Solid dispersion particles were prepared using an indomethacin (IND) as a model insoluble drug, poly-(vinylpyrrolidone-co-vinyl acetate) (VA64) as a water-soluble polymer and mannitol (Man) as an excipient. In case of hot-melt extrusion (HME) preparation, dissolution profile of every composition without Man was the same as others. The dissolution profile of composition including Man was much improved than others without Man. By contrast, the effect of Man addition was not recognized in case of spray drying (SD) preparation. Surface energy of the solid dispersion particles was measured by using an inverse gas chromatography surface analyzer (iGC-SEA). The surface energy of solid dispersion particles including Man prepared by the HME is much smaller than that without Man. However, in the SD preparation, there was no clear difference in the surface energy of solid dispersion particles with and without Man. The characteristic of the solid dispersion particles by the different manufacturing methods implied the difference of the dissolution improvement, in spite of the same composition.
This review gives a brief description of major computational methods to simulate the dynamics of particles at liquid–liquid or liquid–vapor interfaces. The particle-resolved simulation models based on the direct numerical simulation of Navier–Stokes equation and the lattice Boltzmann method (LBM) are surveyed. In addition, we explain a numerical model based on the smoothed-profile LBM for the treatment of moving solid particles in a fluid and the free-energy LBM for the description of a liquid-vapor system. Typical simulation results presented here indicate that the particle-resolved simulations can be an effective approach to explore the particle–fluid–fluid systems.
Content uniformity of Active Pharmaceutical Ingredients (APIs) is one of the most important quality issue in drug products and it can be a particularly serious in case of low content formulations. CTS-SGR (Continuous Spray Granulator) is a continuous granulator that produces granules directly from raw materials dissolved or dispersed in a liquid, so that the product granules will have a uniform composition if the ingredients in the spray solution is uniformly dissolved or dispersed. Here, we report the application of CTS-SGR to the production of granules containing low API content. Especially, mini-tablets could be successfully produced from the granules with less variation in content.
Continuous crystallization is the next step of manufacturing especially at the production of pharmaceutical ingredients. We have developed small-scale continuous taylor-vortex crystallizer that is suitable for research in laboratory. But there was a problem that rotating inner cylinder at high-speed range causes much frictional heat and it raises the temperature of the solution, that may spoil the effort of controlling characteristics of crystals. So, we have developed new taylor-vortex crystallizer that has inner cooling system. We conducted several examinations of anti-solvent crystallization of glycine, which aims to obtain unstable crystal polymorph of glycine continuously. The new crystallizer showed the advantage of crystallizing unstable crystal polymorph.