Abstract This study concerns a new antiretroviral drug named CRS 74, which has a limited bioavailability because of its low aqueous solubility and dissolution rate. To improve these properties, CRS 74 can be recrystallized by using Liquid Anti-Solvent (LAS) crystallization. Ethanol is chosen as the solvent under study for the molecule and water as the anti-solvent. Since solubility data is limited, it is necessary to collect experimental data for the molecule in relation to ethanol and water-ethanol mixtures at different temperatures in order to select suitable mixture compositions and temperature for LAS process design. In this work, the CRS 74 solubility measured in the temperature range 288.15 - 303.15 K in pure ethanol and in 95% water - 5% w/w ethanol mixtures, and the CRS 74 solubility measured at 303.15 K in water-ethanol mixtures containing from 30 to 70% w/w ethanol are presented. Measurements were performed using the shake-flask method for generating the saturated solutions followed by compositional analysis by HPLC of the solution. The experimental data showed that the solubility of CRS 74 in binary hydroalcoholic mixtures increases upon increasing the temperature and mass fraction of ethanol. In order to better understand the behavior of the system and to estimate supersaturation conditions for a larger range of CRS 74 crystallization conditions, two models have been chosen to describe the experimental data: UNIQUAC and Jouyban-Acree models. The modeling of experimental solid-liquid equilibrium data proved that both models could correlate satisfactorily the solubility of the studied drug. This study provided valuable data for the recrystallization of CRS 74 by using the Liquid Anti-Solvent (LAS) crystallization process.

This paper was devoted to studying the influence of coating material (nanocapsules or nanospheres), drug model (diclofenac, acid or salt) and method of preparation on the morphological characteristics of nanoparticle-coated microparticles. The cores of microparticles were obtained by spray drying or evaporation and the coating was applied by spray drying. SEM analyses showed nanostructures coating the surface of nanocapsule-coated microparticles and a rugged surface for nanosphere-coated microparticles. The decrease in their surface areas was controlled by the nanoparticulated system, which was not dependent on microparticle size. Optical microscopy and X-ray analyses indicated that acid diclofenac crystals were present in formulations prepared with the acid as well as in the nanocapsule-coated microparticles prepared with the salt. The control of coating is dependent on the use of nanocapsules or nanospheres and independent of either the characteristics of the drug or the method of preparing the core.

Chitosan microspheres of a small particle size and with good sphericity were prepared by a spray-drying method followed by treatment with a cross-linking agent. Owing to restrictions on the use of cross-linked chitosan microspheres in the pharmaceutical field, d,l-glyceraldehyde, a biocompatible reatant was used. The parameters studied affecting extent of cross-linking were cross-linking time and concentration of the cross-linking agent. Glutaraldehyde, the aldehyde most frequently employed as chemical cross-linking agent for proteins, was also used as a control. The cross-linked spray-dried chitosan microspheres were analyzed with respect to their morphological aspects, particle size, zeta potential and water uptake capacity. It was found that an increase either in d,l-glyceraldehyde concentration or in duration of cross-linking caused a decrease in both the swelling capacity and the zeta potential of the chitosan microspheres. Compared to glutaraldehyde, d,l-glyceraldehyde appears to be a good cross-linking agent for chitosan microspheres with the advantage that it is nontoxic.

Unloaded microspheres were prepared from polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-valerate (PHB-HV) polymers using an oil-in-water emulsion solvent evaporation method. The study was conducted to evaluate how the polymer and some process parameters affect properties of the final microspheres such as particle size, superficial area, zeta potential, surface morphology and microsphere degradation. The variables included surfactant concentration in the emulsion water phase and solvent composition. From the results, it was found that the parameters affecting microsphere size the most were surfactant concentration in the emulsion water phase and solvent composition. Properties such as zeta potential, surface area and surface morphology remained pratically unchanged over the range of the processing conditions studied here.