Suhas D. Shelukar

Identification and characterization of factors controlling tablet coating uniformity in a Wurster coating process

Abstract The product coating uniformity in the Wurster column coating process is primarily determined by two factors — the coating-per-pass distribution and the circulation-time distribution. Experimental techniques were developed for a tablet-coating system to quantify these two factors. A magnetic-tracing technique was used to measure the circulation time, circulation-time distribution, and the number of passes made by the tablets during the coating process. The coating-per-pass and total-coating distributions were measured by a dye tracing technique. The circulation time decreased and the circulation-time distribution became narrower as the inlet air flow rate and the partition gap increased. A tail on the circulation-time distribution at low air flow rates and low partition gaps indicated the formation of dead/slow zones, which could result in non-uniform coating. Modifications to the distributor plate resulted in a narrow circulation-time distribution. The coating-per-pass distribution contributed significantly (>75%) to the total-coating uniformity. This was due to the broad coating-per-pass distribution, measured by coating the tablets for one pass only. The contribution due to the coating per pass increased with increase in the partition gap. The broad coating-per-pass distribution was due to differences in the proximity of the tablets to the spray zone, pulsing flow of the tablets, and tablet-to-tablet sheltering. High-speed video imaging in the spray zone confirmed the cause of the broad coating-per-pass distribution. Optimal total-coating uniformity requires process conditions that give narrow coating-per-pass and circulation-time distributions. Thus, the quantitative techniques developed serve as powerful tools to characterize and optimize the coating process.

Characterization of Crystalline Drug Nanoparticles Using Atomic Force Microscopy and Complementary Techniques

AbstractPurpose. The purpose of this work was to image crystalline drug nanoparticles from a liquid dispersion and in a solid dosage form for the determination of size, shape, and distribution. Methods. Crystalline drug nanoparticles were adsorbed from a colloidal dispersion on glass for atomic force microscopy (AFM) imaging. Nanoparticles that were spray coated onto a host bead were exposed by ultramicrotomy for scanning electron microscopy and AFM examination. Results. The adsorbed drug nanoparticles were measured by AFM to have a mean diameter of 95 nm and an average aspect ratio of 1.3. Nanoparticles observed in the solid dosage form had a size and shape similar to drug nanoparticles in the dispersion. Particle size distribution from AFM measurement agreed well with data from field emission scanning electron microscopy, static light scattering, and X-ray powder diffraction. Conclusions. AFM is demonstrated to be a valuable tool in visualization and quantification of drug nanoparticle crystals in formulations. In addition to accurate size measurement, AFM readily provides shape and structural information of nanoparticles, which cannot be obtained by light scattering. Ultramicrotomy is a good sample preparation method to expose the interior of solid dosage forms with minimal structural alteration for microscopic examination.