Hydrotropic solubilization of poorly soluble drugs
Abstract
The purpose of the present study is to develop a good solubilization vehicle for various poorly soluble drugs via hydrotropic solubilization. To achieve this goal, we discovered a new hydrotrope, DMBA and it showed more than 1000-fold solubility enhancement of 13 poorly soluble compounds which have a broad range of hydrophobicity. A new hydrotropic polymer micelle, PEG-b-PVBODMBA containing DMBA as a hydrophobic core showed higher probucol loading content, higher solubility enhancement of various poorly soluble drugs, and higher physical stability in blood plasma than the previous hydrotropic polymer micelle, PEG-b-PVBODENA. Structural analysis and SIMCA multivariate analysis suggest that the number of aromatic rings may be the most effective property to the hydrotropic solubilization. And this characteristic of hydrotropes as a solubilizer is more effective when it existed as micelles in water after polymerization due to highly localized hydrotropic concentration inside of hydrophobic core of micelles. Our two hydrotropic polymer micelles, PEG-b-PVBODENA and PEG-b-PVBODMBA showed similar or much higher drug loading contents than the conventional polymer micelle, PEG-b-PLA. The mixed micelle composed of 50:50 PEG-b-PVBODENA and PEG-b-PVBODMBA showed higher drug loading contents than PEG-b-PLA and individual hydrotropic polymer micelles. Especially it loaded paclitaxel more than 53.1 % (w/w). High drug loading capacity of mixed hydrotropic polymer micelles for various hydrophobic drugs strongly suggests that they can be a good candidate as a universal solubilization vehicle.
Degree
Ph.D.
Advisors
Pinal, Purdue University.
Subject Area
Pharmacy sciences
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.