文献名： Enhanced Solubility, In-Vitro Dissolution and Lipase Inhibition of a Self-Nanoemulsifying Drug Delivery System Containing Orlistat

作者： Kim, Dae Hun¹; Maharjan, Pooja¹; Kim, Jae Yeol¹; Jang, Dong-Jin²; Koo, Tae-Sung³; Min, Kyoung Ah¹; Cho, Kwan Hyung¹

1: College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Republic of Korea

2: Department of Pharmaceutical Engineering, Inje University, Gimhae 50834, Republic of Korea

3: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of Korea

摘要：The aim of this work was to prepare and assess a self-nanoemulsifying drug delivery system (SNEDDS) containing water-insoluble orlistat that was used for the inhibition of lipase activity in gastrointestinal lumen. The pseudo-ternary phase diagram, composed of orlistat and medium chain triglycerides (MCT) as oil phase and Cremophor EL as surfactant, was made for the confirmation of giving SNEDDS preconcentrate. The physical state, particle size dispersed in water, dissolution and lipase inhibition of SNEDDS preconcentrates were investigated. The appointed SNEDDS preconcentrates in the pseudo-ternary phase diagram showed no endothermic peak of orlistat and a liquid state. The particle sizes of SNEDDS dispersed with water were uniform and in the range of <200 nm. In the dissolution test, the liquid SNEDDS preconcentrate and solid state mixture exhibited 90.89±2.03% versus 22.42±3.71% at 60 min., respectively, whereas the raw orlistat showed no significant dissolution rate. The SNEDDS preconcentrate showed a lipase inhibition of 92.42±1.58% until 60 min., with no significant inhibition activity of orlistat. Therefore, the SNEDDS preconcentrate presented in this work solubilized orlistat and increased its dissolution rate, and resulted in sufficient inhibitory action on lipase.