Hydroxypropyl-ß-cyclodextrin-based solid dispersed granules: A prospective alternative to conventional solid dispersion.

The purpose of the present study was to develop hydroxypropyl-ß-cyclodextrin (HP-ß-CD)-based solid dispersed granules as a superior system to solid dispersion. The solid dispersed granules and solid dispersion were compared in terms of powder property improvement, solubility increment and oral bioavailability enhancement of poorly water-soluble dexibuprofen. Solid dispersion (drug/HP-ß-CD/Tween80 = 1:7:0.1, weight ratio) and solid dispersed granules (drug/HP-ß-CD/Tween80/Microcrystalline cellulose = 1:7:0.1:4) were fabricated using a spray-dryer and fluid bed granulator, respectively. The HP-ß-CD-based solid dispersed granules significantly improved solubility, dissolution profile and oral bioavailability of dexibuprofen compared to pure drug powder. Moreover, the solid dispersed granules maximised the oral bioavailability of dexibuprofen to the same extent as the solid dispersion. However, considerable improvements of powder and tablet properties were observed in solid dispersed granules as compared with solid dispersion. Therefore, HP-ß-CD-based solid dispersed granules would be a prospective alternative to solid dispersion.

Effect of molecular size of PEGylated recombinant human epidermal growth factor on the biological activity and stability in rat wound tissue.

The purpose of this study was to investigate the effect of size of polyethylene glycol (PEG) conjugated to recombinant human epidermal growth factor (rhEGF) on its stability in skin wound tissue and in vitro biological activity to find the desirable conjugate as topical therapeutic agent for wound healing. Site-specific PEGylation at N-terminus of rhEGF was performed with monomethoxy PEG-Butyraldehyde derivatives (MW 2, 5, and 20 kDa). Mono-PEG-rhEGFs retained 60-70% of biological activity of native rhEGF, and the effect of PEG size was not significant. The improvement of stability in the rat skin wound tissue was dependent on the increase of the PEG size attached. The degradation half-lives of native rhEGF, mono-PEG-2K-, -5K-, and -20K-rhEGFs were 1.1, 3.1, 5.2, and 41.5 hr, respectively. Therefore, mono-PEG-20K-rhEGF was considered to be the most desirable in terms of the increase of stability and the preservation of biological activity. This study suggests that the high molecular weight PEG at N-terminus of rhEGF would give a satisfactory stabilizing effect and thus may improve therapeutic efficacy in clinical use.