Development and in vitro characterization of novel self-emulsifying formulations of LOW-solubility active pharmaceutical ingredient

Most of the newly developed drug candidates have low solubility in water, which causes low oral bioavailability. There are many techniques in the literature to overcome poor bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) are a successful technique to improve the bioavailability of low-soluble drugs. Aprepitant, a drug that is the first member of the NK1 receptor antagonists with a different mechanism of action, was selected as a model drug with low solubility. It is an indispensable drug that is recommended as a first-line drug by important treatment guidelines. It was aimed to increase the oral bioavailability of aprepitant by preparing it as a SNEDDS formulation. Firstly, excipients were selected. The selection was made by considering the solubility of aprepitant and emulsification efficiency of the excipients. Pseudo-ternary phase diagrams were prepared to find the appropriate ratios of the selected excipients in the formulation. Type-III or Type-IV formulations were prepared as liquid, solid or semi-solid states. Supersaturated-SNEDDS were prepared to increase the amount of aprepitant that can be loaded into the formulations. Various polymers were added to supersaturated-SNEDDS to extend the precipitation time of the aprepitant. Liquid formulations were converted into powders by using porous adsorbents. Semi-solid formulations were filled into hard gelatin capsules while they were molten. Droplet size and zeta potential measurement, lipolysis test, dissolution test, cytotoxicity studies were performed on the prepared formulations. After the optimized formulation was determined, additional characterization studies such as FT-IR, DSC, XRPD analysis and stability tests were performed. Finally, in vivo bioavailability study was carried out in rats. It was found that the bioavailability of the optimized formulation was 2.3 fold of the aprepitant suspension.