Spray Freeze Drying Research Articles

Particle Morphology of Spray-Freeze Dried Microencapsulation Agents

Spray-freeze drying (SFD) is a relatively new technique for microencapsulation of heat sensitive products. In SFD process, the solution is sprayed in a cryogenic medium such as liquid nitrogen to form frozen fine droplets. Then, the droplets subjected to freeze-drying under vacuum. The freeze-drying time is comparatively short due to the relatively large surface area achieved by the SFD. In this study, frequently used microencapsulation agents namely maltodextrin, inulin and gum arabic were spray-freeze dried both individual and in the form of mixtures and the resulting powders were characterized with respect to particle morphologies. Morphology of the particles were observed using Scanning Electron Microscopy (SEM). All the spray-freeze dried particles showed spherical shape, sometimes being slightly aggregated. Regular pore structures originating from the formation of crystals were observed on the surface of the maltodextrin particles, while the gum arabic particles were found to have more irregular and small pores. However, inulin particles were found to have a smoother surface form than others. Keywords : Spray-freeze drying, morphology, inulin, maltodextrin, gum Arabic DOI : 10.7176/JSTR/5-2-24

Bulk Dynamic Spray Freeze-Drying Part 2: Model-Based Parametric Study for Spray-Freezing Process Characterization

Spray freeze-drying is an evolving technology that combines the benefits of spray-drying and conventional lyophilization techniques to produce drug substance and drug product as free-flowing powders. The high surface-to-volume ratio associated to the submillimeter spray-frozen particles contributes to shorter drying and reconstitution times. The formation of frozen particles is the most critical part of this dehydration technique because it defines the properties of final product. Based on a previously proposed and validated model, the current goal is to understand the role of various controllable parameters in the spray-freezing process. More specifically, given a set of spraying conditions, the model is used to predict the minimum distance required to cool and freeze the droplets below a temperature that prevents coalescence and product agglomeration. A parametric study is carried out to map the operational limit conditions of the actual spray-freezing column apparatus under consideration. For the spray freeze-drying conditions of interest, model simulations indicate that convection contributes to at least 80% of the total droplet heat transfer and, consequently, that freezing column gas temperature and droplet diameter are the most important process parameters affecting the freezing distance.

Bulk Dynamic Spray Freeze-Drying Part 1: Modeling of Droplet Cooling and Phase Change

In spray freeze-drying (SFD), the solution is typically dispersed into a gaseous cold environment producing frozen microparticles that are subsequently dried via sublimation. This technology can potentially manufacture bulk lyophilized drugs at higher rates compared with conventional freeze-drying in trays and vials because small frozen particles provide larger surface area available for sublimation. Although drying in SFD still has to meet the material collapse temperature requirements, the final characteristics of the respective products are mainly controlled by the spray-freezing dynamics. In this context, the main goal of this work is to present a single droplet spray-freezing model and validate it with previously published simulations and experimental data. For the investigated conditions, the droplet temperature evolutions predicted by the model agree with experiments within an error of ±10%. The proposed engineering-level modeling framework is intended to assist future development of efficient SFD processes and support scale up from laboratory to commercial scale equipment.

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

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 powderswas 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 6μg/ml for both powders compared to 0.02 ± 0.01μg/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.

Characterization of Inclusion Complex of Croton zehntneri Essential Oil and β-Cyclodextrin Prepared by Spray Drying and Freeze Drying

Croton zehntneri (CZ) is an aromatic species of the Euphorbiaceae family, native to Northeast of Brazil, rich in essential oil (CZEO) with antioxidant, vasorelaxant, bactericidal and fungicidal properties. Despite the numerous biological and pharmacological potentials, essential oils are unstable and have limited solubility in water, characteristics that can be improved by the formation of inclusion complexes with cyclodextrins (CDs). In the present study, the inclusion complex of CZEO and β-CD was prepared by co-precipitation coupled to freeze drying and spray drying. The inclusion complex was characterized by vibrational spectroscopy (Raman spectroscopy and FT-IR) and the complexation efficiency determined by gas chromatography coupled to mass spectrometry (GC-MS). It was observed that co-precipitation coupled to lyophilization allowed greater complexation efficiencies when compared to the spray drying. Raman spectroscopy confirms the formation of the inclusion complex of β-CD and CZEO by both preparation methods.

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

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)] (PBSA) 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.

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

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.

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

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.

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

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.

