Browsing by Subject "spray drying"

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  • Kainulainen, Saila (Helsingin yliopisto, 2020)
    The solubility of a poorly water-soluble drug can be improved by converting the crystalline drug into an amorphous form. However, the amorphous form is metastable due to the higher energy state and recrystallization may occur during storage and dissolution. The amorphous form can be stabilized by forming an amorphous solid dispersion (ASD), where the drug molecules are dispersed to the solid medium, e.g. hydrophilic polymer. One preparation method for amorphous solid dispersions is spray drying, where a solution containing a drug and polymer is converted into small droplets in a drying chamber, in which the solvent evaporates in a hot gas stream and solid particles are formed. The aim of this study was to investigate whether an ASD of a poorly water-soluble drug can be prepared by spray drying using 20:80 (V/V) ethanol-water mixture as a solvent in a feed solution. Indomethacin (γ-polymorph) was used as a model drug and polyvinylpyrrolidone vinyl acetate (PVPVA) as a polymer. The aim was to find a suitable formulation where the drug is in the amorphous form after spray drying and remains in the amorphous form during storage. The ratios of the drug to polymer in the spray-dried formulations were 1:4, 1:6, 1:8, 1:10, 1:12 and 1:16. The study also examined whether a change in one process parameter, pump feed rate, affects the amorphous nature and stability of the resulting spray-dried solid dispersions. Two different pump feed rates, a higher 30% and a lower 15%, were used in the study. X-ray powder diffraction (XRPD) was used to characterize the solid-state of the spray-dried formulations. XRPD measurements were performed immediately after spray drying and on selected time points during storage. Formulations 1:10 at 30% feed rate, 1:12 at both feed rates and 1:16 at 30% feed rate were amorphous after spray drying. In 1:12 (30%) and 1:16 (30%) formulations indomethacin remained in amorphous form over the study periods (22 and 56 days, respectively). In other formulations, indomethacin was found to be in crystalline α-form immediately after spray drying or recrystallization to the α-form occurred during storage. The interaction between indomethacin and PVPVA was studied by surface plasmon resonance spectroscopy (SPR). The aim of the SPR measurements was to understand the interaction between these substances in the feed solution used in spray drying. PVPVA solutions of various concentrations (1%, 0.5%, 0.1% and 0.01%) were injected to the surface of the gold sensor coated with crystalline γ-indomethacin, and the changes in the SPR signal responses were monitored during the interaction. The same measurements were also performed on a pure gold sensor without indomethacin. An interaction between indomethacin and PVPVA can be observed, and based on the measurements, a polymer layer with a thickness of about 1 nm was formed on the surface of the indomethacin sensor regardless of the concentration of the polymer solution. Thus, even a small amount of polymer in solution is sufficient to cover the indomethacin crystals. This may also occur in the feed solution during spray drying, but further studies with SPR are still needed, especially with amorphous indomethacin. This study showed that an ASD of indomethacin and PVPVA can be successfully prepared by spray drying using an aqueous feed solution. Spray-dried 1:12 and 1:16 formulations at a higher pump feed rate were found to be stable enough for further studies. If the spray-dried material is further formulated into a pharmaceutical product, indomethacin must remain in amorphous form throughout the shelf-life of the product to maintain the improved solubility.
  • Kolu, Anna-Maija (Helsingfors universitet, 2013)
    Spray drying is one way to dry protein medicines and it has many advantages compared to other drying methods, for example it is a fast process. In spray drying high temperature and mechanical stress can inactivate the protein. Disaccharides are generally used as protective agents of protein in spray drying because they have an ability to protect the structure of the protein during drying and storage. Aim of this research was to study the stability of the protein during spray drying and storage by using β-galactosidace as a model protein. Aim was also to characterize the physical properties of trehalose and melibiose and to study how well they protect the protein. Some of the central matters to be examined were the glass transition temperature, crystallinity, water activity, yield of the spray dried powder and protein activity. Especially studying the properties of melibiose in spray drying was important because it has not been used before. The study also included the optimization of the process parameters to be suitable for the product. Trehalose and melibiose transformed to an amorphous form during spray drying. Both XRPD and DSC showed an amorfous form. Trehalose and melibiose proved to be good protective agents for the protein during spray drying and storatge probably because they remained their amorphous structure. β-galactosidase remained activity very well. Optimizing of the process parameters was successful because protein remained its activity and still the powder was quite dry and yield was good. The changes in the structure of the protein were studied with FT-IR but the amount of the protein was too small. Problems caused by the spray drier may have an effect to the results, but on the other hand the spray dryer was made to work optimally.
