Long-term physical stability of amorphous solid dispersions: Comparison of detection powers of common evaluation methods for spray-dried and hot-melt extruded formulations

Kohsaku Kawakami; Taichi Ishitsuka; Masafumi Fukiage; Yohei Nishida; Tetsuo Shirai; Yosuke Hirai; Tetsu Hideshima; Fumiaki Tanabe; Koji Shinoda; Ryota Tamate; Takuya Fujita

doi:10.1016/j.xphs.2024.06.020

論文 Long-term physical stability of amorphous solid dispersions: Comparison of detection powers of common evaluation methods for spray-dried and hot-melt extruded formulations

Kohsaku Kawakami ; Taichi Ishitsuka ; Masafumi Fukiage ; Yohei Nishida ; Tetsuo Shirai ; Yosuke Hirai ; Tetsu Hideshima ; Fumiaki Tanabe ; Koji Shinoda ; Ryota Tamate ; Takuya Fujita

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Kohsaku Kawakami, Taichi Ishitsuka, Masafumi Fukiage, Yohei Nishida, Tetsuo Shirai, Yosuke Hirai, Tetsu Hideshima, Fumiaki Tanabe, Koji Shinoda, Ryota Tamate, Takuya Fujita. Long-term physical stability of amorphous solid dispersions: Comparison of detection powers of common evaluation methods for spray-dried and hot-melt extruded formulations. Journal of Pharmaceutical Sciences. 2024, 114 (1), 145-156. https://doi.org/10.1016/j.xphs.2024.06.020

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(abstract)

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.

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