A cross-sectional survey of methods for controling hand-foot syndrome in patients receiving capecitabine treatment.

Medical personnel actively provide patients taking capecitabine with information on the items to prevent and treat hand-foot syndrome (HFS). However, they are typically unable to ascertain the extent of patient compliance with the recommended items. Thus, the aim of the present study was to ascertain the association between patient compliance with preventative measures for HFS and the development of HFS. Subjects included 90 patients who were treated with a drug regimen that included capecitabine. Patients were treated at one of four facilities between July 2015 and January 2017. The main parameters studied were the extent to which items to prevent and treat HFS were (or were not) followed, and the associaiton between this extent and the development of HFS symptoms. A manual prepared by a pharmaceutical company that manufactures capecitabine describes 15 routine items to follow in order to prevent and treat HFS. The two activities patients most often performed were 'applying a moisturizer' (74.1%) and 'keeping one's skin clean (e.g., washing one's hands and feet)' (64.7%). The two activities patients least often performed were 'using sunscreen on exposed areas' (14.1%) and 'using soft insoles' (11.8%). Patients who performed more items to prevent and treat HFS were significantly less likely to develop symptoms of HFS (P=0.022). Based on these findings, it is recommended that medical personnel provide instructions to the patients regarding the specific items necessary to prevent and treat HFS, and to follow-up with the patients regarding their compliance, with an emphasis on the items they are less likely to take and on the instructions to avoid external irritants. Following these guidelines should lead to qualitative improvement in HFS management.

[Change in the drug release behavior of theophylline sustained-release tablets after division into two halves].

Dividing a tablet into two halves and providing them to patients is a routine approach in clinical practice. Obviously, the drug release behavior of tablets should be constant, regardless of the dividing process. Here, we investigated the change in drug release behavior after dividing tablets into two halves. Five commercial theophylline sustained-release tablets designed to be taken once a day were used as test tablets (two original products and three generic products). A 24 h dissolution test was performed for each tablet, and changes in drug release behavior were evaluated using similarity factors, f2, calculated from the drug release profiles. The drug release rates were substantially increased by dividing the tablets into two halves. Analysis of variance (ANOVA) revealed that the effect of the dividing process on drug release behavior was more significant than that of changing the products. We further observed the feature of cross sectioning of the surface of the tablets using a scanning electron microscope (SEM) and a laser-scanning microscope (LSM). The microscopic observations confirmed that the surface became rough and developed many cavities with the prolongation of the duration of the dissolution test. This study clarified that the division of tablets into two halves exerts significant effects on their drug release behavior, and may offer a profound insight into the proper use of pharmaceutical products.

A 5% glucose infusion fluid provokes significant precipitation of phenytoin sodium injection via interruption of the cosolvent effect of propylene glycol.

The precipitation of phenytoin sodium injection provoked by mixing with infusion fluids renders its use in clinical practice difficult, as rapid intravenous (i.v.) push and i.v. infusion are supposed to be avoided. As some of its aspects remain unclear, this study tried to elucidate this precipitation mechanism. In particular, this study focused on the significant precipitation induced by glucose infusion fluid. The precipitation provoked by 5% glucose infusion fluid was obviously different from the precipitation that accompanied simple pH reduction, in terms of the growth mode and morphology of crystals. In addition, the effect of glucose was partially unrelated to pH reduction. NMR measurements including a two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY) spectrum indicated the specific interaction between glucose and propylene glycol, which is incorporated into phenytoin sodium injection as a solubilizing agent. These results led to the conclusion that this interaction was crucial for the precipitation of phenytoin, as it diminished the solubilizing effect of propylene glycol, resulting in the enhancement of the crystallization of phenytoin. The determination of phenytoin solubility in aqueous solutions at different pH values revealed that phenytoin incorporated in the admixture could be dissolved completely, as long as the injection was diluted with saline or water. These findings offer a profound insight into the formulation design of phenytoin sodium injection and its use in clinical practice.