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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

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

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

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

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

Membrane‐Freeze Concentration Hybrid for Temperature‐Sensitive Biomolecules. Investigation, Application, and Techno‐Economic Benefits

Timo van Beek, Michael Budde, Jan van Esch

Abstract

In order to close the technology gap between membrane technologies and spray/freeze‐drying ideally with a technology that avoids thermal stress to sensitive enzyme solutions, the limits of freeze concentration for this application have been investigated. On laboratory scale it was found that average crystal sizes are > 300 µm despite high viscosity and ice separation is possible up to 42 % solids and > 1000 mm2s−1 viscosity. No activity loss was observed during concentration. A combination of two‐stage freeze concentration with a filter and wash column for ice liquid separation in an integrated setup with ultrafiltration has the greatest potential and was shown to be economically feasible in three out of four cases studied.

Keywords

Biomolecules, Crystal size, Freeze concentration, Freeze‐drying, Membrane separation, Sensitive enzymes

How different nanoparticles affect the rheological properties of aqueous Wyoming sodium bentonite suspensions

Abstract

Clay suspensions present complex microstructures in different environments and deep understanding of such microstructures is crucial to control their flow properties. Their rheological profile is closely linked with the structural association (3-D network) of bentonite particles. Nanomaterials are considered very good candidates for smart fluids formulation which can improve the performance of conventional drilling fluids. Their incorporation in water-bentonite suspensions endow complex microstructures and hence complex rheological behavior, which is still under investigation. This study aims to explore the micro-mechanisms involved on shaping this rheological behavior with samples of 7 wt% water-sodium bentonite suspensions containing 0.5 wt% each of, commercial Fe3O4, commercial SiO2 NP and custom-made (bare or citric acid coated) Fe3O4 NP at alkaline pH. We tried to achieve this by combining macroscopic measurements (rheological measurements) with microscopic measurements (i.e. TEM). A comprehensive physico-chemical characterization of the materials and suspensions was performed using X-Ray Diffraction (XRD), X-Ray Fluorescence (XRF), N2 adsorption-desorption isotherms and Fourier-transform infrared spectroscopy (FTIR). An effective drying process was adopted using freeze-granulation and freeze-drying (FG-FD) techniques in order to capture as accurately as possible the evolved microstructures of these aqueous bentonite suspensions at the different temperatures (25–60 °C). The results indicated that all samples exhibited a yield stress followed by a shear thinning behavior. The three parameter Herschel-Bulkley model provided excellent fit of the experimental data for all samples. HR-TEM images revealed that the association of the nanoparticles with bentonite particles in different configurations plays a crucial role in their rheological characteristics with the charge and the coating of the added nanoparticles being important factors in determining the magnitude of the effects observed. We hypothesize that attractive magnetic forces between the magnetite nanoparticles may suppress the electrostatic repulsions and thus they may play a key role in promoting the observed aggregation of the nanoparticles which in turn plausibly affected their rheological profile. A thorough examination and understanding of the evolution of such complex inter-particle structures may lead towards an optimal rheology control of such suspensions in a wide range of applications.

Effect of porous structure and spreading pressure on the storage stability of red onion microcapsules produced by spray freezing into liquid cryogenic and spray drying

L.A. Pascual-Pineda, M.P. Rascón, M.X. Quintanilla-Carvajal, M. Castillo-Morales, U.R. Marín, E. Flores-Andrade

Abstract

Red onion microcapsules were produced by spray freezing into liquid cryogenic (SFLC) and spray drying (SD) and their anthocyanin contents were evaluated kinetically at different water activities () at 35 °C. The spreading pressure-area isotherms were determined at 35 °C. These isotherms provide important information about the different phases of adsorbed water present in SD and SFLC capsules, which can be related to minimal integral entropy and to chemical stability during storage. The porosity of the microcapsules was examined using low-temperature adsorption of nitrogen. The maximum anthocyanin stability occurred at from 0.108 to 0.318, and 0.108 to 0.515, for SD and SFLC, respectively. SD products were nonporous whereas SFLC were mesoporous. The tendency to contraction of the adsorbed water film was compared with the minimum integral entropy and was proposed as a new stability criterion to predict suitable storage conditions of dehydrated foods.

Keywords

Minimum integral entropy, Monolayer, Spreading pressure, Spray freezing into liquid nitrogen

Freeze Granulation for the Processing of Silicon Nitride Ceramics

Ola Lyckfeldt, Kent Rundgren, M. Sjöstedt

Abstract

Freeze granulation (LS-2, PowderPro HB, Sweden) has been demonstrated as a favourable alternative to conventional granulation methods (spray drying, sieve granulation etc) in the production of granules for the pressing of high-performance ceramic powders. Freeze granulation/freeze drying prevents the migration of pressing aids or particle fines to the granule surface, as is the case in spray drying. This ensures granule homogeneity and an easy breakdown of granules during pressing. This, in turn, results in defect minimisation and optimal conditions for the sintering and the development of the desired material properties. In this study silicon nitride materials have been produced using freeze granulation, pressing and sintering to validate the performance. Materials with competitive properties were manufactured based on medium-cost, direct-nitrided powders (SicoNide P95, Permascand AB, Sweden), various pressing and sintering aid compositions as well as various pressing and sintering schedules. MgO vs Fe2O3 as sintering aid, PEG vs PVA as binder and higher pressure at the initial uniaxial pressing were found to promote the sintering performance.

Selective Oxidation of HMF via Catalytic and Photocatalytic Processes Using Metal-Supported Catalysts

Lolli A, Maslova V, Bonincontro D, Basile F, Ortelli S, Albonetti S

Abstract

In this study, 5-hydroxymethylfurfural (HMF) oxidation was carried out via both the catalytic and the photocatalytic approach. Special attention was devoted to the preparation of the TiO₂-based catalysts, since this oxide has been widely used for catalytic and photocatalytic application in alcohol oxidation reactions. Thus, in the catalytic process, the colloidal heterocoagulation of very stable sols, followed by the spray-freeze-drying (SFD) approach, was successfully applied for the preparation of nanostructured porous TiO₂-SiO₂ mixed-oxides with high surface areas. The versatility of the process made it possible to encapsulate Pt particles and use this material in the liquid-phase oxidation of HMF. The photocatalytic activity of a commercial titania and a homemade oxide prepared with the microemulsion technique was then compared. The influence of gold, base addition, and oxygen content on product distribution in the photocatalytic process was evaluated.

Keywords

5-hydroxymethyl furfural; TiO2; microemulsion; photocatalysis; spray-freeze drying