  • Mikkonen, Tiia (Helsingfors universitet, 2012)
    The literature review dealed with composition of lingonberry, effects of processing on phenolic compounds and spray drying juices with the help of carrier agents. The aim of the experimental work was to spray dry lingonberry juice with the help of carrier agents, examine the properties of juice powders and explore how juice powders suit for selected applications. The total content of phenolic compounds was also measured from the lingonberry juice and powders. Maltodextrin DE 5–8 (MD), whey protein isolate (WPI) and combination of carrier agents (MD+WPI) were used as carrier agents while yield, glass transition temperature, colour, solubility and total content of phenolic compounds were the properties examined. A milk based lingonberry smoothie, lingonberry marmalade, lingonberry marshmallow and lingonberry spread were developed as applications. The spray drying of the lingonberry juice and subsequent applications were successful. The highest yield (20.9%) was achieved when MD was used as a carrier agent. WPI had the lowest yield (9.8%). MD-juice powders had the highest glass transition temperature at all relative humidities used (0, 11, 24, 33 and 44%) and WPI-juice powder had the lowest. Commercial juice powder had the darkest colour (garnet) and MD+WPI-juice powder was the lightest (light pink). MD-juice powder had the poorest solubility and commercial powder had the best, although MD was a carrier agent in both. The total content of phenolic compounds in lingonberry juice was 246.4 mg/100 g and in the best juice powder (WPI) 3.6 mg/100 g. Juice powders had differences in colour when used in applications and smoothies also had differences in stability of foam. MD and commercial powder formed a stabile foam structure but WPI-smoothies separated into liquid and foam phases. Lingonberry juice powders did not affect the structure of marmalades or marshmallows. In lingonberry spreads commercial juice powder blended the best into margarine. Lingonberry juice powders are interesting products. Lingonberry juice powders would suit well in different applications to add colour and taste. Due to low glass transition temperature, powders were difficult to handle. With some further research this stickiness problem could be solved.
  • Pietiläinen, Johannes (Helsingfors universitet, 2013)
    The aim of this study was to obtain basic knowledge of the applicability of a Büchi Spray dryer B-290 for inhalation particle production and its process parameters effects on particle physicochemical properties. The possibility to anneal the particles where also studied. The greater goal was to provide some information about the solutes' crystallization tendency related to chosen process parameters. Two active pharmaceutical ingredients, salbutamol sulphate and budesonide, where chosen as model substances. Spray drying is a suspended particle processing system which is widely applied and it has been in use from the 1940s. The processed pumpable liquid which contains chosen substances is dispersed into droplets and dried to produce particles that are later collected. Spray dryer is used to process food, biochemical and pharmaceutical substances. In the field of inhalation particle processing, however, it is rather a new technology. This is because of the quality limitations of inhalable particles and the challenges in process optimization. From the many process parameters the concentration of the solid substances, inlet temperature and concentration of organic solvent were chosen as variables for the conducted experiments due to their apparent effects on product quality and especially on solid state. A rudimentary box-annealing system was studied for spray dried substances to verify their solid state transformation tendencies. Salbutamol sulphate was annealed in a box with 65% relative humidity and budesonide in 74 % and 100% relative ethanol activities. Particle size and size distributions were measured with laser diffraction apparatus, crystallinity was analyzed with powder x-ray diffraction and particle morphology was studied with scanning electron microscope. Salbutamol sulphate turned out to be amorphous and budesonide crystalline when spray dried. Both products were within the inhalable size range (1-5µm). Under the current setup the solid state quality of the products was found dependent on the concentration of the solid substances to some extent. Spray dried amorphous salbutamol sulphate was successfully anneaed to a crystalline material and partly crystalline budesonide was annealed to a more crystalline state. Further studies are needed to utilize the full potential spray drying has to offer for inhalation formulating. The kinetics of the annealing procedure and its dependency on the method used still remain largely unexplored.
  • Suihkonen, Terhi (Helsingfors universitet, 2013)
    The literature review dealed with the composition of lingonberry, manufacture of juice powder and the effects of different carriers on properties of juice powder, especially glass transition temperature and stickiness. In addition, physical, functional and nutritional properties and the effect of storage conditions on juice powders were covered. The aim of the experimental work was to investigate the effect of spray- and freeze-drying and carriers on glass transition temperature and water sorption of lingonberry juice as well as the stability of vitamin C and phenolic compounds during drying and storage. The same amounts of maltodextrin (MD), whey protein isolate (WPI) or combination of MD/WPI in equal proportions were added to each sample. All samples were spray- and freeze-dried. After storage of powders at different relative humidities, glass transition temperature, water sorption, content of L-ascorbic acid and content of phenolic compounds were examined. Water sorption was examined by static and dynamic vapour sorption methods. The small particle size of containing WPI was problematic with spray-drying because not all of the powder in the drying air could be separated in the cyclone. Adding water back into the spray-dried samples was most difficult when the samples were stored at low relative humidities (0–11%). The smallest water sorption was observed with both static and dynamic vapour sorption methods in samples which contained only MD. Water contents of freeze-dried samples were lower than those of spray-dried samples. BET sorption isotherm described the water sorption behaviour of the lingonberry juice powders well. Glass transition temperatures of all samples decreased as the relative humidity increased. During storage, the amount of phenolic compounds in samples containing WPI remained the same, whereas the amount of phenolic compounds in samples with MD decreased. Enzymatic spectrophotometric determination was un suitable for determing L-ascorbic acid in lingonberry powder because the sample colour disturbed the measurement. MD and the combination of MD and WPI were suitable carriers in lingonberry juice. The amount of phenolic compounds in lingonberry juice powders were preserved well by whey protein isolate. Therefore, the spray-drying process should be developed in a way that brings about increase in particle size of powder containing WPI.