1,721,026 research outputs found
On-line monitoring of the freeze-drying process: A new image-based PAT.
Full text linkIn this work a Process Analytical Technology (PAT) for the on-line monitoring of a Vacuum Freeze-Drying (VFD) based on the information extracted from the infrared images of the process is presented and validated. An infrared camera, placed inside the drying chamber, provided information about the thermal evolution of the process over time; after images pretreatment and segmentation, temperature profiles were extracted and processed to obtain the variables of interest. Experiments were carried out according to factorial design on a set of different operating conditions, namely fluid temperature and chamber pressure, type of vials and solid percentage in the solution. Both sucrose and mannitol solutions, were studied. Together with the temperature in several positions along the product height, we were able to correctly estimate the ending time of the primary drying phase together with the sublimating interface position and the heat and mass transfer coefficients, Kv and Rp. Those two parameters have a dramatic importance since they can be used in a mathematical model of the process for on-line or off-line optimization of the process. Being based on a contactless technology, the PAT studied in this work does not present any issue regarding the sterility requirement of the process or the possible interference of the sensing element with the product dynamics
Temperature/end point monitoring and modelling of a batch freeze-drying process using an infrared camera
Full text linkTemperature monitoring and accurate drying end time determination are crucial for final product quality in vacuum freeze-drying of pharmaceuticals. Whether crystalline or amorphous solutes are used in the formulation, product temperature during ice sublimation should be kept below a threshold limit to avoid damage to the product structure. Hence, there is a need to continuously monitor product temperature throughout the process. Current monitoring tools, such as thermocouples and Pirani gauge pressure sensors, have several limitations such as affecting product dynamics or imprecise end point determination. In this work, a monitoring tool based on infrared (IR) thermography is used for batch freeze-drying processes. Batches using three different vial sizes, with up to 157 vials, were studied, allowing to extend and better describe the representativeness of IR thermography for this application. The detailed axial temperature profiles obtained through IR imaging allowed not only a comprehensive non-invasive temperature monitoring of the product, but also tracking of the sublimation interface. IR temperature measurements and primary drying end point determination were compared to standard methods and thus verified. Parameters important for freeze drying design space calculation, namely the global heat coefficient (K_v) and cake resistance to vapor flow (R_p), were also accurately estimated with the proposed method
Application of multivariate image analysis to thermal images for on-line monitoring of the freeze-drying process
Full text link[EN] A new Process Analytical Technology (PAT) has been developed and tested for on-line process monitoring of a vacuum freeze-drying process. The sensor uses an infrared camera to obtain thermal images of the ongoing process and multivariate image analysis (MIA) to extract the information after automatic detection and segmentation of the region corresponding to the product in every vial. A reference model was built, using the information of six batches, and different kind of anomalous events, involving either single vials in the batch or the whole batch, were simulated to test the capacity of the MIA-based monitoring system to promptly identify them.Colucci, D.; Prats-Montalban, J.; Fissore, D.; Ferrer Riquelme, A. (2018). Application of Multivariate Image Analysis to Thermal Images for in line Monitoring of the Freeze-Drying Process. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 163-170. https://doi.org/10.4995/IDS2018.2018.7558OCS16317
Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes
Full text linkPurpose: Present (i) an infrared (IR)-based Process Analytical Technology (PAT) installed in a lab-scale freeze-dryer and (ii) a micro freeze-dryer (MicroFD®) as effective tools for freeze-drying design space calculation of the primary drying stage. Methods: The case studies investigated are the freeze-drying of a crystalline (5% mannitol) and of an amorphous (5% sucrose) solution processed in 6R vials. The heat (Kv) and the mass (Rp) transfer coefficients were estimated: tests at 8, 13 and 26 Pa were carried out to assess the chamber pressure effect on Kv. The design space of the primary drying stage was calculated using these parameters and a well-established model-based approach. The results obtained using the proposed tools were compared to the ones in case Kv and Rp were estimated in a lab-scale unit through gravimetric tests and a thermocouple-based method, respectively. Results: The IR-based method allows a non-gravimetric estimation of the Kv values while with the micro freeze-dryer gravimetric tests require a very small number of vials. In both cases, the obtained values of Kv and Rp, as well as the resulting design spaces, were all in very good agreement with those obtained in a lab-scale unit through the gravimetric tests (Kv) and the thermocouple-based method (Rp). Conclusions: The proposed tools can be effectively used for design space calculation in substitution of other well-spread methods. Their advantages are mainly the less laborious Kv estimation process and, as far as the MicroFD® is concerned, the possibility of saving time and formulation material when evaluating Rp
