This study reports a new technique for the manufacture of micron-sized, hollow crystals of a poorly water-soluble pharmaceutical compound, spironolactone, by a continuous and scalable antisolvent precipitation platform called a static mixer. Additives (polyvinylpyrrolidone (PVP) and Tween 80) were added during antisolvent precipitation to achieve the diffusion-limited growth condition required for the formation of hollow crystals. Over 90% of the products out of the total yield formed hollow crystals as adequate time was provided for crystal growth. PVP was found to be more effective in inducing hollow formation than Tween 80. The suspensions from antisolvent precipitation were subjected to freeze-drying or spray drying to obtain the final dried powder. The hollowness and morphology of the crystals were retained after freeze-drying and spray drying, although the crystallinity of the crystals was slightly reduced by the drying processes. The feasibility of applying such hollow crystals for oral and inhaled drug delivery was evaluated through in vitro dissolution study and aerosolization studies. The dissolution rate of spironolactone was significantly improved due to the high specific surface area of hollow crystals. In addition, a much improved aerosolization performance (similar to 3-fold increase) over the raw drug demonstrates the value and importance of hollow crystals in enhancing the performance of inhaled therapeutics.

• ASTAR
• National University of Singapore

• API

1. API
2. crystallization
3. Dissolution
4. Hollow structures
5. Precipitation
6. Research Article