Background: Over the last few years, nanocrystal technology has expanded to improve the bioavailability of poorly water-soluble drugs, which is challenging. Nanocrystals (NCs) exhibit many properties, such as enhancing drug solubility, dissolution, oral absorption, and high drug loading. Ondansetron hydrochloride (ONH) is an antiemetic drug that antagonizes a serotonin 5-HT3 receptor in the peripheral and central nervous system and is widely prescribed for the management of chemotherapy and radiotherapy-induced vomiting and nausea, as well as for postoperative nausea. ONH exhibits approximately 60% bioavailability due to its poor solubility and first-pass metabolism in the liver. Its solubility is pH-dependent, its precipitates above pH 6. Objective: Preparation of ONH-NCs to increase its dissolution rate as a preliminary study to be prepared as a sublingual film to avoid first-pass metabolism. Method: NCs were prepared using the nanoprecipitation method and optimized via a D-optimal surface design considering drug to stabilizer ratio, solvent to anti-solvent ratio, stirring rate, and stabilizer type. Results: The process yielded particle sizes (PS) ranging from 99-409 nm and a polydispersity index (PDI) range of 0.08-0.44 using stabilizers such as Soluplus®, Brij 35®, and Kollidon VA 64® (Koli 64). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated showed reduced crystallinity, while Fourier transform infrared (FTIR) spectroscopy confirmed drug-stabilizer compatibility, and Field Emission Scanning Electron Microscopy (FESEM) depicted its morphological characterization. Conclusion: The results revealed that nanocrystallization of ONH may enable faster drug release at pH 6.8.
