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Amorphous solid dispersions (ASDs) play a key role in the pharmaceutical industry through the use of high-energy amorphous state to improve solubility of pharmaceutical agents. Understanding the physical stability of pharmaceutical glasses is of great importance for their successful development. We focused on the anti-HIV agent, ritonavir (RTV), and investigated the influence of annealing at temperatures below the glass transition temperature (sub-T) on physical stability, and found that the sub-T annealing effectively stabilized RTV glasses. Through the atomic structure analyses using X-ray pair distribution functions and infrared spectroscopy, we ascertained that this fascinating effect of the sub-T annealing originated from strengthened hydrogen bonding between molecules and probably from a better local packing associated with the stronger hydrogen bonds. The sub-T annealing is effective as a physical stabilization strategy for some pharmaceutical molecules, which have relatively large energy barrier for nucleation.

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A 77-year-old man was referred to our hospital for abnormal thoracic radiographs. Computed tomography (CT) revealed a 20-mm subpleural ground-glass opacity in the right S 6 area. A CT-guided biopsy revealed lung adenocarcinoma. Fluorodeoxyglucose-positron emission tomography revealed multiple abnormal bone accumulations, and a subsequent biopsy of a left iliac bone lesion revealed chronic lymphocytic leukemia. A right lower lung lobectomy was performed for the lung adenocarcinoma (cT1bN0M0, stage IA2). An aggressive biopsy of the bone lesion confirmed a rare case of double primary malignancies, which determined the patient's treatment and outcomes.