Non-Invasive Temperature Monitoring in Freeze Drying: Control of Freezing as a Case Study

In this study, a new technology, based on the use of an array of thin-film thermocouples, is proposed for the real-time and non-invasive monitoring of product temperature during a freeze-drying cycle. This array of thin-film thermocouples was demonstrated to give quantitative accurate results without altering the freezing and drying behavior of the monitored vials, making this sensor a good alternative to conventional wire thermocouples. Furthermore, unlike conventional thermocouples, the array of thin-film thermocouples can measure the entire temperature profile within the product being dried and can also measure the position of the interface of sublimation. This information was then used to estimate the heat and mass transfer coefficient of the system under investigation, showing a fairly good agreement with data obtained by conventional, time-consuming procedures. Finally, it is shown how these parameters can be used to guide the lyophilization professional during the cycle development.     

Robust control of a reverse-flow reactor

This paper is focused on the design of a robust controller for a catalytic fixed-bed reactor with periodical inversion of the flow direction (reverse-flow reactor, RFR). The analogy between the RFR operated at infinite switching frequency and the countercurrent reactor is the basis of the simplified mathematical model of the reactor.The control system uses dilution and internal electric heating to ensure complete conversion of the reactants and to prevent overheating of the catalyst. As the state of the system is not fully available, apart from some temperature measurements, an observer is designed and used in the control algorithm. This is a typical case of nonlinear system with uncertainties. Following the procedure described in detail by Fissore [2008. Robust control in presence of parametric uncertainties: observer-based feedback controller design. Chemical Engineering Science, in press, doi:10.1016/j.ces.2007.12.019.], the extended model for the process is setup, thus taking into account all the simplifications of the model and linking performance and robustness to the control law, which is a simple state feedback. Simulations with randomly varying feeding concentration have been carried out in order to demonstrate the effectiveness of the proposed control system.     

Investigation of soot formation in turbulent flames with a pseudo-bivariate population balance model

Soot inception and subsequent aggregation, surface growth and oxidation are described through a new pseudo-bivariate population balance model solved with the direct quadrature method of moments (DQMOM) and implemented in a commercial computational fluid dynamics (CFD) code. This modelling strategy, that in this work is presented in its Reynolds-averaged Navier-Stokes (RANS) equation formulation, has the advantage, over conventional approaches based on the solution of a single transport equation for the soot volume fraction, to overcome the assumption of mono-dispersed soot particle size distribution. On the contrary the pseudo-bivariate approach presented in this work is able to represent the evolution of the soot particle size distribution with good accuracy and affordable computational costs, especially when compared with other multi-variate formulations previously developed. This new pseudo-bivariate model is firstly formulated and presented, then predictions obtained with different soot inception models are compared with some recent experimental data from the literature and the role played by the different phenomena involved (e.g., turbulence, oxidation and radiation) is investigated.     

Statistical reflections of researchers and their subjects.

Reviews the book, Cognition as intuitive statistics by Gerd Gigerenzer and David J. Murray (1987). The main thesis of the work is that the statistical tools that we use as researchers to evaluate the data that we collect have become projected into our subjects as models of their minds. The authors take an historical perspective to evaluate this hypothesis. They trace the development of inferential statistical methods as well as their use by experimental psychologists and concurrently trace the development of theories of how the subject's mind uses these same inferential statistical procedures to make decisions. The authors find that the latter theories supervene on the development of the earlier tools. Overall, this book provides psychologists with an opportunity to view their own irrationalities in a self-critical way not typically available in our profession. The book provides a fine critical, historical survey of how one tool--statistics--came to dominate our thinking so that it biases our theoretical perspective. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scale-up and Process Transfer of Freeze-Drying Recipes

This paper proposes a simple and effective methodology for the scale-up and process transfer of freeze-drying recipes. Process modeling allows the study of the silico product evolution in a given freeze-dryer, and calculation of the operating conditions that result in the same product dynamics in different equipment. Few experiments are necessary to determine model parameters and to characterize the two freeze-dryers. The problem of the batch non-uniformity and the effect of the parameters' uncertainty are also addressed. The effectiveness of this approach is demonstrated by means of various examples.     

Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home

PURPOSE: The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine. PATIENTS AND METHODS: A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals. RESULTS: differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups. CONCLUSION: Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.     

Selective interference in memory: The imagery-repetition effect revisited.

In a continuous paired-associate learning task, 16 undergraduates utilized rote-repetition and integrative imagery encoding strategies on a trial-by-trial basis. Each imagery or repetition study item was followed by 0-4 imagery or repetition items before test. Error data showed high performance for both imagery and repetition items with imagery interpolated activity. Further, repetition interpolated activity reduced performance for both imagery and repetition encoded items, although this effect was more pronounced for repetition items. K. N. Clayton and M. W. Warren's (1976) model of retroactive interference was used to provide a theoretical framework for interpreting these results. With either a visual or dual coding interpretation of integrative imagery, greater modality-specific interference was found for repetition in contrast to imaginal coding. The differences in original learning and in nonspecific interference for these 2 strategies were small by comparison. Thus, the difference in modality-specific interference presumably forms the basis of the imagery-repetition effect. (French summary) (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In-line control of the lyophilization process. A gentle PAT approach using software sensors

A lyophilization process is usually only specified in terms of a ‘recipe’ (shelf temperature and chamber pressure vs. time); according to the recent PAT guidelines issued by FDA, there is the need to develop in-line tools to enable better monitoring and control freeze-drying. In this work an advanced Manometric Temperature Measurement approach, called DPE (Dynamic Parameters Estimation) is first presented, based on a detailed mathematical model. In alternative, the “smart vial” concept is proposed, a Kalman filter based observer allowing an almost continuous monitoring without probes physically inserted into the product. Results obtained for pharmaceutical products in vial in a small industrial prototype equipped with the DPE-based LyoDriver control software, are presented. The software is capable to determine the optimal shelf temperature for primary drying, ensuring the fastest drying time without overcoming the maximum allowable product temperature both in scouting and production cycles. Finally, the two complementary monitoring systems, the DPE and the “smart vial”, are combined in an even more robust hybrid control system.