Browsing by Subject "spray drying"

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.

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.