Nanoparticulation of probucol, a poorly water-soluble drug, using a novel wet-milling process to improve in vitro dissolution and in vivo oral absorption

• Published in: Drug development and industrial pharmacy Vol. 38; no. 8; pp. 1015 - 1023
• Main Authors: Tanaka, Yusuke, Inkyo, Mitsugi, Yumoto, Ryoko, Nagai, Junya, Takano, Mikihisa, Nagata, Shunji
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.08.2012; Taylor & Francis
• Subjects: Absorption; Administration, Oral; Animals; Drug Compounding - methods; Gelcire; Male; Nanoparticle; Nanoparticles - administration & dosage; Nanoparticles - chemistry; nanotechnology; Particle Size; Pluronic; Powders - chemistry; Probucol - administration & dosage; Probucol - chemistry; Probucol - pharmacokinetics; Rats; Rats, Wistar; Solubility; vitamine E-TPGS; Water - chemistry
• ISSN: 0363-9045; 1520-5762
• DOI: 10.3109/03639045.2011.637051

To improve the dissolution and oral absorption properties of probucol, a novel wet-milling process using the ULTRA APEX MILL was investigated. The particle size of bulk probucol powder was 17.1 µm. However, after wet-milling with dispersing agents such as Gelucire 44/14, Gelucire 50/13, vitamin E-TPGS, and Pluronic F-108, the probucol particle sizes decreased to about 77-176 nm. Scanning electron microscopy (SEM) analysis also suggested that the probucol particles were successfully milled into the nanometer range. An in vitro dissolution study showed that the dissolution rates of all nanopowders were several folds higher than those of the corresponding mixed powders. When orally administered to rats, the AUC values of probucol nanopowders treated with Gelucire 44/14 and 50/13, and vitamin E-TPGS were about 3.06-3.54-folds greater than that of the bulk powder. Therefore, through this study, we have developed a new pharmaceutical technique to improve the dissolution rate and oral absorption of probucol using the ULTRA APEX MILL by wet-milling with various dispersing agents.