Investigation of fluidization regimes and coating process for alginate aerogel particles in a wurster fluidized bed

Aerogels are solid materials with high porosities, open and inter-connected pore structures, and high surface areas. Over the last decade, there are an increasing number of research efforts concerning in coatings of aerogels since the combination of the porous structure of aerogels with the morphological, mechanical, and functional properties of a coating material leads to outstanding performances in different applications. In this study, coating process was investigated for highly porous alginate aerogel particles in a laboratory scale Wurster fluidized bed. In the first part of this study, fluidization regimes for alginate aerogel particles with two different particle sizes were characterized in the Wurster fluidized bed both in the annular zone and the tube zone without spraying. For both particle sizes, minimum fluidization and bubbling regimes were observed both in the zones whereas pneumatic regimes existed only in the tube zone. Moreover, a new regime which was horizontal circular motion was identified for large particles in the tube zone. There existed two other regimes in the bed which were turbulent and circulatory particle motion regimes. All fluidization regimes were mapped on Kunii and Levenspiel diagrams. Circulatory particle motion regime was given on these diagrams for the first time. Furthermore, effects of particle size, batch volume, Wurster tube size, perforated plate geometry and partition gap height on the boundaries of each fluidization regime were investigated by measuring superficial air velocities at the onset and the end of each regime. In general, increasing particle size and partition gap height led to an increase in superficial air velocities at the onset and the end of each regime. With increasing tube diameter and tube length, superficial air velocities at the onset and the end of pneumatic, turbulent and circulatory particle motion regimes increased. Increasing batch volume for small particles caused a decrease in superficial air velocities at the end of bubbling and pneumatic regimes and the onset of turbulent and pneumatic regimes. At the onset and the end of bubbling, turbulent and pneumatic regimes, superficial air velocities for large particles for 400 ml batch volume were higher than superficial air velocities for large particles for 200 ml batch volume. In this part, circulatory particle motion regime which is desirable for a successful coating process was particularly investigated in detailed. The results showed that there is an upper limit for each parameter to obtain a circulatory motion of the particles. It was found that the partition gap height should be 2 cm for proper particle circulation. Maximum batch volume for the tube with 10 cm diameter was found as 500 ml whereas maximum batch volume was 250 ml for the tube with 8 cm diameter. In the second part of this study, alginate aerogel particles were successfully coated with an aqueous polymer solution in a Wurster fluidized bed without damaging the pores of aerogels. The polymer was a mixture of hydroxypropyl cellulose (HPC) and copovidone and is generally used as a protective coating for pharmaceutical dosage forms. Variations occurring in coating layer thickness around alginate aerogel particles and changing coating layer surface morphology with coating time, bed temperature, atomizing air pressure and polymer rheology were investigated for the first time. Moreover, phase and rheological behavior of the coating polymer solution and individual solutions of HPC and copovidone were studied at different temperatures to understand their spreading and adhesion mechanisms on aerogel surfaces. Several sets of experiments were conducted at three different bed temperatures and atomizing air pressures. Coating time for all the runs ranged from 5 minutes to 40 minutes and the coating layer thickness ranged from 12.4 ± 4.6 µm to 170.6 ± 43.3 µm. The smoothest coating layer surface and the highest coating efficiency which was 69.2 ± 0.4 % with a linear increase in coating layer thickness were achieved at 50 °C with 1.7 bar. An increase in atomizing air pressure from 1.5 bar to 1.7 bar resulted in a smoother coating layer. A high mean coating polymer solution droplet velocity with a narrow droplet size distribution led to a homogeneous spreading and less variance in coating layer thickness at 1.7 bar. It was found that changing bed temperature led to more important changes in coating layer thickness compared to atomizing air pressure whereas both bed temperature and atomizing air pressure affected coating layer surface morphology to a great extent. Finally, drug loaded, and unloaded alginate aerogel particles were successfully coated with a methacrylic acid-ethyl acrylate copolymer aqueous solution using a Wurster fluidized bed. For unloaded aerogels, atomizing air pressure was set to 1.7 bar depending on optimized conditions obtained in the protective coating. To prevent particle breakage and provide an increase in coating layer thickness, atomizing air pressure was changed during the coating process for drug loaded aerogels between 1.3 bar and 1.5 bar. The highest coating layer thickness was 50 ± 5 μm and was reached in 50 minutes for unloaded aerogels whereas coating layer thickness was found as 83.8 ± 11.9 μm in 3 hours for drug loaded aerogels. Two different coating layer surface morphologies on the coating layer were observed as bead and fiber for both unloaded and loaded aerogels. Rheology experiments showed that coating polymer stayed stable in a wide range of frequency domain and its viscosity was nearly constant in lower Newtonian region in applied atomizing air pressure range. Therefore, different coating mechanisms at different atomizing air pressures may lead to bead and fiber shaped surface morphologies. Subsequently, drug loaded, and coated alginate aerogels were used as drug carriers. Ibuprofen was used as a model drug and its release from coated and uncoated aerogels were investigated both in the acidic and basic mediums. It was first time shown in the literature, ibuprofen release in the acidic medium was prevented via synergetic effects of coating polymer with a proper coating layer thickness and alginic acid layer around the aerogels. In the basic medium, uncoated and coated aerogels provided different release profiles compared to the release profile of crystalline ibuprofen. Enteric coating led to a decrease in the release rate whereas ibuprofen release rate was increased with uncoated aerogels.