Effect of polymer species and concentration on the production of mefenamic acid nanoparticles by media milling.

The effect of four structurally different polymer species (hydroxypropylcellulose, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer and polyvinyl alcohol) on the production of mefenamic acid nanoparticles during media milling has been studied. It was found that product particle sizes are strongly determined by the type of polymeric stabiliser as well as by its concentration at constant process conditions. With respect to small product particle sizes an optimum excipient concentration was identified and adjusted for colloidal stability of the drug nanosuspensions. Furthermore, it was found that overdosing of excipients must be omitted to suppress ripening due to enhanced solubilisation phenomena. Hence, the smallest product particle sizes were obtained using a polymeric stabiliser which exhibits a high affinity to the model drug compound and a low solubilisation capacity. Affinities of each polymer species to mefenamic acid and corresponding surface concentrations were determined using straightforward and simple viscosity measurements of the supernatant. A relationship between polymer affinity, solubilisation capacity and limiting product particle size has been observed, which supports the hypothesis that final product particle sizes are rather determined by the solid-liquid equilibrium than by pure mechanical fracture.

Prediction of recrystallization behavior of troglitazone/polyvinylpyrrolidone solid dispersion by solid-state NMR.

The purpose of this study was to elaborate the relationship between the (13)C CP/MAS NMR spectra and the recrystallization behavior during the storage of troglitazone solid dispersions. The solid dispersions were prepared by either the solvent method or by co-grinding. The recrystallization behavior under storage conditions at 40 degrees C/94% RH was evaluated by the Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation. Solid dispersions prepared by the solvent method or by prolonged grinding brought about inhibition of the nucleation and the nuclei growth at the same time. No differences in the PXRD profiles were found in the samples prepared by the co-grinding and solvent methods, however, (13)C CP/MAS NMR showed significant differences in the spectra. The correlation coefficients using partial least square regression analysis between the PXRD profiles and the apparent nuclei-growth constant or induction period to nucleation were 0.1305 or 0.6350, respectively. In contrast, those between the (13)C CP/MAS NMR spectra and the constant or the period were 0.9916 or 0.9838, respectively. The (13)C CP/MAS NMR spectra had good correlation with the recrystallization kinetic parameters evaluated by the KJMA equation. Consequently, solid-state NMR was judged to be a useful tool for the prediction of the recrystallization behavior of solid dispersions.

Characterization and quantitation of clarithromycin polymorphs by powder X-ray diffractometry and solid-state NMR spectroscopy.

Characterization of clarithromycin polymorph was performed by solid-state cross polarization and magic angle spinning (CP/MAS) 13C-NMR spectroscopy. Two polymorphs, form II and form I, of clarithromycins indicated characteristic resonances of C1 carbonyl carbon at 176.2 and 175.2 ppm, respectively. Since each peak of C1 carbon was well separated in the spectrum of the two polymorphs, we performed quantitative analysis of the polymorphic fraction from the peak area of these peaks. The peak area of form I was found to linearly increase with an increase of its content, with a correlation coefficient of above 0.99. Solid-state NMR was found to be a useful technique to determine the characteristics of the polymorphic forms.