels of a high-level Petri net used to model the MS. Each level can be simulated on a processor or a cluster of processors which can communicate between themselves using a network. The main contribution is to give the opportunity to combine simulation, performance evaluation and emulation. The emulation means that a part of the system can be run in real time while the other part is simulated. Moreover based on the abstraction levels of high-level Petri nets, subsystems can be integrated step-by-step from the design stage to the implementation one, allowing inter-changeability between simulated components and real-time physical systems. This approach is achieved by defining a simulation engine which involves a local simulator, an emulator and an interface to the physical process. Criteria are defined to use an emulator or a local control software for a physical process as a logical process for the conservative distributed simulation.     

Maintenance scheduling of a protection system subject to imperfect inspection and replacement

An inspection and replacement policy for a protection system is described in which the inspection process is subject to error, and false positives (false alarms) and false negatives are possible. We develop two models: one in which a false positive implies renewal of the protection system; the other not. These models are motivated by inspection of a protection system on the production line of a beverage manufacturer. False negatives reduce the efficiency of inspection. Another notion of imperfect maintenance is also modelled: that of poor installation of a component at replacement. These different aspects of maintenance quality interact: false alarms can, in a worst case scenario, lead to the systematic and unnecessary replacement of good components by poor components, thus reducing the availability of the system. The models also allow situations in which maintenance quality differs between alternative maintainers to be investigated.     

A hybrid optimization approach for multi-level capacitated lot-sizing problems

Solving multi-level capacitated lot-sizing problems is still a challenging task, in spite of increasing computational power and faster algorithms. In this paper a new approach combining an ant-based algorithm with an exact solver for (mixed-integer) linear programs is presented. A MAX–MIN ant system is developed to determine the principal production decisions, a LP/MIP solver is used to calculate the corresponding production quantities and inventory levels. Two different local search methods and an improvement strategy based on reduced mixed-integer problems are developed and integrated into the ant algorithm. This hybrid approach provides superior results for small and medium-sized problems in comparison to the existing approaches in the literature. For large-scale problems the performance of this method is among the best.     

A hybrid fuzzy integral decision-making model for locating manufacturing centers in China: A case study

This study presents a hybrid fuzzy integral decision-making model that integrates factor analysis, interpretive structural modeling, Markov chain, fuzzy integral and the simple additive weighted method for selecting locations of high-tech manufacturing centers in China. The analytical results of this case study demonstrate the feasibility of the proposed model for solving fuzzy multiple attribute decision-making problems, especially when criteria are interdependent. Further, the empirical study brings out some properties that are crucial for high-tech manufacturing centers to invest in China.     

Evaluating the suitability of acoustical measurement techniques and psychophysical testing for studying the consistency of musical wind instrument manufacturing

Musicians often claim to be able to discern differences in the playing properties of musical wind instruments that have been manufactured in exactly the same way. These differences are most likely due to disparities in bore profile or in the positioning and sealing of any valves or side holes. In this paper, the suitability of acoustic pulse reflectometry and a capillary-based impedance measurement technique for detecting differences between instruments of the same model is explored through measurements on two low-cost, mass-produced trumpets. Differences in the measured bore profiles of the two instruments are reported, with the largest deviation caused by the presence of a leak in the third valve of one of the trumpets. Differences in input impedance measurements made on the two instruments are also noted, with the main cause shown to be the leaky valve. Controlled playing tests are carried out using the same two trumpets in order to evaluate the effectiveness of psychophysical testing in establishing whether there are perceptible differences in the playing properties of nominally identical wind instruments. A semi-professional musician is proved to be able to discriminate between the trumpets whereas an amateur player is shown to be unable to do the same.     

Age-dependent production planning and maintenance strategies in unreliable manufacturing systems with lost sale

In this paper, we formulate an analytical model for the joint determination of an optimal age-dependent buffer inventory and preventive maintenance policy in a production environment that is subject to random machine breakdowns. Traditional preventive maintenance policies, such as age and periodic replacements, are usually studied based on simplified and non-realistic assumptions, as well as on the expected costs criterion. Finished goods inventories and the age-dependent likelihood of machine breakdowns are usually not considered. As a result, these policies could significantly extend beyond the anticipated financial incomes of the system, and lead to crises. In order to solve this problem, a more realistic analysis model is proposed in this paper to consider the effects of both preventive maintenance policies and machine age on optimal safety stock levels. Hence, a unified framework is developed, allowing production and preventive maintenance to be jointly considered. We use an age-dependent optimization model based on the minimization of an overall cost function, including inventory holdings, lost sales, preventive and corrective maintenance costs. We provide optimality conditions for the manufacturing systems considered, and use numerical methods to obtain an optimal preventive maintenance policy and the relevant age-dependent threshold level production policy. In this work, this policy is called the multiple threshold levels hedging point policy. We include numerical examples and sensitivity analyses to illustrate the importance and the effectiveness of the proposed methodology. Compared with other available optimal production and maintenance policies, the numerical solution obtained shows that the proposed age-dependent optimal production and maintenance policies significantly reduce the overall cost incurred.     

Improved formulation,branch-and-cut and tabu search heuristic for single loop material flow system design

The single loop material flow system design is a combinatorial optimization problem, arising in material handling system design, which amounts to designing an unidirectional loop flow pattern as well as to locate pickup and delivery stations. The objective is to minimize the time required to carry out all material flow movements between cells. In this paper, we develop valid inequalities for a previously proposed formulation. The valid inequalities are then embedded into a branch-and-cut framework which is shown to solve much larger instances to optimality than those reported in the literature. A tailored tabu search heuristic is also illustrated and computationally assessed.     

A bi-objective coordination setup problem in a two-stage production system

This paper addresses a problem arising in the coordination between two consecutive departments of a production system, where parts are processed in batches, and each batch is characterized by two distinct attributes. Due to the lack of interstage buffering between the two stages, these departments have to follow the same batch sequence. In the first department, a setup occurs every time the first attribute of a new batch is different from the one of the previous batch. In the downstream department, there is a setup when the second attribute changes in two consecutive batches. The problem consists in finding a batch sequence optimizing the number of setups paid by each department. This case results in a particular bi-objective combinatorial optimization problem. We present a geometrical characterization for the feasible solution set of the problem, and we propose three effective heuristics, as shown by an extensive experimental campaign. The proposed approach can be also used to solve a class of single-objective problems, in which setup costs in the two departments are general increasing functions of the number of setups.     

An attribute approach to the measurement of machine-group flexibility

Researchers have emphasized that different factors have to be considered when discussing the flexibility of a single machine and that of a group of machines. The present research focuses on proposing methods for measuring machine-group flexibility, which is an extension of the model for measuring single machine flexibility. The measurement of machine-group flexibility needs to take into account at least the following three attributes, namely efficiency, versatility and redundancy. Measurement models for each of these three attributes are demonstrated, and a combined measurement approach for machine-group flexibility is suggested. The entropy approach, which states that the greater the number of available options, the larger the entropy value, is applied to the measurement of versatility and redundancy. Finally, an example illustrates the application of the flexibility measurement models developed in this research.