Machine learning guided optimization of an oral microemulsion system: a Bayesian optimization approach

Abstract Oral microemulsions are one drug delivery system often implemented to improve intestinal permeability and oral bioavailability of poorly water-soluble drugs. They also present several practical advantages including high patient compliance and simplified manufacturing methods which contribute to their promise as marketable drug products. Despite these advantages, however, the microemulsion formulation development process is extremely time consuming and resource intensive, typically involving extensive screening of components and excessive preliminary trials in order to achieve stable formulations. As a result, MEs are often suboptimal in their therapeutic performance, and there is an unmet need for improved methods to streamline microemulsion formulation design. In this work, a batch Bayesian Optimization strategy was used to design a subset of unique in-specification microemulsions with highly optimized physicochemical properties in five iterations containing batches of five experiments. A two-phase modeling approach was developed to achieve this goal and allowed for navigating a complex experimental design space, including multiple oils, surfactants, cosurfactants, and processing parameters with an initial training dataset consisting of 22 experiments. As a result of this study, five high-performing blank microemulsions were identified, and four of them exhibited physical stability upon storage for up to 30 days. Further, when loaded with two different model drug candidates, three of the microemulsions achieved high drug loading, acceptable stability and improved in-vitro permeability, highlighting their promise for potential translation to later stages of development.