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Drying is a common pharmaceutical process, whose potential to alter the final drug propertieseven at relatively low temperaturesis often neglected. The present study addresses the impact of drying at 20 and 50 °C on wet-extruded calcium stearate (CaSt) pellets. Drying at 20 °C caused the majority of ibuprofen to accumulate at the pellet surface due to a strong convective flow from the pellet’s center to the surface. In contrast, pellets dried at 50 °C still contained ibuprofen in the pellet’s interior due to the higher drying rate and the associated film breakage during drying. Moreover, the higher drying temperature caused CaSt to form a second lamellar phase and ibuprofen to convert (partly) into its amorphous state. Overall, the drying process affected the solid state and the spatial ibuprofen distribution within the pellet. Knowledge of these effects can aid in tailoring advanced multipellet formulations.

In this paper, a model was developed to describe the catalyst redistribution that occurs during drying of a coimpregnation catalyst. The model takes into account convective flow, catalyst and coimpregnant diffusion, adsorption on the support, and transport in the gas phase. For low catalyst adsorption capacity and low initial coimpregnant concentrations, the system behaves in a manner similar to systems without a coimpregnant. At higher coimpregnant concentration when the coimpregnant has the higher adsorption constant, the catalyst faces strong competition for adsorption sites at the external surface. It therefore migrates toward the center where free sites are available. If the catalyst has the higher adsorption constant, it adsorbs preferentially at the surface, and the coimpregnant hinders the back-diffusion of the catalyst. This can lead to rather sharp egg-shell profiles. Finally, we discuss how to develop a drying strategy that will lead to a desired catalyst profile.

Despite numerous advantages, fluidized bed adsorption is limited in commercial applications due to a poor understanding of the relationships between mass transfer, hydrodynamics, and adsorption. To obtain a better understanding of these parameters, we used two commercially available resins to compare the adsorption of lysozyme as a function of bed expansion and bulk-phase viscosity using frontal analysis. Under static conditions adsorption was well represented by a Langmuir isotherm. Dynamic capacities at breakthrough were measured and normalized relative to the equilibrium capacity of each resin to facilitate direct comparison of resin performance under each condition. To quantify the impact of resin characteristics in expanded bed adsorption, we carried out a comparison of mass-transfer effects using a macroporous resin, Streamline SP, and a hyper-diffusive resin, S-HyperD LS. Both resins are designed for fluidized bed adsorption of proteins. In this study the results of frontal analysis showed that breakthrough was due to mass-transfer limitations of the adsorbing particles at expansions of 2 times the settled bed height. At expansions of 3 and 4 times the settled bed height, axial dispersion increased significantly; however mass-transfer limitations were still the dominant mechanistic feature contributing to early breakthrough at reduced dynamic capacity. Adsorption capacity under all conditions in this study was poorer for the macroporous resin than for the hyper-diffusive resin due to intraparticle mass-transfer limitations.

In this study, solid-phase adsorption by macroporous and hyper-diffusive resins was investigated in a batch uptake adsorption system to quantify solid-phase diffusion rates as a function of bulk phase viscosity. The performance of chromatographic resins used for adsorption of proteins is dependent on several factors including solid and liquid-phase diffusivity, boundary layer mass transfer, and intraparticle mass transfer effects. Understanding these effects is critical to process development and optimization of both packed and fluidized bed adsorption systems. The macroporous resin used here was Streamline SP, and the hyper-diffusive resin was S-HyperD LS. Both have been frequently used in fluidized bed adsorption of proteins; however, factors that affect uptake rates of these media are not well quantified. Adsorption isotherms were well represented by an empirical fit of a Langmuir isotherm. Solid-phase diffusion coefficients obtained from simulations were in agreement with other models for macroporous and hyper-diffusive particles. S-HyperD LS in the buffer system had the highest uptake rate, but increased bulk phase viscosity decreased the rate by approximately 50%. Increases in bulk phase viscosity increased film mass transfer effects, and uptake was observed to be a strong function of the film mass transfer coefficient. Uptake by Streamline SP particles was slower than S-HyperD in buffer, due to a greater degree of intraparticle mass transfer resistance. The effect of increased film mass transfer resistance coupled with intraparticle mass transfer resistances at an increased bulk phase viscosity resulted in a decrease of 80% in the uptake rate by Streamline SP relative to S-HyperD.

Stacks of 600 μm pellicles were exposed to the 4.6 and 3.0 GeV pion beam of the Berkeley Bevatron. A number of heavy unstable particles and hyperfragments were obtained. The ratio of the frequency of occurrence of K+and K--mesons has been found to be approximately unity in contrast to the large positive excess in the proton beam. As a possible explanation, it is suggested that the K--meson is produced in conjunction with a K+-meson according to the following reaction: π-+p → K++K-+N. Two hyperfragment decays of hydrogen have been fo nd in which the π--meson stops. One of the hyperfragments was identified as a 14H* produced by a ⌆--hyperon; the other one is a 13H* produced directly by the high energy pion. The range of all the charged particles was accurately determined which yielded a reliable value of the binding energy. The value of the binding energy (B.E.) for 13H* was found to be 1.2 ±0.6 and for 14H* B.E.(∧0) = 3.3 ±1. The mean free path for nuclear collisions was determined for 5.7 GeV protons and 3 GeV π-mesons. The results yielded for protons 37.6 ±5.3 cm and for π--mesons 35.5 ±5.0 cm. Both mean free paths are longer than the geometrical mean free path for nuclear collisions in the emulsion, which is 25 cm. Pacchi di pellicole di 600 μm sono stati esposti a fasci di protoni di 4.6 e 3.0 GeV del Bevatrone di Berkeley. Si sono ottenuti un certo numero di particelle instabili pesanti e di iperframmenti. Il rapporto della frequenza di produzione di mesoni K+e K-è risultato circa 1 in contrasto col grande eccesso positivo nel fascio protonico. Come possibile spiegazione del fenomeno si pensa che il mesone K-sia prodotto in unione con un mesone K+secondo la reazione π-+ p → K+K-+ N. Si sono trovati due iperframmenti da decadimento dell’idrogeno in cui si arresta il mesone π-. Uno degli iperframmenti è stato identificato con un 14H* prodotto da un iperone ⌆-; l’altro è un14H* prodotto direttamente dal pione di grande energia. Il percorso di tutte le parti celle cariche è stato accuratamente determinate, ottenendo un valore attendibile dell’energia di legame. Il valore dell’energia di legame (B.E.) per il 14H* risulta essere 1.2±0.6 e per il14H* B.E.(∧0) = 3.3±1-Il cammino libero medio per le collisioni nucleari è stato determinate per protoni di 5.7 GeV e per mesoni π-di 3 GeV. Si ottenne per i protoni 37.6 ±5.3 cm e per i mesoni π-35.5 ±5.0 cm. I due cammini liberi medi sono maggiori del cammino libero medio geometrico per collisioni nueleari in emulsione che è di 25 cm.