Fabrication of homogenous pellets by freeze granulation of optimized TiO2-Y2O3 suspensions

Fabrication of homogenous pellets by freeze granulation of optimized TiO2-Y2O3 suspensions

F. La Lumia, L. Ramond, C. Pagnoux, G. Bernard-Granger

Abstract

MOX fuels are used in nuclear reactors. To ensure the manufacture of MOX, wet processes are investigated. Freeze granulation of water-based powder suspension seems a promising way to yield homogenous and easy-to-press UO2-PuO2 granules. These granules are expected to form dense and homogenous pellets by uniaxial pressing. Granules and pellet properties are affected by suspension formulation and atomization conditions. Therefore, these conditions must be studied and optimized to produce granules with good processability and thus MOX pellets with compliant density, homogeneity and absence of defects. In this scope, key properties of water-based suspensions of UO2 and PuO2 surrogate powders, TiO2 and Y2O3 respectively, were firstly studied to assess their suitability for the freeze granulation process. These properties were compared to those of UO2 and PuO2 suspensions to verify and confirm the correctness in the choice of surrogate powders. Then, the freeze granulation process itself was investigated focusing on TiO2-Y2O3 suspensions.

Keywords

Suspension, Granulation, Freeze drying, UO2, PuO2

Supporting data and methods for the multi-scale modelling of freeze-drying of microparticles in packed-beds

Supporting data and methods for the multi-scale modelling of freeze-drying of microparticles in packed-beds

Luigi C. Capozzi, Antonello A. Barresi, Roberto Pisano

Abstract

A multi-scale approach can be used to simulate the drying behavior of microparticles in packed-bed. Data outcomes from discrete element method (DEM) and computational fluid dynamics (CFD) simulations can be used to estimate some relevant product characteristics, such as the porosity, tortuosity, voids in the bed and permeability which are required by the multi scale model. Data from DEM simulations are presented, with a particular focus on the influence of the model parameters, packing characteristics and inhomogeneities (wall effect and particles segregation); computational costs and scala bility are also considered. Data on the properties of packings as modeled at the macroscale are presented with regard to the thermal conductivity of gases in the Knudsen regime and effective properties of packed-beds modeled as a pseudo-homogeneous medium. A mathematical model of the freeze-drying of single microparticles and its outcomes are first presented. Data outcomes from the mathematical model at the macroscale concerning the drying behavior of microparticles in a tray and in a vial are then presented and can be used for process design. Some further data, with detailed interpretation and discussion of the presented data, can be found in the related research data article, “A multi-scale computational framework for modelling the freeze-drying of microparticles in packed-beds” (Capozzi et al., 2019).

Keywords

Freeze-drying, Packed-bed, Lyophilization, DEM, CFD, Spray-freeze drying

Cryogenic Fabrication of Dry Powders to Enhance the Solubility of a Promising Anticancer Drug, SHetA2, for Oral Administration.

Cryogenic Fabrication of Dry Powders to Enhance the Solubility of a Promising Anticancer Drug, SHetA2, for Oral Administration.

Ibrahim M, Hatipoglu MK, Garcia-Contreras L

Abstract

SHetA2 is a novel anticancer drug with poor aqueous solubility. In formal toxicological studies, Kolliphor HS 15 was used as a solubilizing agent to increase the oral bioavailability of SHetA2. The purpose of this study was to formulate SHetA2 and Kolliphor HS 15 as solid powders to facilitate their filling in hard gelatin capsules for clinical trials. Two manufacturing processes, ultra-rapid freeze-drying (URFD) and spray freeze drying (SFD), were employed to fabricate solid powders of SHetA2-Kolliphor HS 15 and trehalose. The morphology, size, flowability, and compressibility of URFD-SHetA2 and SFD-SHetA2 powders were characterized. The crystallinity and apparent maximum solubility of SHetA2 in both powders were also determined. SFD-SHetA2 powders were spherical in shape, small, and with a wide size distribution while the URFD-SHetA2 powders were irregularly shaped and big but with a narrower distribution. DSC and XRD analyses indicated that SHetA2 was mostly amorphous in both powders. The flow of both powders was categorized as “good” (angle of repose < 35°). The uniformity of drug content in URFD-SHetA2 powders was more variable than that in SFD-SHetA2 powders. The solubility profile of SHetA2 in both powders SGF exhibited a transient supersaturation “spring effect” due to the drug’s amorphousness followed by extended supersaturation “parachute effect” at approximately 6 μg/ml for both powders compared to 0.02 ± 0.01 μg/ml for unprocessed drug. In conclusion, both URFD and SFD formed solid SHetA2 Kolliphor powders that are possible formulation candidates to be filled in hard gelatin capsules for clinical trials.

