[Administration of premedication with fexofenadine for paclitaxel-induced hypersensitive reactions in breast cancer patients complicated with closed-angle glaucoma].

Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed.

Crystallization of sucrose glass under ambient conditions: evaluation of crystallization rate and unusual melting behavior of resultant crystals.

Isothermal crystallization of sucrose glass under ambient condition was investigated by powder X-ray diffraction, isothermal microcalorimetry, and water sorption/desorption analysis. Isothermal microcalorimetry measurements showed that the crystallization behavior was affected by the compression force applied to starting amorphous materials. The crystallization rate was analyzed by X-ray diffraction measurements to establish that the rate could well be explained by the Avrami-Erofeev equation. In the water sorption/desorption analysis, the weight change during the crystallization was elucidated by supposing that desorption proceeded from the crystallized part. The sucrose crystallized at relatively low temperature conditions showed completely different melting behavior from that of intact sucrose, although the crystal form was most likely to be identical. This difference could be explained by defects in the lattice structure produced during the crystallization and the desorption process. Correlation was found between the melting temperature and the water content just before the crystallization. Defects in the crystal structure were partially modified by annealing as has been found in relaxation studies of amorphous materials.

Solubilization behavior of a poorly soluble drug under combined use of surfactants and cosolvents.

The solubilization behavior of a poorly soluble model drug, phenytoin (PHT), under combined use of surfactants (sodium dodecyl sulfate (SDS), Tween 80) and cosolvents (dimethylacetoamide (DMA), ethanol, poly(ethylene glycol) 400 (PEG), glycerol) was examined. The solubility of PHT in the aqueous surfactant solutions increased linearly with increase of the surfactant concentration. The solubility of PHT in water-cosolvent mixtures roughly followed the log-linear model, which is widely accepted to explain the solubilization behavior of poorly soluble compounds in water-cosolvent mixtures, except for the case of glycerol, in which the solubility was minimal at 10% (w/v) of glycerol. When the cosolvents were added to the aqueous surfactant solutions, their effect on the solubility depended on the combination of the surfactant and the cosolvent. The most striking increase in solubility was observed with DMA, regardless of the type of surfactant. When ethanol was added, an increase in the solubility was observed with the Tween 80 solution, while a dramatic decrease was found with the SDS solution. The addition of glycerol or PEG to the surfactant solutions had only a minor impact on the solubility. These solubilization behaviors of PHT in the surfactant-cosolvent mixtures were partially explained by the solubility model introduced in our previous paper [Kawakami, K., Miyoshi, K., Ida, Y., 2004. Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent. J. Pharm. Sci. 93, 1471-1479]. Addition of the cosolvents to the surfactant solutions generally offered only a small advantage from the viewpoint of improving solubility because of the decrease in the solubilization capacity of the micelles.

Impact of the amount of excess solids on apparent solubility.

PURPOSE: The impact of excess solids on the apparent solubility is examined. METHODS: The apparent solubility of some model drugs was measured in various buffered solutions, with various amounts of excess solid. To help understand the dependence of the solubility on the amount of solid, we evaluated the dissolution and crystallization rates of indomethacin (IDM), one of the model drugs, at near-equilibrium conditions. RESULTS: In the case of IDM, the apparent solubility decreased with an increase in the solid amount at pH 5 and 6. On the other hand, it increased with an increase in the solid amount at pH 6.5 and 7. The crystallization and dissolution rates of IDM decreased and increased, respectively, with an increase in pH values, and became equal at between pH 6 and 7. Therefore, the apparent solubility was most likely to be affected by the balance between the crystallization and dissolution rates. The apparent solubility of other model drugs showed the same trend, although the dependency on the solid amount was not as significant as in the case of IDM. CONCLUSIONS: The apparent solubility was affected by the amount of solid for all the model drugs investigated. This was most likely to be caused by a competition between the crystallization and dissolution rates.

Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent.

Gelucire 44/14 is a surface-active excipient that can solubilize poorly soluble drugs. We investigated its solubilization behavior when coexisting with dimethylacetoamide (DMA) or dimethylsulfoxide (DMSO), both of which are also expected to enhance drug solubility. Gelucire was confirmed to form micelles by surface tension and fluorescence measurements both in water and water/cosolvent mixtures. Light-scattering measurements revealed that DMA and DMSO affect the micellar morphology in a different manner. DMA helped form large structures by being entrapped in the hydrophobic region of the micelles and/or inducing the aggregation. DMSO was likely to be anchored to the interfacial layer and did not induce micelle growth. Two model drugs, phenytoin and indomethacin, were employed to observe the solubilization behavior of poorly soluble drugs in Gelucire/cosolvent mixtures. The solubility of these drugs in the mixtures could be explained very well by using the new solubility model introduced in this article. Addition of cosolvents to the Gelucire solution did not enhance the solubility very much, and thus the combined use of cosolvents with Gelucire offered only little advantage from the viewpoint of solubility.