Orodispersible films (ODF) have clinical potential as extemporaneous pharmacy preparations for individualized pharmacotherapy. However, the conventional method of ODF preparation using a film applicator may limit its application, due to content uniformity challenges arising from viscosity changes of the casting solution and varied operator manipulation. This study proposes the unit-dose (UD) plate as an alternative to the film applicator for compounding individual ODFs. Using a design-of-experiments approach, we developed an extemporaneous ODF formulation for an antiemetic drug, ondansetron hydrochloride dihydrate (OND), at a clinically relevant dose. ODFs cast with the UD plate showed excellent content uniformity independent of the viscosity of the casting solution and drug concentration. Formulations were evaluated for performance with respect to patient acceptability and product quality. The effects of critical process parameters on critical quality attributes of the ODF were studied. HPMC concentration and volume of casting solution were the main factors affecting disintegration time and mechanical properties of the film, while drug concentration had no significant effect. However, further studies incorporating different drugs in larger concentration ranges are needed to investigate the impact of drug concentration and to establish a design space. Nevertheless, our results indicate the potential of using the UD plate to prepare ODFs with customized drug doses from a generic casting solution. Results from this study provide a framework for an extemporaneous ODF platform.