On the roboustness of the soft-sensors used to monitor a vial freeze-drying process
No full textProcess monitoring is a key issue in pharmaceutical freeze-drying to evaluate if the limit product temperature is approached, to identify the ending point of the main drying stage, and to estimate the value of some parameters of a mathematical model of the process so that it can be used for cycle optimization. Soft sensors can be used for this purpose: three algorithms, based on the extended Kalman filter and on product temperature measurement, have been compared in this study; they differ on the number of estimated parameters and on the way used to set their initial estimates. Results evidence that the accuracy of estimates is strongly dependent on the initial values of model parameters, and soft sensors #1 and #2 require a preliminary investigation to get accurate initial estimates of the heat and mass transfer coefficients. Soft sensor #2 should be preferred as it just requires an initial estimate of the heat transfer coefficient. Significant advantages are obtained with soft sensor #3: accurate estimates are obtained whichever values of the parameters are used to start the calculations (provided that reasonable values are used) and,
thus, it can be effectively used to monitor the freeze-drying cycle without any preliminary investigation. Soft sensor #3 should thus be preferred to the other tools for freeze-drying monitoring
Freeze Drying of Pharmaceutical Products
Full text linkFreeze Drying of Pharmaceutical Products provides an overview of the most recent and cutting-edge developments and technologies in the field, focusing on formulation developments and process monitoring and considering new technologies for process development.
This book contains case studies from freeze dryer manufacturers and pharmaceutical companies for readers in industry and academia. It was contributed to by lyophilization experts to create a detailed analysis of the subject matter, organically presenting recent advancements in freeze-drying research and technology. It discusses formulation design, process optimization and control, new PAT-monitoring tools, multivariate image analysis, process scale-down and development using small-scale freeze-dryers, use of CFD for equipment design, and development of continuous processes
NIR-based real-time monitoring of freeze-drying processes: Application to fault and endpoint detection
Full text linkIn the pharmaceutical industry, freeze-drying is crucial for the stability of active pharmaceutical ingredients (APIs). Monitoring this complex process presents challenges as traditional methods often lack real-time insights, potentially leading to quality issues and batch rejections. Effective monitoring is then essential for optimizing process parameters and minimizing waste, thus saving costs and resources. This study evaluated the application of Near-Infrared (NIR) spectroscopy for the real-time monitoring of the freeze-drying process: NIR spectra were acquired in-line via a specially designed flange in the freeze-dryer. Two approaches were investigated. The first involved freeze-drying monitoring using control charts, thus creating a reference model based on cycles under normal
conditions. A PCA model was developed using these reference cycles, and an intentional fault cycle was performed to test the system’s ability to detect deviations. Multivariate control charts, utilizing Hotelling’s T2 and DModX metrics, were shown to effectively monitor process deviations, enhancing the understanding of freeze-drying dynamics. The second approach was based on the use of NIR spectroscopy for assessing residual moisture during lyophilization. By integrating Partial Least Squares (PLS) regression with inline NIR spectra, we estimated endpoints and detected faults in both reference and faulty cycles. The results showed strong correlations between PLS estimates and the Pirani–Baratron method, highlighting NIR’s applicability for monitoring drying phases. This research
advocates for broader NIR implementation in pharmaceutical development, emphasizing its potential to monitor the process, ensure quality, and reduce out-of-specification product
Monitoring of a vial freeze-drying process with IR thermography.
Full text linkThis work presents a new device constituted by an IR camera placed inside the drying chamber to monitor the temperature of the vials without interferences. It is possible to estimate the ending point of the primary drying, the heat transfer coefficient to the product and the resistance of the dried product to vapor flux. Experiments were performed in a freeze-dryer using thermocouples and the IR camera. The measurements validate the IR camera as an effective technology for the process
Risk assessment in freeze-drying processes
Full text linkThe risks identification is a key step for the safe design of a manufacturing process and, in this framework, once the threats to the process have been pointed out, it is important to evaluate their consequences, as well as their causes. In this paper, the risk assessment has been used to build the basis for the risk-based decision making in plant and process design of a pilot scale freeze-dryer, to be then exploited in the design of a full scale safer plant, taking into account also the experimental evaluation of possible human errors
- …
