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Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery

Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery

Heiko Schiffter, Jamie Condliffe, Sebastian Vonhoff

Abstract

The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 µm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (<10 mg ml−1) and subsequent ultra-turrax homogenization. To prepare particles for needle-free ballistic injection, the insulin nanoparticles were suspended in matrix formulations with a high excipient content (>300 mg ml−1) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (Tprod) exceeded the glass transition temperature of the freeze concentrate (Tg′) of −29.4°C for TMDD (3∶3∶3∶1) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin loading, the d (v, 0.5) of the SFD powders increased and particle size distributions got wider. Insulin showed a good stability during the particle formation process with a maximum decrease in insulin monomer of only 0.123 per cent after SFD. In accordance with the SEC data, FTIR analysis showed only a small increase in the intermolecular β-sheet of 0.4 per cent after SFD. The good physical stability of the polydisperse particles made them suitable for ballistic injection into tissue-mimicking agar hydrogels, showing a mean penetration depth of 251.3 ± 114.7 µm.

Keywords

spray-freeze-drying, needle-free injection, insulin delivery, nanosuspensions, protein formulation

Happy holidays

In January 20, 2018 PowderPro celebrate 18 years of business with our Freeze Granulation equipment making high quality and homogeneous granules of different powders and materials.

During 2018 our plan is to develop an industrial and commercial version of our PS-20 prototype.

We wish all of our customers a Merry Christmas & A Happy New Year 2018!
This year we have chosen to donate money to UNHCR.

A spray-freezing approach to reduced graphene oxide/MoS2 hybrids for superior energy storage

A spray-freezing approach to reduced graphene oxide/MoS2 hybrids for superior energy storage

Tao Cheng, Jin Xu, Ziqi Tan, Jianglin Ye, Zhuchen Tao, Zhenzhen Du, Ying Wu, Shuilin Wu, Hengxing Ji, Yan Yu. Yanwu Zhu

Abstract

A three-dimensional (3D) architectural hybrid, composed of reduced graphene oxide (RGO) and ultrathin MoS2 layers, is fabricated by a facile spray-freezing method. The spray-freezing to liquid nitrogen rapidly freezes the precursor droplets which avoids phase separation and restacking of MoS2 and RGO platelets, and the following drying/annealing results in the porous 3D structure. The as-prepared 3D architectural RGO/MoS2 hybrid has a high surface area of 128 m2 g−1, a porous structure and a good electrical conductivity. In LIBs, the capacity of RGO/MoS2 anode (with an optimized MoS2 content of 55 wt%) remains 1197 mAh g−1 after 400 cycles of measurement at a current density of 1 A g−1 and it remains 892 mAh g−1 over 400 cycles at a current density of 2 A g−1. A capacity of 723 mAh g−1 is obtained at a current of 10 A g−1. As for the anode (with an optimized MoS2 content of 74 wt%) in SIBs, a high initial discharge capacity of 1315 mAh g−1, a superior rate capacity of 470 mAh g−1 at 1 A g−1 and an excellent cycling stability (518 mAh g−1 after 200 cycles at 0.5 A g−1) are demonstrated.

Keywords

Reduced graphene oxide, Molybdenum disulfide, Lithium ion batteries, Sodium ion  batteries, Electrochemistry

Development of Inhalable Dry Powder Formulations Loaded with Nanoparticles Maintaining Their Original Physical Properties and Functions

Development of Inhalable Dry Powder Formulations Loaded with Nanoparticles Maintaining Their Original Physical Properties and Functions

Okuda T

Abstract

Functional nanoparticles, such as liposomes and polymeric micelles, are attractive drug delivery systems for solubilization, stabilization, sustained release, prolonged tissue retention, and tissue targeting of various encapsulated drugs. For their clinical application in therapy for pulmonary diseases, the development of dry powder inhalation (DPI) formulations is considered practical due to such advantages as: (1) it is noninvasive and can be directly delivered into the lungs; (2) there are few biocomponents in the lungs that interact with nanoparticles; and (3) it shows high storage stability in the solid state against aggregation or precipitation of nanoparticles in water. However, in order to produce effective nanoparticle-loaded dry powders for inhalation, it is essential to pursue an innovative and comprehensive formulation strategy in relation to composition and powderization which can achieve (1) the particle design of dry powders with physical properties suitable for pulmonary delivery through inhalation, and (2) the effective reconstitution of nanoparticles that will maintain their original physical properties and functions after dissolution of the powders. Spray-freeze drying (SFD) is a relatively new powderization technique combining atomization and lyophilization, which can easily produce highly porous dry powders from an aqueous sample solution. Previously, we advanced the optimization of components and process conditions for the production of SFD powders suitable to DPI application. This review describes our recent results in the development of novel DPI formulations effectively loaded with various nanoparticles (electrostatic nanocomplexes for gene therapy, liposomes, and self-assembled lipid nanoparticles), based on SFD.

