Design and Evaluation of SMEDDS to Enhance Solubility and Dissolution of Anticancer Drug Using Modified Cylinder Method

作者：Khalid Nayab^*; Rahman Nisar U^*; Lobenberg Raimar; Akhtar Muhammad; Sarfaraz Muhammad K; Hajjar Bra'a M

来源：Latin American Journal of Pharmacy, 2017, 36(4): 647-657.

• DDSolver (R)
• dissolution
• etoposide
• modified cylinder method
• SMEDDS

In current study self-microemulsifying drug delivery system (SMEDDS) was developed with the aim to enhance solubility and dissolution of poorly water soluble drug etoposide. Two SMEDDS formulations were made with and without co-surfactant. In first formulation the medium chain triglycerides, polyoxyethylene sorbitan monooleate-20, and diethylene glycol monoethyl ether were used as oily vehicle, surfactant and solubilizer, respectively. While propylene glycol monolaurate type-I was incorporated additionally in second formulation, as co-surfactant. Optimized formulation (FL1D) was found comprising medium chain triglycerides as an oily vehicle (10%), polyoxyethylene sorbitan monooleate-20 (45%) as a major surfactant, diethylene glycol monoethyl ether (22.5%) as solubilizer, propylene glycol monolaurate type-1 (22.5%) as an additional co-surfactant. Phase diagram was used to identify microemulsion area. Dissolution studies were employed using a modified cylinder method. Dilution study was performed to check transparency using water, buffer (pH 4.6), SGF (Simulated Gastric Fluid) and SIF (Simulated Intestinal Fluid). FL1D showed small globule size 15.89 +/- 0.21 nm, zeta potential -12.9 +/- 0.03 mV and PDI 0.11 +/- 0.01. In dilution study the formulations F1-F3 and FL1-FL3 were found transparent. During the thermodynamic stability study F3 formulation became unstable. The % drug release of FL1D was 1.6 and 1.4 folds more than VePesid (R) capsule 50 mg in SIF and SGF, respectively. The optimized SMEDDS formulation presented almost entire drug release in 20 min in SIF while 40 min in SGF, respectively as compared to VePesid (R) that showed limited dissolution rate. The SMEDDS was developed successfully and results revealed an increase dissolution and solubility of etoposide that might increase its bioavailability.

• 出版日期2017