Oral self-emulsifying drug delivery systems, from biopharmaceutical to technical formulation aspects

Self-emulsifying drug delivery systems can include a broad range of oils, surfactants and co-solvents. A spontaneous fine emulsion or micro-emulsion is formed in contact with water or gastro-intestinal fluids. There is a growing interest in this pertinent drug delivery approach and a key rationale is to formulate biopharmaceutically challenging drugs. In this review, a structured method is presented for how oral self-emulsifying formulations can be developed. The screening of drug solubility in excipients and the study of phase behavior are discussed in the first step. This initial development phase should also consider the known biological effects of selected excipients. Following the identification of candidate formulations, different in vitro tests are performed to mimic the fate of the formulation in vivo. The early dilution and dispersion tests can run in parallel on a small scale to primarily characterize the systems and to screen for unfavorable phase separation or precipitation of the drug. At a later stage, compendial equipment is used and dynamic lipolysis testing can provide valuable information about the digestion of the formulation. The next step is the performance evaluation of selected formulations in animals. Finally, technical aspects of different capsule and filling technologies are addressed in order to connect the early biopharmaceutical considerations with aspects of the dosage form manufacture.