Hydrocortisone/cyclodextrin complex electrospun nanofibers for a fast-dissolving oral drug delivery system

Abstract

The electrospinning of hydrocortisone/cyclodextrin complex nanofibers was performed in order to develop a fast-dissolving oral drug delivery system. Hydrocortisone is a water-insoluble hydrophobic drug, yet, the water solubility of hydrocortisone was significantly enhanced by inclusion complexation with hydroxypropyl-beta-cyclodextrin (HP-β-CyD). In this study, hydrocortisone/HP-β-CyD complexes were prepared in aqueous solutions having molar ratios of 1/1, 1/1.5 and 1/2 (hydrocortisone/HP-β-CyD). Highly concentrated aqueous solutions of HP-β-CyD (180%, w/v) were used for hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) in order to perform electrospinning without the use of an additional polymer matrix. The turbidity of hydrocortisone/HP-β-CyD (1/1 and 1/1.5) aqueous solutions indicated the presence of some uncomplexed crystals of hydrocortisone whereas the aqueous solution of hydrocortisone/HP-β-CyD (1/2) was homogeneous indicating that hydrocortisone becomes totally water-soluble by inclusion complexation with HP-β-CyD. Nonetheless, the electrospinning of hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) successfully yielded defect-free uniform nanofibrous structures. Moreover, the electrospinning process was quite efficient that hydrocortisone was completely preserved without any loss yielding hydrocortisone/HP-β-CyD nanofibers having the initial molar ratios (1/1, 1/1.5 and 1/2). The structural and thermal characterization of the hydrocortisone/HP-β-CyD nanofibers revealed that hydrocortisone was totally inclusion complexed with HP-β-CyD and was in the amorphous state in hydrocortisone/HP-β-CyD (1/2) nanofibers whereas some uncomplexed crystalline hydrocortisone was present in hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibers. Nevertheless, hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) complex aqueous systems were electrospun in the form of nanofibrous webs having a free-standing and flexible nature. The hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibrous webs have shown fast-dissolving behavior in water or when they were in contact with artificial saliva. Yet, the hydrocortisone/HP-β-CyD (1/2) nanofibrous web dissolved more quickly than the hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibrous webs due to the full inclusion complexation and the amorphous state of hydrocortisone in this sample. In short, the results suggest that polymer-free electrospun nanofibrous webs produced from hydrocortisone/HP-β-CyD could be quite applicable for fast-dissolving oral drug delivery systems.

Fig. 1. (a) Chemical structure and schematic illustration of HP-β-CyD and hydrocortisone molecules. Schematic representation of the (b) formation of the hydrocortisone/HP-β-CyD complex and (c) electrospinning of hydrocortisone/HP-β-CyD complex nanofibers and (d) the photographs of hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) solutions and the resulting electrospun nanofibrous webs.

Fig. 2. SEM images and the fiber diameter distribution graphs of (a-i and ii) HP-β-CyD nanofibers, (b-i and ii) hydrocortisone/HP-β-CyD (1/1) nanofibers, (c-i and ii) hydrocortisone/HP-β-CyD (1/1.5) nanofibers and (d-i and ii) hydrocortisone/HP-β-CyD (1/2) nanofibers.

Fig. 3. (a) The full and (b and c) expanded range FTIR spectra of the hydrocortisone powder, HP-β-CyD nanofibers (NF), hydrocortisone/HP-β-CyD (1/1, 1/5 and 1/2) nanofibers (NF) and hydrocortisone/HP-β-CyD (1/1) physical mixture (PM).

Fig. 4. XRD patterns of the hydrocortisone powder, HP-β-CyD nanofibers (NF), hydrocortisone/HP-β-CyD (1/1, 1/5 and 1/2) nanofibers (NF), hydrocortisone/HP-β-CyD (1/2) nanofibers (NF) after 3 months of storage (at 55–65% RH and ∼22 °C) and hydrocortisone/HP-β-CyD (1/1) physical mixture (PM).

Fig. 5. DSC thermograms of the hydrocortisone powder, HP-β-CyD nanofibers (NF), hydrocortisone/HP-β-CyD (1/1, 1/5 and 1/2) nanofibers (NF), and hydrocortisone/HP-β-CyD (1/1) physical mixture (PM).

Fig. 6. (a) TGA thermograms and (b) derivatives of hydrocortisone powder, HP-β-CyD nanofibers (NF) and hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibers (NF).

Fig. 7. ¹H-NMR spectra of pure hydrocortisone, HP-β-CyD nanofibers (NF), and hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibers (NF). ¹H-NMR spectra were recorded by dissolving the samples in d6-DMSO. The characteristic peaks of hydrocortisone and HP-β-CyD are highlighted with yellow and purple colors, respectively.

Fig. 8. (a) Phase solubility diagram of the hydrocortisone/HP-β-CyD complex system and the inset photograph of the hydrocortisone/HP-β-CyD systems for different HP-β-CyD concentrations. (b) Time dependent release profiles and (c) UV-vis spectra of aqueous solutions of hydrocortisone and hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibers (NF).

Fig. 9. The dissolution behaviour of hydrocortisone powder and hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibrous webs in distilled water. The pictures were captured from the video given as Video S1.

Fig. 10. The disintegration behaviour of hydrocortisone/HP-β-CyD (1/1), hydrocortisone/HP-β-CyD (1/1.5) and hydrocortisone/HP-β-CyD (1/2) nanofibrous webs in an artificial saliva environment. The pictures were captured from the video given as Video S2.