OBJECTIVES: To develop and optimize the novel self-microemulsifying drug delivery system (SMEDDS) formulation for enhanced water solubility and bioavailability of telmisartan (TMS) using the Box-Behnken design (BBD) and desirability function. METHOD: TMS-SMEDDS formulation consisted of the mixture of oil (Peceol), surfactant (Labrasol), co-surfactant (Transcutol), TMS and triethanolamine. A three-level BBD was applied to explore the main effect, interaction effect and quadratic effect of three independent variables, including the amount of Peceol (X1 ), Labrasol (X2 ) and Transcutol (X3 ). Determined conditions were 20 < X1 < 40, 50 < X2 < 80 and 5 < X3 < 30. The response variables were droplet size (Y1 ), polydispersity index (Y2 ) and dissolution percentage of TMS after 15 min (Y3 ). KEY FINDINGS: The optimized conditions were 28.93, 80 and 28.08 (mg) for X1 , X2 and X3 , respectively, and the response variables were predicted to be 159.8 nm, 0.241 and 85.8% for Y1 , Y2 and Y3 , respectively. The actual values from the optimized formulation showed good agreement with predicted values. The optimized TMS-SMEDDS formulation showed faster drug dissolution rate and higher bioavailability than TMS powder. CONCLUSIONS: Our results suggest that response surface methodology using BBD and desirability function is a promising approach to understand the effect of SMEDDS variables and to optimize the formulation.
OBJECTIVES: To develop and optimize the novel self-microemulsifying drug delivery system (SMEDDS) formulation for enhanced water solubility and bioavailability of telmisartan (TMS) using the Box-Behnken design (BBD) and desirability function. METHOD:TMS-SMEDDS formulation consisted of the mixture of oil (Peceol), surfactant (Labrasol), co-surfactant (Transcutol), TMS and triethanolamine. A three-level BBD was applied to explore the main effect, interaction effect and quadratic effect of three independent variables, including the amount of Peceol (X1 ), Labrasol (X2 ) and Transcutol (X3 ). Determined conditions were 20 < X1 < 40, 50 < X2 < 80 and 5 < X3 < 30. The response variables were droplet size (Y1 ), polydispersity index (Y2 ) and dissolution percentage of TMS after 15 min (Y3 ). KEY FINDINGS: The optimized conditions were 28.93, 80 and 28.08 (mg) for X1 , X2 and X3 , respectively, and the response variables were predicted to be 159.8 nm, 0.241 and 85.8% for Y1 , Y2 and Y3 , respectively. The actual values from the optimized formulation showed good agreement with predicted values. The optimized TMS-SMEDDS formulation showed faster drug dissolution rate and higher bioavailability than TMS powder. CONCLUSIONS: Our results suggest that response surface methodology using BBD and desirability function is a promising approach to understand the effect of SMEDDS variables and to optimize the formulation.
Authors: Yoon Tae Goo; Sangkil Lee; Ji Yeh Choi; Min Song Kim; Gi Hyeong Sin; Sun Ho Hong; Chang Hyun Kim; Seh Hyon Song; Young Wook Choi Journal: Drug Deliv Date: 2022-12 Impact factor: 6.819