Formulation and Evaluation of a Self-microemulsifying Drug Delivery System Containing Bortezomib

Abstract

The purposes of the present study were to develop a self-microemulsifying drug delivery system (SMEDDS) containing bortezomib, a proteasome inhibitor. The solubility of the drug was evaluated in 15 pharmaceutical excipients. Combinations of oils, surfactants and cosurfactants were screened by drawing pseudo-ternary phase diagrams. The system exhibiting the largest region of microemulsion was considered optimal. Bortezomib SMEDDS spontaneously formed a microemulsion when diluted with an aqueous medium with a median droplet size of approximately 20-30 nm. In vitro release studies showed that the SMEDDS had higher initial release rates for the drug when compared with the raw drug material alone. Measurement of the viscosity, size, and ion conductivity indicated that a phase inversion from water in an oil system to oil in a water system occurred when the weight ratio of the water exceeded 30% of the entire microemulsion system. In a pharmacokinetics study using rats, the bortezomib microemulsion failed to improve the bioavailability of the drug. The reason was assumed to be degradation of the drug in the microemulsion in the gastrointestinal tract. However, bortezomib in Labrasol(®) solution (an aqueous solution containing 0.025% Labrasol(®)) showed significantly increased area under the curve from 0-24 h (AUC0-24 h) and maximum plasma concentration (Cmax) values compared to the drug suspension. The findings of this study imply that oral delivery of a bortezomib and colloidal system containing Labrasol(®) could be an effective strategy for the delivery of bortezomib.

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Formulation and Evaluation of a Self-microemulsifying Drug Delivery System Containing Bortezomib
Eon-Pyo Hong,a,b,# Ju-Young Kim,c,# Su-Hyeon Kim,d Kyu-Mok Hwang,d Chun-Woong Park,e Hyo-Jung Lee,e Dong-Wook Kim,f Kwon-Yeon Weon,g Seo Young Jeong,*,a and Eun-Seok Park*,d
a College of Pharmacy, Kyung Hee University; Seoul 02447, Republic of Korea: b R&D Center, Handok Inc.; Seoul 02108, Republic of Korea: c College of Pharmacy, Woosuk University; Wanju-gun 55338, Republic of Korea: d School of Pharmacy, Sungkyunkwan University; Suwon 16419, Republic of Korea: e College of Pharmacy, Chungbuk National University; Cheongju 28644, Republic of Korea: f Department of Pharmaceutical Engineering, Cheongju University; Cheongju 28503, Republic of Korea: and g College of Pharmacy, Catholic University of Daegu; Gyeongsan 38430, Republic of Korea.
Received January 13, 2016; accepted April 6, 2016
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