Keywords

aerosol delivery; dry powder inhaler; powder-particle design; reconstituted nanoparticle; spray-freeze drying

Shrinkage of spray-freeze-dried microparticles of pure protein for ballistic injection by manipulation of freeze-drying cycle

Shrinkage of spray-freeze-dried microparticles of pure protein for ballistic injection by manipulation of freeze-drying cycle

Straller G, Lee G

Abstract

Spray-freeze-drying was used to produce shrivelled, partially-collapsed microparticles of pure proteins that may be suitable for use in a ballistic injector. Various modifications of the freeze drying cycle were examined for their effects on collapse of the pure protein microparticles. The use of annealing at a shelf temperature of up to +10°C resulted in no visible particle shrinkage. This was because of the high Tg’ of the pure protein. Inclusion of trehalose or sucrose led to particle shrinkage because of the plasticizing effects of the disaccharides on the protein. Only by extending the duration of primary drying from 240 to 2745min at shelf temperatures in the range -12 to -8°C were shrivelled, wrinkled particles of bSA and bCA of reduced porosity obtained. Manipulation of the freeze-drying cycle used for SFD can therefore be used to modify particle morphology and increase particle density.

Keywords

Ballistic injector; Collapse; Protein; Spray-freeze-drying

Mechanical particle coating using polymethacrylate nanoparticle agglomerates for the preparation of controlled release fine particles: The relationship between coating performance and the characteristics of various polymethacrylates.

Mechanical particle coating using polymethacrylate nanoparticle agglomerates for the preparation of controlled release fine particles: The relationship between coating performance and the characteristics of various polymethacrylates.

Kondo K, Kato S, Niwa T

Abstract

We aimed to understand the factors controlling mechanical particle coating using polymethacrylate. The relationship between coating performance and the characteristics of polymethacrylate powders was investigated. First, theophylline crystals were treated using a mechanical powder processor to obtain theophylline spheres (<100μm). Second, five polymethacrylate latexes were powdered by spray freeze drying to produce colloidal agglomerates. Finally, mechanical particle coating was performed by mixing theophylline spheres and polymethacrylate agglomerates using the processor. The agglomerates were broken under mechanical stress to coat the spheres effectively. The coating performance of polymethacrylate agglomerates tended to increase as their pulverization progressed. Differences in the grindability of the agglomerates were attributed to differences in particle structure, resulting from consolidation between colloidal particles. High-grindability agglomerates exhibited higher pulverization as their glass transition temperature (Tg) increased and the further pulverization promoted coating. We therefore conclude that the minimization of polymethacrylate powder by pulverization is an important factor in mechanical particle coating using polymethacrylate with low deformability. Meanwhile, when product temperature during coating approaches Tg of polymer, polymethacrylate was soften to show high coating performance by plastic deformation. The effective coating by this mechanism may be accomplished by adjusting the temperature in the processor to the Tg.

Keywords

Dry fine particle coating; Glass transition temperature; Grindability; Mechanical powder processing; Polymethacrylate; Spray freeze drying

Preparation and Characterization of Pentoxyverine Citrate Micro-Nano Particle Aggregations

Preparation and Characterization of Pentoxyverine Citrate Micro-Nano Particle Aggregations

Bo Chen, Hui Tang, Yong Peng Huang, Jian Lan Jiao, Chuan Pin Zou

Abstract

Micro-nano drug particle aggregations were prepared by shearing emulsification, high pressure homogenization and spray freeze drying, particle formational process and optimization of preparation conditions were analyzed, and micro-morphologies, particle size distributions, aerodynamic properties, release performances, inhalation and deposition properties were characterized. Results show that the optimum condition is drug supersaturation 2 and liquid feeding rate 800 mL/h. Micro morphologies of aggregations are porous spherical foamy structure formed by flaky micro-nano particles. The aggregations obtain both of the advantages of low density and large porous particles and micro-nano superficial particles. Tap density is only 0.062 g mL-1, mass median aerodynamic diameter is 0.93μm, aerosol availability is 59.8%, fine particle fraction is 15.80%, and more than 99% drugs dissolve within 5 min. All above properties are effective for drug delivery and release of DPI.

