Preparation and structural analysis of (±)-threo-ritalinic acid.

Hydrolysis of the methyl ester (±)-threo-methyl phenidate afforded the free acid in 40% yield, viz. (±)-threo-ritalinic acid, C13H17NO2. Hydrolysis and subsequent crystallization were accomplished at pH values between 5 and 7 to yield colourless prisms which were analysed by X-ray crystallography. Crystals of (±)-threo-ritalinic acid belong to the P21/n space group and form intermolecular hydrogen bonds. An antiperiplanar disposition of the H atoms of the (HOOC-)CH-CHpy group (py is pyridine) was found in both the solid (diffraction analysis) and solution state (NMR analysis). It was also determined that (±)-threo-ritalinic acid conforms to the minimization of negative gauche(+)-gauche(-) interactions.

Simultaneous quantification of polymeric and surface active stabilizers of nanosuspensions by using near-infrared spectroscopy.

Nanosuspension technology is an attractive approach for the formulation and solubility enhancement of poorly water-soluble drug compounds. The technology requires adequate excipients for stabilizing the suspensions during nanogrinding and storage. This study aimed at establishing a near-infrared (NIR) method for assaying simultaneously the two nanoparticle stabilizers, sodium dodecyl sulphate (SDS) and hydroxypropylcellulose (HPC), in miconazole nanosuspensions. Second derivative of NIR signals was used to establish calibration curves in concentration ranges of interest of SDS (0.03-0.3%) and HPC (0.75-7.5%). The suitability and applicability of the NIR method was verified by evaluating the linearity, accuracy, precision, and specificity of the obtained data. The method was then used to quantify indirectly the amount of SDS and HPC adsorbed onto miconazole nanoparticles. Within the concentration range of interest, SDS adsorption increased up to 122 µg/m(2) (4.2 × 10(-7) mol/m(2)) with increasing SDS concentration, and HPC adsorption was in the range of 800-1000 µg/m(2) (21-27 × 10(-7) mol/m(2)) for nanosuspensions containing nominally 5% HPC and 12.5% or 20% miconazole. Interestingly, some of the adsorbed HPC was displaced upon increase of SDS concentration and adsorption. The data were also confirmed by surface tension measurements of aqueous solutions of SDS and HPC and nanosuspension supernatants. The availability of a fast and nondestructive method for quantifying simultaneously the adsorption of two stabilizers onto nanoground particles may not only speed up nanosuspension development, but also provide insight into the mechanisms of nanoparticle stabilization regarding competitive adsorption and electrostatic versus steric stabilization.

Mechanistic aspects of molecular formation and crystallization of zinc oxide nanoparticles in benzyl alcohol.

Zinc oxide nanostructures are known to exist in a great variety of morphologies. However, the underlying mechanisms leading to these architectures are far from being fully understood. Here, we present a time dependent study of the generation of zinc oxide nanorods, which arrange into bundles with a fan- or bouquet-like structure, using the benzyl alcohol route. The structural evolution of the nanoparticles was monitored by electron microscopy techniques, whereas the progress of the chemical reaction was followed by quantification of the organic by-products using gas chromatography. With this study we give a detailed insight into the formation of the zinc oxide structures, which involves a complex pathway based on many in parallel occurring processes such as crystallization of primary particles, their oriented attachment and surface reconstruction inside the nanoparticulate agglomerates. However, in spite of such an intricate growth behavior, the ZnO nanostructures are surprisingly uniform in size and shape.