A NIR-Based Study of Desorption Kinetics during Continuous Spin Freeze-Drying

The pharmaceutical industry is progressing toward the development of more continuous manufacturing techniques. At the same time, the industry is striving toward more process understanding and improved process control, which requires the implementation of process analytical technology tools (PAT). For the purpose of drying biopharmaceuticals, a continuous spin freeze-drying technology for unit doses was developed, which is based on creating thin layers of product by spinning the solution during the freezing step. Drying is performed under vacuum using infrared heaters to provide energy for the sublimation process. This approach reduces drying times by more than 90% compared to conventional batch freeze-drying. In this work, a new methodology is presented using near-infrared (NIR) spectroscopy to study the desorption kinetics during the secondary drying step of the continuous spin freeze-drying process. An inline PLS-based NIR calibration model to predict the residual moisture content of a standard formulation (i.e., 10% sucrose) was constructed and validated. This model was then used to evaluate the effect of different process parameters on the desorption rate. Product temperature, which was controlled by a PID feedback mechanism of the IR heaters, had the highest positive impact on the drying rate during secondary drying. Using a higher cooling rate during spin freezing was found to significantly increase the desorption rate as well. A higher filling volume had a smaller negative effect on the drying rate while the chamber pressure during drying was found to have no significant effect in the range between 10 and 30 Pa.

Impact of the Freeze-Drying Conditions Applied to Obtain an Orange Snack on Energy Consumption

Nowadays, the consumer is looking for healthier, more attractive, ready-to-eat, and safer foodstuffs than fresh products. Despite freeze drying being known for providing high added value products, it is a slow process which is conducted at low pressures, so, in terms of energy consumption, it turns out to be quite costly for the food industry. With the purpose of obtaining a freeze-dried orange puree, previously formulated with gum Arabic and bamboo fiber, which can be offered to consumers as a snack at a low economic cost, the impact of the process conditions on energy consumption has been considered. The product temperature evolution and the energy consumption were registered during the drying of frozen samples at different combinations of chamber pressures (5 and 100 Pa) and shelf temperatures (30, 40 and 50 °C). In each case, the time processing was adapted in order to obtain a product with a water content under 5 g water/100 g product. In this study, the secondary drying stage was considered to start when the product reached the shelf temperature and both the pressure and the temperature affected the duration of primary and secondary drying stages. The results obtained led to the conclusion that the shorter duration of the process when working at 50 °C results in significant energy saving. Working at a lower pressure also contributes to a shortening of the drying time, thus reducing the energy consumption: the lower the temperature, the more marked the effect of the pressure.

FEATURES OF THE DEVELOPMENT OF A LYOPHILIZED INJECTABLE DOSAGE FORM OF THE ORIGINAL ANTICANCER DRUG LCS-1208

Objective: Development of a lyophilized injectable dosage form LCS-1208, an original antitumor drug based on an indolocarbazole derivative. Methods: The prepared solution of the injectable dosage form LCS-1208 is transferred to sterilizing filtration, which is carried out under vacuum on a «Stericup» filter unit with a filter pore size of 0.22 μm. The sterile solution of the injectable dosage form LCS-1208 is poured into sterile vials using a dispenser and lyophilized in a freeze-drying chamber. At the end of drying, the preparation is corked in the chamber of a sublimation unit using a hydraulic device and transferred to crimping with aluminum caps using a seaming machine. Quantitative determination of the drug content was determined by spectrophotometry using a standard sample at λ = 320±2 nm. The pH was determined by potentiometry. Results: A freeze-drying regimen for the injectable dosage form LCS-1208 has been developed. The required solution freezing temperature was established taking into account the presence of 2 eutectic zones: a solution of LCS-1208 in DMSO (-35 ÷-32) °С, an aqueous solution of Kollidon 17PF (-10 ÷-8) °С. As a result of a series of experiments, the optimal lyophilization regime was chosen that does not require preliminary freezing in a low-temperature chamber, with freezing on the shelves of freeze-drying at a temperature of-47 °C without their preliminary cooling. The most acceptable vial filling volume was determined, amounting to 3 ml, and the rate of temperature rise during secondary drying of the preparation was justified. When using the developed regime of lyophilization of the LCS-1208 solution, it was shown that it can be sublimated while preserving the initial qualitative and quantitative characteristics. Conclusion: In this article, using the example of creating a lyophilized injectable dosage form LCS-1208 (the original antitumor drug from the indolocarbazole group), the main problems that arose during the lyophilization of the selected composition of the model solution, as well as ways to improve the process.

