Tailoring the release rates of fluconazole using solid dispersions in polymer blends.

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.

Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation.

The physical structure and polymorphism of nimodipine were studied by means of micro-Raman, WAXD, DSC, and SEM for cases of the pure drug and its solid dispersions in PEG 4000, prepared by both the hot-melt and solvent evaporation methods. The dissolution rates of nimodipine/PEG 4000 solid dispersions were also measured and discussed in terms of their physicochemical characteristics. Micro-Raman and WAXD revealed a significant amorphous portion of the drug in the samples prepared by the hot-melt method, and that saturation resulted in local crystallization of nimodipine forming, almost exclusively, modification I crystals (racemic compound). On the other hand, mainly modification II crystals (conglomerate) were observed in the solid dispersions prepared by the solvent evaporation method. However, in general, both drug forms may appear in the solid dispersions. SEM and HSM microscopy studies indicated that the drug particle size increased with drug content. The dissolution rates were substantially improved for nimodipine from its solid dispersions compared with the pure drug or physical mixtures. Among solid dispersions, those resulting from solvent coevaporation exhibited a little faster drug release at drug concentrations lower than 20 wt%. Drug amorphization is the main reason for this behavior. At higher drug content the dissolution rates became lower compared with the samples from melt, due to the drug crystallization in modification II, which results in higher crystallinity and increased particle size. Overall, the best results were found for low drug content, for which lower drug crystallinity and smaller particle size were observed.

Variable Coordination and Conformation of the 3-Cyano-2,4-pentanedionato Anion in a Mixed-Ligand Binuclear Copper(II) Chelate.

The addition of dipyridylamine to bis(3-cyano-2,4-pentanedionato)copper(II), Cu(NC-acac)(2), induces changes in the mode of interaction and the conformation of the NC-acac(-) anion. The structure of the resulting binuclear compound was determined from a single microcrystal (monoclinic, space group P2(1), a = 7.894(7) Å, b = 25.550(24) Å, c = 11.661(13) Å, beta = 106.10(8) degrees, Z = 2, R(1) = 0.0564, (w)R(2) = 0.1197). In the addition compound {[Cu(NC-acac)dipyamH](NC-acac)}(2) when the NC-acac(-) acts as a chelating and bridging ligand, it assumes the commonly observed U(Z,Z) conformation, while behavior as weakly N-coordinated unidentate counteranion imposes the rarely encountered S(Z,E) conformation. In the [Cu(NC-acac)dipyamH](NC-acac)] entities one of the copper(II) centers is a 4 + 2 Jahn-Teller complex while the other is a square-based pyramid.