Nanoparticulation of probucol, a poorly water-soluble drug, using a novel wet-milling process to improvein vitrodissolution andin vivooral absorption

Abstract

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.

Novel chenodeoxycholic acid–sodium alginate matrix in the microencapsulation of the potential antidiabetic drug, probucol. Anin vitrostudy

“…It is clear that CDCA provided enhanced resistance to mechanical strength as well as osmoticinduced swelling, and thus PB uniphasic release in the presence of CDCA can be explained by its accumulation on the surface of the microcapsules (shown in Figure 1) resulting in rapid initial loss of surface-bound PB and this was illustrated in the first significantly visible peak ( Figure 6). Such release may optimize PB-targeted delivery at the lower part of the gut, where most of its absorption is expected to take place and thereby optimizing its efficacy (Tanaka et al, 2012;Takka and Cali, 2012;Yamamoto et al, 1994). Figure 7 shows microcapsule morphological characteristics before and after accelerated stability testing.…”

Is the combination of cellulosic polymers and anionic surfactants a good strategy for ensuring physical stability of BCS Class II drug nanosuspensions?

“…One way for increasing the bioavailability of such drugs is to increase the surface area via formation of nanoparticles. Size reduction of drug crystals increases the specific surface area, which can improve the dissolution rate of drugs 3,4 according to the Noyes-Whitney equation 5 . To produce nanoparticles, wet stirred media milling (WSMM) has been commonly used in the pharmaceutical industry as it is continuous, scalable, solvent-free and environmentally benign [6][7][8][9] .…”

Optimizing nanomedicine pharmacokinetics using physiologically based pharmacokinetics modelling

“…SDNs are lipid-free nanoparticles which are used to improve the oral bioavailability and exposure of poorly water-soluble drugs (Chan, 2011;Tanaka et al, 2012). Constituents include drug and stabilizer, and SDNs are produced using a 'topdown' (high pressure homogenization and wet milling) or bottom-up (solvent evaporation and precipitation) approach .…”