Journal Article

Orlistat-loaded solid SNEDDS for the enhanced solubility, dissolution, and in vivo performance

Ji, Yu-Geun, Kim, Dae Hun, Koo, Tae-Sung, Cho, Kwan Hyung, Kim, Rae Man, Kim, Jae Yeol, Maharjan, Pooja, Jang, Dong-Jin, Min, Kyoung Ah

2018

Overview

The present study aimed to develop orlistat-loaded solid self-nanoemulsifying drug delivery system preconcentrate (SSP) with the minimum use of lipid excipients for the enhanced solubility, in vitro dissolution, lipase inhibition, and in vivo performance. In the screening of solubilizing vehicles, Solutol HS15 and Lauroglycol 90 were selected as the surfactant and oil phase, respectively. A pseudo-ternary phase diagram composed of Solutol HS15, Lauroglycol 90, and orlistat as an anti-obesity agent and lipid component was constructed, and the SSP regions were confirmed in terms of the particle size distribution in water, melting point by differential scanning calorimetry, and crystallinity by X-ray diffraction. Physicochemical interaction between Solutol HS15 and orlistat resulted in SSP with various melting points in the range of 26°~33°C. The representative maximum orlistat-loaded SSP (orlistat/Solutol HS15/Lauroglycol 90=55/40/5, weight ratio) showed the melting point of 32.23°C and constructed uniform nanoemulsion with the particle size of 141.7±1.1 nm dispersed in water. In the dissolution test at pH 1.2 without any detergent, the SSP reached 98.12%±0.83% until 45 minutes, whereas raw orlistat showed no significant dissolution rate. The dissolution samples containing SSP showed a lipase inhibition of 90.42%±1.58% within 45 minutes. In terms of the reduction level of fat absorption in rats, the intake group of SSP gave a significantly higher fat excretion into stool than the one observed in the raw orlistat group ( <0.05). In conclusion, the suggested novel SSP formulation would be an effective and promising candidate for the treatment of obesity.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove Medical Press
• Subject: Administration, Oral / Animals / Anti-obesity agents / Bioavailability / Biological Availability / Calorimetry / Calorimetry, Differential Scanning / Detergents / Drug Delivery Systems / Drug dosages / Emulsions - chemistry / Excipients - chemistry / fat absorption / Feces - chemistry / Hypoglycemic agents / Lipase / Lipase - metabolism / lipase inhibition / Lipids / Lipids - chemistry / Lorcaserin / Male / Nanoemulsions / Nanoparticles - chemistry / Novels / Obesity / Oils - chemistry / Original Research / Orlistat / Orlistat - administration & dosage / Orlistat - chemistry / Orlistat - pharmacology / Particle Size / Pharmaceuticals / Phase Transition / Rats, Sprague-Dawley / solid self-nanoemulsifying drug delivery system / Solids / Solubility / Surface active agents / Surface-Active Agents - chemistry / Surfactants / Sus scrofa / Transition Temperature / Weight control / X-Ray Diffraction