Long-Term Physical Stability of Amorphous Solid Dispersions: Comparison of Detection Powers of Common Evaluation Methods for Spray-Dried and Hot-Melt Extruded Formulations.

Although physical stability can be a critical issue during the development of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect their physical stability. In this study, we have prepared fenofibrate ASDs using two representative manufacturing methods, hot-melt extrusion and spray-drying, to investigate their physical stability for one year. Intentionally unstable ASDs were designed to compare the detection power of each evaluation method, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and dissolution study. Each method did not provide the same judgment results on physical stability in some cases because of their different evaluation principles and sensitivity, which has been well-comprehended only for one-component glass. This study revealed that the detection powers of each evaluation method significantly depended on the manufacturing methods. DSC was an effective method to detect a small amount of crystals for both types of ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower compared to that of DSC, interpretation of the data was the easiest. SEM was very effective for observing the crystallization of the small amount of drug for hot-melt extruded products, as the drug crystal vividly appeared on the large grains. The dissolution performance of spray-dried products could change even without any indication of physical change including crystallization. The advantage/disadvantage and complemental roles of each evaluation method are discussed for deeper understanding on the physical stability data of ASDs.

Psychiatric disorders among patients undergoing hemodialysis therapy.

We examined the incidence rates of psychiatric disorders in end-stage renal failure patients on hemodialysis (HD) based on 4-year long-term follow-up. Among various psychiatric disorders, the frequency of three psychiatric disorders, dementia, delirium, and major depression, was relatively high. One-year incidence rate of whole psychiatric disorders was 10.6% (7.1% in non-aged and 13.7% in aged). One-year incidence rate of dementia in aged patients was 4.2% (dementia of the Alzheimer's disease, 0.5%; multi-infarct dementia, 3.7%). One-year incidence rate of multi-infarct dementia in aged HD patients was 7.4 times as large as that in the elderly general populations, suggesting that aged HD patients tend to exhibit multi-infarct dementia. The high incidence rate may be closely related to advanced arteriosclerosis and other medical conditions. Psychiatric management is required for ESRD patients with three major psychiatric disorders, dementia, delirium, and major depression, in particular for aged patients with multi-infarct dementia who has received long-term HD therapy.

A hemodialysis patient with trazodone-induced parkinsonism.

A hemodialysis male patient exhibited depressive symptoms and trazodone was prescribed orally. Although his depressive symptoms disappeared, he gradually presented with parkinsonism. His parkinsonism improved within a week after stopping trazodone. The clinical course strongly suggested that it was induced by trazodone. However, there is no report on antidopaminergic side effects of parkinsonism. This case suggests that antidopaminergic effects leading to parkinsonism need to be considered in patients on hemodialysis that are taking trazodone.