Abstract
Liposomes prepared by a freeze-drying technique in the presence of mannitol have proved to be echogenic. However, the mechanism of echogenicity is not well understood. Here, we attempt to explain it. It was observed that only freeze-dried mannitol (without lipids) generates a strong scattered response because it generates bubble upon dissolution in water. The bubble generation was confirmed optically under an optical microscope. During the dissolution of the crystalline mannitol, the concentration of mannitol becomes locally very high. As the solute (mannitol) concentration increases, the saturated dissolved gas concentration decreases. Therefore, the dissolved gas in the solution near the dissolving crystal is in a supersaturated state. Upon sufficient supersaturation, bubble nucleation takes place. We found that freeze-dried crystalline excipients such as mannitol facilitate bubble nucleation compared to freeze-dried glassy excipient such as trehalose because of differences in surface morphology.
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