Keywords

Kolliphor HS 15; SHetA2; spray freeze drying; spring and parachute effect; ultra-rapid freeze drying

Influence of Nanoparticle Pretreatment on the Thermal, Rheological and Mechanical Properties of PLA-PBSA Nanocomposites Incorporating Cellulose Nanocrystals or Montmorillonite

Influence of Nanoparticle Pretreatment on the Thermal, Rheological and Mechanical Properties of PLA-PBSA Nanocomposites Incorporating Cellulose Nanocrystals or Montmorillonite

Wissam Abdallah, Amin Mirzadeh, Victor Tan, Musa R. Kamal

Abstract

Nanoparticles based on cellulose nanocrystals (CNC) and montmorillonite clay (MMT) were prepared using spray freeze-drying. The nanoparticles were then used as reinforcement to prepare nanocomposites with poly(lactic acid) (PLA) as the polymer matrix. The effect of spray freeze-dried CNC (SFD-CNC) and spray freeze-dried MMT (SFD-MMT) on the rheological and mechanical properties of PLA and its blends with poly(butylene succinate)-co-adipate) were investigated. An epoxy chain extender was used during preparation of the blends and nanocomposites to enhance the mechanical properties of the products. Different methods such as scanning electron microscopy, X-ray diffraction and adsorption/desorption analyses were used to characterize the prepared nanoparticles and their localization in the blends. Dynamic oscillatory shear behavior, elongational viscosity and mechanical characteristics of the nanocomposites of PLA and the blends were evaluated. The results obtained for nanocomposites filled with unmodified SFD-MMT were compared with those obtained when the filler was a commercial organically modified montmorillonite nanoclay (methyl-tallow-bis(2-hydroxyeethyl) quaternary ammonium chloride) (C30B), which was not spray freeze-dried.

Spray Freeze-Drying Technology: Enabling Flexibility of Supply Chain and Drug-Product Presentation for Biologics

Spray Freeze-Drying Technology: Enabling Flexibility of Supply Chain and Drug-Product Presentation for Biologics

Deirdre Lowe, Mehak Mehta, Geetha Govindan, Kapil Gupta

Abstract

Biopharmaceutical drug substances (DSs) and drug products (DPs) commonly are stored frozen or refrigerated to maintain stability through long-term storage, handling, and transportation (1). Temperature excursions during storage and transport can affect product quality adversely by compromising the safety and efficacy of these molecules. Thus, cold-chain management throughout the shelf life of these products is a critical component in the supply chain strategy for them.

Pharmaceutical Freeze Drying Technology 2018

Pharmaceutical Freeze Drying Technology 2018

Overview

Although an old process, pharmaceutical freeze drying is ever evolving with new trends and approaches being used for pharmaceutical formulation. In it’s 6th year, the conference will cover the most recent advances in Freeze drying technology and discuss the latest ideas in the industry. It is the perfect platform to strengthen knowledge in key principles such as PAT and QbD, whilst staying at the forefront of technological breakthroughs to adapt to growing manufacturing demands.

Gathering a room of Senior Scientists and Heads of Pharmaceutical Engineering, the 6th annual show provides an ideal forum to discuss the latest advancements in pharmaceutical lyophilisation, welcoming regulatory guidance from the NIBSC-MHRA and expertise from the likes of Sanofi, Boehringer Ingelheim, Janssen, GSK and more!

Spray-freeze-drying: A novel process for the drying of foods and bioproducts

Spray-freeze-drying: A novel process for the drying of foods and bioproducts

S. Padma Ishwarya, C. Anandharamakrishnan, Andrew G.F. Stapley

Abstract

Spray-freeze-drying (SFD) is an unconventional freeze drying technique that produces uniquely powdered products whilst still including the benefits of conventionally freeze dried products. SFD has potential applications in high value products due to its edge over other drying techniques in terms of product structure, quality, and the retention of volatiles and bioactive compounds. In cases where other drying techniques cannot provide these product attributes, SFD stands out despite the costs and complexities involved. This paper outlines the principles, methods, significant process parameters, particle morphology and quality aspects of SFD. Recent developments in this technique are reviewed including ultrasonic spray-freeze-drying, the application of computational fluid dynamics and mathematical modelling, and the incorporation of new technologies to improve product quality. In addition, the advantages, limitations and future scope for research in the field of SFD are discussed.

