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Abstract: The crystallization process in aqueous solutions of the drug bicalutamide and the effect of the polymer polyvinylpyrrolidone (PVP) have been studied. Results showed that PVP decreased the crystallization rate significantly in a system with PVP concentrations as low as 0.01% (w/w), without changing the polymorph formed. The crystal habit was altered already at PVP concentrations as low as 0.001% (w/w). Measurements made with self-diffusion NMR indicated that the decrease in crystallization rate was not because of a reduced supersaturation due to bicalutamide binding to PVP in solution. Furthermore, in experiments designed to specifically study crystal nucleation, the same nucleation rate was found in the absence and presence of PVP. Instead, PVP adsorbs to the crystals formed in solution and by doing so, the crystal growth rate is reduced. This was confirmed in separate experiments using bicalutamide nanocrystals. By combining theories describing classical nucleation and crystal growth, with some modifications, a consistent description of several independent experiments performed in polymer-free systems was obtained. From these experiments a crystal–water interfacial tension of 22.1 mN/m was extracted. We also analyze the interfacial tension of other crystalline organic solids and find that it varies approximately as the logarithm of the solubility. This finding is discussed within the framework of the Bragg–Williams regular solution theory where we also compare with the tension of liquid alkanes. [Copyright &y& Elsevier]

Abstract: The pharmacokinetic parameters of AZ68 administered as a solution have been compared with those from an amorphous and a crystalline nanosuspension using rats as in vivo specie. All formulations were administered intravenously (i.v.) and orally. The purpose of the study was to find out if the three different formulations were comparable and safe to administer. The results indicate that AZ68 is absorbed at a lower rate for crystalline nanosuspensions compared to amorphous nanosuspensions and solutions. However, the absorbed extent of the compound is similar. The results are a consequence of the lower solubility and the slower dissolution rate for crystalline material compared to amorphous substance in the gastrointestinal tract. The dissolution process is excluded for a solution, resulting in the fastest absorption rate. No significant difference was found between pharmacokinetic parameters when comparison was made between the formulations after i.v. administration. There were no adverse events observed after i.v. administration of the nanosuspensions. [Copyright &y& Elsevier]