Modern frontiers and applications of spray‐freeze‐drying in design of food and biological supplements

AbstractSpray‐freeze‐drying (SFD) is a unique tandem technique combining spray drying (SD) and freeze drying (FD), and exploiting the advantages of both. SFD is particularly suitable for volatiles, biologicals, and food supplements that are sensitive to process extremities of temperature (SD) and time and cost (FD). Although SFD has been an area of interest to scientists for some time, there have been few very interesting investigations in food science in the recent past, which highlight the versatility and utility of this method, and been discussed in this review. The sources for SFD range from flavor ingredients to vegetables, lipids, enzymes, vitamins, and proteins. The extensive research findings in this domain have been collated in this focused review with the objective of providing the readers an essence of the forays made in this technology and the future possibilities it promises.Practical applicationsSpray‐freeze‐drying is suitable for volatiles, biologicals, and food supplements that are sensitive to process extremities of temperature (spray drying) and time and cost (freeze drying). Applications of SFD range from flavor ingredients to vegetables, lipids, enzymes, vitamins, and proteins. It offers reduced drying time, higher retention of bioactives postdrying, and improved rehydration, which makes it a method of choice. Considering the possibilities that this technique offers, further research on more types of feed is warranted, that would benefit industry and academia both.

Application of disaccharides alone and in combination, for the improvement of stability and particle properties of spray-freeze dried IgG

Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.Methods: Induced soluble aggregates were quantified at 0 and 3 months, and 45 °C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12 µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules.

Using two-fluid nozzle for spray freeze drying to produce porous powder formulation of naked siRNA for inhalation

Spray freeze drying is an attractive technology to produce powder formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF ∼57%). A direct comparison between the hsDNA and siRNA formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.

Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1–5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.

Obtaining functional powder tea from Brazilian ginseng roots: Effects of freeze and spray drying processes on chemical and nutritional quality, morphological and redispersion properties

In this work, the aqueous extract obtained from Brazilian ginseng (Pfaffia glomerata) roots (BGR), rich in beta-ecdysone and fructooligosaccharides (FOS), was powdered by spray drying and freeze drying techniques aiming to obtain a novel functional food product. The effects of these drying techniques on the chemical and nutritional quality, morphological and redispersion properties of the BGR powders were evaluated. The BGR powders obtained by both spray drying and freeze drying techniques maintained their beta-ecdysone and FOS contents after drying, demonstrating the stability of these functional compounds. It was found that the wettability of the powders obtained by different treatments was affected by the drying technique because freeze-dried particles reached the lower values (66 ± 5 s) while spray-dried particles showed a greater time for dispersion into water (150 ± 25 s). This behavior was mainly associated with differences between powder morphological properties since the freeze-dried particles presented a more porous structure, resulting in a greater water diffusivity into microstructure during the redispersion process. Drying process did not affect the storage stability of powders because the glass transition temperature (Tg) for both samples was approximately 160 °C at a relative humidity of 56%. Thus, both BGR powders presented adequate redispersion properties to constitute a new functional tea or even to be used as a functional ingredient in food products.

A nonconventional method for drying of Pseudomonas aeruginosa and its comparison with conventional methods

In this study, preparation of dried cultures of Pseudomonas aeruginosa using nonconventional drying method, namely, low-temperature low-humidity (LTLH) drying was investigated. The effect of carrier materials (whey protein, corn starch, and trehalose) was examined one at a time and also in combinations (to explore the synergistic effect). The results were compared with those obtained using spray drying and freeze drying in terms of cell survival and dry cell powder yield. The powder samples were analyzed also for morphology, flowability, particle size, and moisture content. In LTLH drying, good cell survival was observed along with high powder yield when compared with that in spray drying. Corn starch showed the highest cell survival (91%) and powder yield (94%, w/w) among the carrier materials employed besides resulting in good cell survival (65%) even after a storage period of 6 months.

A REVIEW ON FAST DISSOLVING TABLET

The convenience of administration and improved patient compliance are important in the design of oral drug delivery system which remains the preferred route of drug delivery inspite of various disadvantages. Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. The popularity and usefulness of the formulation resulted in development of several FDT technologies. These techniques render the disintegration of tablet rapidly and dissolve in mouth in five seconds without chewing and the need of water which is advantageous mainly for pediatrics, geriatrics and patients having difficulty in swallowing tablets and capsules. Formulation of a convenient dosage form for administration, by considering swallowing difficulty and poor patient compliance, leads to development of orally disintegrating tablets. Conventional preparation methods are spray drying, freeze drying, direct compression, Molding, and sublimation while new technologies have been developed for the production of orodispersible tablets.&#x0D; Keywords: Fast Dissolving Tablet, drug delivery system, fast disintegrating, fast melting.

Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals.

Solid dosage forms of biopharmaceuticals such as therapeutic proteins could provide enhanced bioavailability, improved storage stability, as well as expanded alternatives to parenteral administration. Although numerous drying methods have been used for preparing dried protein powders, choosing a suitable drying technique remains a challenge. In this review, the most frequent drying methods, such as freeze drying, spray drying, spray freeze drying, and supercritical fluid drying, for improving the stability and bioavailability of therapeutic proteins, are discussed. These technologies can prepare protein formulations for different applications as they produce particles with different sizes and morphologies. Proper drying methods are chosen, and the critical process parameters are optimized based on the proposed route of drug administration and the required pharmacokinetics. In an optimized drying procedure, the screening of formulations according to their protein properties is performed to prepare a stable protein formulation for various delivery systems, including pulmonary, nasal, and sustained-release applications.

Powdered yoghurt produced by spray drying and freeze drying: a review

Abstract Yoghurt is one of the dairy products most consumed worldwide but dehydrated yoghurt is still uncommon. Considered a nutritious food, yoghurt powder could be used as an ingredient or supplement in juices, cookies, ice cream and dairy beverages. Spray drying and freeze drying are the methods most widely used to dehydrate dairy products, and the process conditions are directly associated with the production costs and value of the final product. Due to osmotic and thermal stress during dehydration, it is often necessary to incorporate agents such as carriers, thermal protectants, cryo-protectants and stabilizers in order to improve the process yield, preserve nutrients and even facilitate rehydration of the product. Thus the present review presents the technologies available to obtain yoghurt powder, including the processes, drying agents, drying rates, rehydration conditions and survival of the lactic acid bacteria.

Ultrasonic spray-freeze drying of partially purified microbial transglutaminase

Ultrasonic spray-freeze drying (USFD) was evaluated to produce partially purified microbial transglutaminase (mTGase) powder, and the effects of the process conditions (a nozzle frequency of 48–120kHz and a flow rate of 2–8ml/min) on enzyme activity and particle size were determined. Furthermore, the relative activity changes at each step of USFD and the behavior of the dried enzyme at extreme pH levels, high temperature and presence of the metal ions were investigated. Additionally, the final product produced by USFD and the powder produced by conventional freeze drying (CFD) were compared in terms of relative activities and physical properties. The results showed that atomizing conditions affected the particle size and, hence the enzyme activity. The enzyme activity was enhanced by ultrasonic atomizing at all conditions while most of the activity loss occurred in the drying step. The USFD provided higher enzyme activity, smaller particle size, better particle morphology and better reconstitution properties than CFD, which are explained by the ultrasonic atomizing and accelerated freezing steps of USFD. Also, the USFD sample preserved its stability in tough conditions, such as extreme pH levels, high temperature and the presence of metal ions better than the CFD counterpart.

Influence of process variables on physical characteristics of spray freeze dried cellulose nanocrystals

This study compares the characteristics of cellulose nanocrystal (CNC) agglomerates prepared using spray drying, freeze drying, and spray freeze drying. Moreover, the effect of the concentration of CNC in the initial aqueous dispersion (~ 0.5–10.0 wt%) on the morphology, particle size distribution, porosity and crystalline structure of the spray freeze dried CNC agglomerates were investigated. Scanning electron microscopy was used to characterize the morphology and particle size distribution, nitrogen adsorption–desorption isotherms were used to analyze the porous structure of the particles, and X-ray diffraction was used to analyze the crystalline structure of the particles. Spray drying of CNC resulted in 0.5–30 μm dense agglomerates of slightly deformed elliptical and mushroom cap shaped particles with no porous structure. Freeze drying resulted in large irregular shape flakes of various sizes ranging mainly between 150 and 350 μm. On the other hand, spray freeze drying of CNC from dilute suspensions (~ 0.5 wt%) resulted in larger (4–240 μm) light spherical particles that were highly porous (~ 110 times larger in BET surface area), with web-like inter-connected structure consisting of 10–30 nm thick nanofibrils. Increasing the concentration to 5 wt% produced slightly denser spherical particles (13–110 μm) with slightly less porous web-like structure.