Comparison of Freeze and Spray Drying to Obtain Primaquine-Loaded Solid Lipid Nanoparticles

Comparison of Freeze and Spray Drying to Obtain Primaquine-Loaded Solid Lipid Nanoparticles

Owuor James, Florence Oloo, Japheth Kibet Ngetich, Mwaiwa Kivunzya

Abstract

This article describes how the spray drying and freeze drying of various nanosized Solid Lipid Nanoparticle (SLN) and the physicochemical attributes of the acquired particles were examined. Primaquine loaded Solid Lipid Nanoparticles dried by the two strategies is examined. Particles were characterised by determination of size, drug loading, encapsulation efficiency and surface morphology. In vitro and kinetic drug discharge models were also considered. Preparation parameters have no impact on the molecule morphology and properties, and the main parameter deciding the molecule attributes in the drug substance of the nanoparticle, either in the spraying or in the freezing technique of drying. The drug release profile of spray dried SLN is superior to that of the freeze dried SLN.

Thermal inactivation kinetics of microencapsulated microbial transglutaminase by ultrasonic spray-freeze drying

Thermal inactivation kinetics of microencapsulated microbial transglutaminase by ultrasonic spray-freeze drying

Hilal Isleroglu, Izzet Turker

Abstract

Partially purified microbial transglutaminase (mTG) was microencapsulated by ultrasonic spray-freeze drying (USFD) as a novel method, using a 48 kHz ultrasonic nozzle. The microencapsulated samples, which used a mixture of inulin and gum arabic as coating materials, were compared to microencapsulated samples by conventional freeze-drying (CFD) and conventional spray drying (CSD) in terms of thermal stability. Thermal inactivation kinetics of the microencapsulated and as well as crude enzymes obtained by USFD process (USFD-crude) were evaluated according to first-order reaction kinetics in the range of 40–60 °C at different pH values (5.0–7.0), and the activation energy (Ea, kJ/mol) and free energy for thermal inactivation (ΔG, kJ/mol) were calculated. Furthermore, the specific surface area (SSA, m2/g) of the samples was determined, and a relationship between SSA and thermal stability was established. The results showed that the thermal stability of microencapsulated mTG by USFD was higher than all samples, having smaller rate constants and Ea values with higher half-life times and ΔG values. In addition, the thermal stability of the samples decreased when the SSA increased, as in USFD-crude and CSD samples.

Keywords

Ultrasonic spray-freeze drying Microbial transglutaminase Thermal inactivation Microencapsulation Specific surface area

Innovative synthesis of nanostructured composite materials by a spray-freeze drying process: Efficient catalysts and photocatalysts preparation

Innovative synthesis of nanostructured composite materials by a spray-freeze drying process: Efficient catalysts and photocatalysts preparation

Alice Lolli, Magda Blosi, Simona Ortelli, Anna Luisa Costa, Ilaria Zanoni, Danilo Bonincontro, Francesca Carella, Stefania Albonetti

Abstract

The spray-freeze-drying (SFD) approach was successfully applied for the preparation of nanostructured porous mixed oxides with high surface area. The preparation of different composite materials and the encapsulation of metal nanoparticles in inorganic matrix was easily obtained using this interesting technique. In particular, TiO2-SiO2 mixed-oxides were produced at different compositions using the colloidal heterocoagulation of very stable sols, associated with SFD. Moreover, its versatility allowed the incorporation of metal. This synthetic approach led to the preparation of porous micro-granules characterised by a high homogeneity in the phase distribution. The prepared materials were active and selective in the reduction of 5-hydroxymethyl-2-furfural (HMF) to 2,5-bishydroxymethylfuran (BHMF) and in the photodegradation of rhodamine B (RhB), used as a as a stain model. These encouraging results pave the way for the use of this method for the homogeneous embedding of different typologies of catalytic active phases (metal nanoparticles, inorganic complexes, enzyme) into any kind of support (inorganic, organic, polymeric) minimizing the possibility of phase separation on a molecular scale, as also demonstrated for drugs.

Keywords

Spray-freeze-drying, Hetero-coagulation, Colloid, TiO2, SiO2