The Freeze-Drying of Foods—The Characteristic of the Process Course and the Effect of Its Parameters on the Physical Properties of Food Materials

Freeze-drying, also known as lyophilization, is a process in which water in the form of ice under low pressure is removed from a material by sublimation. This process has found many applications for the production of high quality food and pharmaceuticals. The main steps of the freeze-drying process, such as the freezing of the product and primary and secondary drying, are described in this paper. The problems and mechanisms of each step of the freeze-drying process are also analyzed. The methods necessary for the selection of the primary and secondary end processes are characterized. The review contains a description of the effects of process conditions and the selected physical properties of freeze-dried materials, such as structural properties (shrinkage and density porosity), color, and texture. The study shows that little attention is given to the mechanical properties and texture of freeze-dried materials obtained from different conditions of the lyophilization process.

Solvent-Assisted Secondary Drying of Spray-Dried Polymers

Purpose The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spray-drying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spray-drying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas. The product dries rapidly to form a powder, but small amounts of residual solvent (typically, 1 to 10 wt%) remain in the product and must be removed in a secondary-drying process. For some spray-dried materials, secondary drying by traditional techniques can take days and requires balancing stability risks with process time. Methods Spray-dried polymers were secondary dried, comparing the results for three state-of-the-art methods that employed a jacketed, agitated-vessel dryer: (1) vacuum-only drying, (2) water-assisted drying, or (3) methanol-assisted drying. Samples of material were pulled at various time points and analyzed by gas chromatography (GC) and Karl Fischer (KF) titration to track the drying process. Results Model systems were chosen for which secondary drying is slow. For all cases studied, methanol-assisted drying outperformed the vacuum-only and water-assisted drying methods. Conclusions The observation that methanol-assisted drying is more effective than the other drying techniques is consistent with the free-volume theory of solvent diffusion in polymers.

Pemanfaatan panas kondenser pada pengering beku vakum

Pengering beku vakum (Freeze vacuum drying) merupakan salah satu metode pengeringan terbaik untuk pengawetan bahan makanan. Selain menjadi salah satu solusi untuk teknologi pasca panen, freeze vacuum drying juga mampu untuk meningkatkan nilai jual suatu produk. Penelitian ini bertujuan untuk mengembangkan pengering beku vakum yang menggunakan sistem pemanasan mandiri (self heating system) dengan pemanfaatan panas kondenser. Pada awal penelitian tanpa proses secondary drying dibutuhkan waktu 24 jam untuk menghilangkan kadar air sebanyak 62% dari produk dengan temperature -5oC. Penelitian berikutnya dengan memanfaatkan panas buang kondenser dan menggunakan proses secondary drying dibutuhkan waktu 4 jam untuk mengurangi kadar air pada produk sebesar 78% pada temperature -9oC. Freeze vacuum drying is one of the best drying methods for food preservation. Besides being one of the solutions for post-harvest technology, freeze vacuum drying is also able to increase the sale value of a product. The aim of this research is to develop a freeze vacuum drying using a self-heating system by utilizing a heat of condenser. At the beginning of the research without secondary drying process, it took 24 hours to remove 62% of water content from products with a temperature of -5oC. In further research by utilized waste heat of condenser and by using secondary drying process, it took 4 hour to reduce 78% moisture content of product at -9oC.