Exploring Vitamin E‐Based Glycosides, Novel Surfactants, to Enhance Drug Permeation Using Metformin Solid Dispersions, a BCS Class 3 Drug, for Oral Delivery

This research describes the relative effect of vitamin E‐based glycosides (VEGs) on the oral drug permeation and compares them with d ‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS). Metformin (MTFR) was used as a model drug. A few samples of solid dispersions (SDs) were prepared with MTFR, polyvinylpyrrolidone (PVP), and a VEG or TPGS via the solvent‐evaporation method. Drug release tests were performed. Interaction of ingredients were examined using Fourier transform infrared (FTIR) spectroscopy. Oral bioavailability of MTFR with each sample was investigated in rabbits to ascertain the relative drug permeation effect in vivo. All the samples gave more than 80% drug release in 15 min. No drug‐excipient or excipient‐excipient covalent interaction existed in the samples. As compared with plain MTFR, all MTFR‐loaded SDs enhanced oral bioavailability or in vivo permeation of MTFR in order of: VEG‐2 ≥ VEG‐1 ≥ VEG‐4 ≥ VEG‐3 ≥ TPGS. All the VEGs exerted a better drug permeation‐enhancing effect than did TPGS. In particular, the bioavailability of MTFR with VEG‐2 was ~6‐fold as compared with plain MTFR while it was ~3‐fold as compared with TPGS. VEGs are novel compounds which can be used in oral formulation as permeation enhancers for effective delivery of BCS Class 3 drugs.