Keywords

Characterization, Dry Powder Inhalation, Micro-Nano Particle Aggregation, Pentoxyverine Citrate, Spray Freeze Drying

Structured emulsion-templated porous copolymer based on photopolymerization for carbon capture

Structured emulsion-templated porous copolymer based on photopolymerization for carbon capture

Dariush Nikjoo, Farid Akhtar

Abstract

Porous hydrogel copolymers of acrylamide (AAM) and acrylic acid (AAC) were structured in the form of monoliths and granules. AAM-co-AAC porous copolymer monoliths were synthesized using high internal phase emulsion (HIPE) as template and photopolymerization. For granulation, photopolymerization was used for the fabrication of the AAM-co-AAC hydrogel, which was subsequently freeze-granulated. The structural analysis (FTIR and XRD) confirmed the successful synthesis of hydrogel copolymers. The CO2 uptake capacity of structured AAM-co-AAC copolymers was evaluated through adsorption and absorption mechanisms by volumetric and gravimetric methods, respectively. The granules exhibited the CO2 adsorption uptake of 0.8 mmol g−1 at 25 kPa and 298 K. The CO2 and N2 adsorption data demonstrated that the hydrogel copolymers were selective for CO2. Furthermore, the granules were capable of capturing CO2 in the presence of water. The results of absorption of CO2 on water-swollen granules demonstrated that CO2-uptake capacity increases with increasing water content up to 1.8 mmol g−1.

Keywords

Porous polymer, Photopolymerization, Adsorption, Absorption, Carbon capture

Phase change and droplet dynamics for a free falling water droplet

Phase change and droplet dynamics for a free falling water droplet

K.R. Sultana, K. Pope, L.S. Lam, Y.S. Muzychka

Abstract

This paper numerically examines phase change of free falling droplets in a sub-zero environment. The model is based on the solution of the Navier-Stokes equations coupled with the Volume of Fluid (VOF) methodology for tracking the droplet-air interface. A 2D axisymmetric model is adopted to implement the influential numerical parameters. The phase change phenomenon of fresh and salt water droplets with constant and variable properties are considered in this model. Current results reveal that the internal circulation enhances heat transfer to the surrounding air and increases the nucleation phenomenon. Furthermore, larger sized droplets have a higher nucleation temperature than the smaller sized droplets. The computational results are compared to previously published experimental data for nucleation and droplet dynamics. The results of this paper provide new insights on phase change and droplet dynamics and contribute to the understanding of mechanisms involved with spray freezing applications.

Keywords

Computational fluid dynamics, Droplet, Nucleation, Sub-zero environment, Thermophysical properties

Improving quercetin dissolution and bioaccessibility with reduced crystallite sizes through media milling technique

Improving quercetin dissolution and bioaccessibility with reduced crystallite sizes through media milling technique

Muwen Lu, Chi-Tang Ho, Qingrong Huang

Abstract

Quercetin (QC) is a common bioflavonoid with low water solubility, which limits its oral bioavailability and in vivo beneficial functions. To enhance QC bioaccessibility, QC nanoparticles were produced using the media milling technology. Hydrophobically modified starch (HMS) was added with the ratio of 1:1 to QC as a stabilizer to prevent the agglomeration of QC particles. The QC nanodispersions were either spray-dried or freeze-dried after media milling process. Physicochemical characteristics of dried QC powders were measured through dynamic light scattering (DLS), Fourier Transform-Infrared spectroscopy (FTIR), dissolution test and X-ray diffraction (XRD). The detailed crystallite structures were carefully analyzed. The TNO dynamic gastro-intestinal model-1 (TIM-1) was utilized to study the in vitro QC bioaccessibility by simulation of the digestive processes in the upper GI tract. This study suggests that media milling technique combined with spray/freeze-drying treatment is an efficient processing method for the development of crystalline nutraceuticals-based functional food products with reduced crystallite sizes and enhanced metastable equilibrium solubility, dissolution and bioaccessibility.

Keywords

Quercetin, Nanoparticle, Wet milling, Dissolution, Bioaccessibility