17 research outputs found
Particle generation with liquid carbon dioxide emulsions
Spray drying is a common technique for particle generation. However, due to limitations in the droplet size, the production of solid submicron particles using conventional atomizers has proven to be challenging. With the aim of overcoming this limitation, the generation and expansion of emulsions of an aqueous solution and liquid carbon dioxide with a subsequent drying step was investigated. Potassium chloride concentrations in the solution between 0.1 and 10 wt. % and mass loads of the aqueous disperse phase between 0.01 and 0.09 were used in order to study their impact on the droplet and particle size. For the lowest potassium chloride concentration, median particle diameters in the submicron size range were measured for all mass loads of the disperse phase
Insights into the mechanism of enhanced dissolution in solid crystalline formulations
Solid dispersions are a promising approach to enhance the dissolution of poorly water-soluble drugs. Solid crystalline formulations show a fast drug dissolution and a high thermodynamic stability. To understand the mechanisms leading to the faster dissolution of solid crystalline formulations, physical mixtures of the poorly soluble drugs celecoxib, naproxen and phenytoin were investigated in the flow through cell (apparatus 4). The effect of drug load, hydrodynamics in the flow through cell and particle size reduction in co-milled physical mixtures were studied. A carrier-and drug-enabled dissolution could be distinguished. Below a certain drug load, the limit of drug load, carrier-enabled dissolution occurred, and above this value, the drug defined the dissolution rate. For a carrier-enabled behavior, the dissolution kinetics can be divided into a first fast phase, a second slow phase and a transition phase in between. This study contributes to the understanding of the dissolution mechanism in solid crystalline formulations and is thereby valuable for the process and formulation development
Spray Conditioning for the Preparation of Spray Dried Submicron Particles
[EN] Particle size reduction down to the submicron range (0.1-1 µm) is an effective option to increase the bioavailability
of low water soluble active pharmaceutical ingredients. According to the Nernst-Brunner equation, the preparation
of submicron sized particles increases the specific surface area, thus increases the dissolution rate. Conventional
spray drying devices for submicron particles show certain limitations. The main challenge is the preparation of
small and uniform droplets during the atomisation step. In this work, fine droplets were generated combining a
nozzle with a droplet separator. Therefore, the aerosol is generated with a pneumatic nozzle and is sprayed into a
cyclone droplet separator. Depending on the characteristics of the cyclone, droplets larger than the cut-off-size
were separated and returned into the liquid feed. The conditioned aerosol at the top of the cyclone separator can
then be introduced into the drying chamber. With this concept the usable part is separated, thus no classification
process after drying is necessary. The investigations show that the dependencies during atomisation of the
droplets size on the liquid-to-gas mass flow ratio µm and the liquid properties (e.g. viscosity) do not apply to the
separation step. The conditioned aerosol only depends on the separation characteristics of the cyclone droplet
separator. However, the amount of droplets separated is determined by the atomisation step. Hence, the amount
of droplets smaller than the cut-off-size can be increased by decreasing the droplet size of the primary aerosol.
This is realised by secondary droplet fragmentation. An impact surface causes breakup of the droplets of the
primary aerosol before separation. The investigations show an increased amount of droplets <2µm.Gorny, R.; Schaldach, G.; Walzel, P.; Thommes, M. (2017). Spray Conditioning for the Preparation of Spray Dried Submicron Particles. En Ilass Europe. 28th european conference on Liquid Atomization and Spray Systems. Editorial Universitat Politècnica de València. 162-166. https://doi.org/10.4995/ILASS2017.2017.4701OCS16216
Categorization of sprays by image analysis with convolutional neuronal networks
Spray characterization has been an issue for process and product characterization for decades. Because of this, a convolutional neuronal network was developed to determine the droplet size from spray images. The images were taken using a digital camera, a light source, and a dark room. These were subsequently employed to design and train a convolutional neuronal network using open-source software packages and a desktop computer. The accuracy of the network droplet size determinations was checked with additional, independent images. The median drop size was assessed with a high accuracy of more than 99.8 % as the mean spray performance indicator. Additionally, the droplet size distribution measurements from the neural network method deviated from those from the reference method (laser diffraction) by less than 1.5 %. Convolutional neuronal networks can be applied to determine the spray performance using spray cone images. This approach could be useful for multiple applications
Preparation of micron and submicron particles via spray drying and electrostatic precipitation
Small particles are of great interest in a variety of applications. Spray drying is a common technique for particle synthesis, but it is limited with respect to sizes below 10 μm. Therefore, a new laboratory-scale spray dryer was designed to address this issue. A novel aerosol generator consisting of a piezo crystal in a swirl chamber was designed to obtain droplets in the low micrometer range. After drying and cooling, particles were deposited in a molten carrier, using melt electrostatic precipitation. The median particle size of three pharmaceutical drug substances was 2 μm. The size distribution was particularly narrow, with span values of about 1.1. Spray drying is a sufficient technique to produce small drug particles below 5 μm with ultrasonic atomization at high frequencies. Electrostatic precipitation in a molten carrier is a suitable method to capture these particles
Design and characterization of a melt electrostatic precipitator for advanced drug formulations
Electrostatic precipitators (ESP) are especially known for the efficient separation of micron and submicron particles from aerosols. Wet electrostatic precipitators are particularly suitable for highly resistive materials. Using these, particles can be directly transferred into a liquid for further processing or safer handling, which is advantageous for either hazardous or valuable materials. In this work, a wet ESP, which enables the separation of highly resistive particles into a heated liquid, was designed and investigated. To do this, spray-dried drug particles were embedded in a molten sugar alcohol to enhance the drug dissolution rate. After cooling, the solidified product showed advantageous properties such as a high drug dissolution rate and easy handling for further processing. For the design of the wet ESP, different discharge electrode configurations were tested. A wall film served as the collection electrode, which was generated by a specially designed distributer die. A laminar flow regime was achieved with a homogeneous film serving as the collection electrode, which is particularly important for a high separation efficiency. A prototype was designed and constructed in this respect. The particle separation into hot liquids or onto hot surfaces is challenging due to thermal effects in ESPs. The influence of thermophoresis and drag force on the particle transport was investigated, and optimum operation parameters were found for the present ESP. A broad field of applications can be covered with the presented device, where particles are embedded in even hot liquids to form liquid suspensions or, as it is presented here, solid dispersions. The dissolution of the drug-containing solid dispersion was studied in vitro. A remarkably faster drug dissolution was observed from the solid dispersion, as compared to a powder mixture of the drug and xylitol
Determination of inherent dissolution performance of drug substances
The dissolution behavior of novel active pharmaceutical ingredients (API) is a crucial parameter in drug formulation since it frequently affects the drug release. Generally, a distinction is made between surface-reaction- and diffusion-controlled drug release. Therefore, dissolution studies such as the intrinsic dissolution test defined in the pharmacopeia have been performed for many years. In order to overcome the disadvantages of the common intrinsic dissolution test, a new experimental setup was developed within this study. Specifically, a flow channel was designed and tested for measuring the mass transfer from a flat, solid surface dissolving into a fluid flowing over the surface with well-defined flow conditions. A mathematical model was developed that distinguishes between surface-reaction- and diffusion-limited drug release based on experimental data. Three different drugs—benzocaine, theophylline and griseofulvin—were used to investigate the mass flux during dissolution due to surface reaction, diffusion and convection kinetics. This new technique shows potential to be a valuable tool for the identification of formulation strategies