Analysis of Factors Related to Variation in Dissolution Profiles Estimated from Continuously Conducted Dissolution Tests of Generic Products.

The development of generic pharmaceuticals involves a bioequivalence study to ensure the therapeutic equivalence of the test formulation to the original innovative product. The formulation characteristics of generic products are expected to be maintained in the long term after approval. This study analyzed the factors contributing to the changes in the dissolution profiles of approved products during their life cycles. Cumulative data on the dissolution similarity of 1675 products of 127 ingredients tested by official laboratories in Japan were assessed according to Japanese bioequivalence guidelines with slight modifications. The products showing dissimilarities in dissolution profiles were analyzed for reporting year, therapeutic category, co-development, physical properties of the active pharmaceutical ingredient (API), and suspected reasons for dissolution change. The increase in the number of dissimilar products is related to the co-development of generic products. Although the solubility of the API was not associated with the dissolution change in the analysis of the total dissolution data, control of the API particle size is suggested to be important for drugs with poorly soluble APIs. Additionally, a risk factor for dissolution changes in the test solutions at a certain pH was the presence of acidic or basic residues. These results indicate the importance of proper development through a thorough evaluation of the formulation and process factors affecting the dissolution properties throughout the product lifecycle.

A Pilot Study to Develop a New Method of Assisting Children in Taking Their Medication by Using Immersive Virtual Reality.

Taking bitter-tasting drugs can be stressful for children who have underdeveloped swallowing skills and do not understand the meaning of medication. Furthermore, the senses of vision and smell are known to majorly influence taste. This pilot study was aimed at determining the effect of visual stimulation by immersive virtual reality (iVR) on taste and the safety of this approach for developing a new method to assist children with taking medication. Ten subjects participated in this study, and their mean (standard deviation (S.D.)) age was 21.8 (0.8) years. The subjects tasted the bitter aqueous solution (quinine 0.00375%) while viewing two different VR images (strawberry sponge cake and orange juice) alternately and received sensory tests immediately after the tasting and again 30 s later. In addition, nausea was assessed 30 s after tasting for each VR image. The primary endpoint was the difference in sensory test scores immediately after the tasting and 30 s later, between the two images. There were no significant differences in the sensory test scores between the placebo and either strawberry sponge cake or orange juice immediately after tasting. However, 30 s after tasting, the scores changed significantly to a tendency to perceive sweetness from the strawberry sponge cake and orange juice images compared with the placebo. No subject experienced nausea. Therefore, the findings of this study suggest that displaying images of sweet foods by using iVR to stimulate visual perception could safely reduce the sense of bitterness.

Is a Combination of Six Clinical Tests Useful as a Measure to Predict Short-Term Prognosis in Terminal Cancer Patients? A Prospective Observational Study in a Japanese Palliative Care Unit.

Background: To address the need for short-term prognostic methods using objective measures, we developed a method to predict a 2- or 3-week prognosis using only six clinical tests (known as the WPCBAL score). However, the method has not yet been directly compared with globally accepted prognostic methods. Objectives: This study aimed to clarify the usefulness of the WPCBAL score by comparing it with other prediction methods. Setting/Subjects: A prospective observational study was conducted with patients admitted to the palliative care unit of a Municipal Hospital in Japan between November 2017 and May 2021. Measurements: The primary endpoint was each prediction method's accuracy-the WPCBAL score, Glasgow Prognostic Score (GPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP), Delirium-Palliative Prognostic Score (D-PaP), and Prognosis in Palliative Care Study predictor models (PiPS-A, PiPS-B)-in predicting a prognosis at 2 or 3 weeks. The secondary endpoints were sensitivity, specificity, positive and negative predictive values, area under the receiver operating characteristic curve, and each prediction method's feasibility rate. Results: In total, 181 patients were included in this study. For the 3-week prognosis, the PaP had the highest accuracy (0.746), followed by the D-PaP (0.735), WPCBAL (0.696), PPI (0.652), and GPS (0.575). For the 2-week prognosis, the PiPS-B had the highest accuracy (0.702), followed by the WPCBAL (0.696) and PiPS-A (0.641). Conclusions: The WPCBAL score's accuracy in predicting a 2- or 3-week prognosis was comparable to that of commonly used prognostic methods, thus suggesting its usefulness as a short-term prognostic method.