Metronidazole/Hydroxypropyl-β-Cyclodextrin inclusion complex nanofibrous webs as fast-dissolving oral drug delivery system.

Abstract

In this study, Metronidazole/Hydroxypropyl-β-Cyclodextrin (HP-β-CyD) inclusion complex nanofibrous webs were produced via electrospinning for the purpose of fast-dissolving oral drug delivery. The Metronidazole/HP-β-CyD inclusion complex aqueous solutions having two different molar ratio of Metronidazole/HP-β-CyD (1/1 and 1/2) were prepared by using very high concentration of HP-β-CyD (200%, w/v) in order to achieve polymer-free electrospinning of Metronidazole/HP-β-CyD nanofibers (NF). Metronidazole was totally encapsulated and preserved without any loss during the electrospinning process in which both systems yielded Metronidazole/HP-β-CyD NF having the same initial molar ratio of 1/1 and 1/2. The electrospinning of both Metronidazole/HP-β-CyD (1/1 and 1/2) aqueous solutions yielded uniform and bead-less fiber morphology having ~190 nm average fiber diameter. Both Metronidazole/HP-β-CyD NF (1/1 and 1/2) samples were in the form of nanofibrous webs with free-standing and flexible character. The structural and thermal characterizations of Metronidazole/HP-β-CyD NF (1/1 and 1/2) proved that Metronidazole was in the inclusion complex state with HP-β-CyD in these nanofibrous webs. Metronidazole is an antibiotic which is poorly water-soluble drug, but the phase solubility and dissolution tests revealed that the water-solubility of Metronidazole was significantly enhanced by HP-β-CyD inclusion complexation. In addition, Metronidazole/HP-β-CyD (1/1 and 1/2) nanofibrous webs have shown very fast-dissolving behavior when placed in water or contacted to artificial saliva suggesting that such Metronidazole/HP-β-CyD nanofibrous webs can be suitable for fast-dissolving oral drug delivery.