Enhanced dissolution and stability of lansoprazole by cyclodextrin inclusion complexation: preparation, characterization, and molecular modeling

Abstract

In this study, lansoprazole (LSP)/cyclodextrin (CD) inclusion complexes were prepared using a fluid bed coating technique, with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HPCD) as the host molecules, respectively, to simultaneously improve the dissolution and stability of LSP. The dissolution rate and stability of LSP was dramatically enhanced by inclusion complexation regardless of CD type. LSP/HPCD inclusion complex was more stable under illumination than LSP/β-CD inclusion complex. Differential scanning calorimetry and powder X-ray diffractometry proved the absence of crystallinity in both LSP/CD inclusion complexes. Fourier transform infrared spectroscopy together with molecular modeling indicated that the benzimidazole of LSP was included in the cavity of both CDs, while LSP was more deeply included in HPCD than β-CD. The enhanced photostability was due to the inclusion of the sulfinyl moiety into the HPCD cavity. CD inclusion complexation could improve the dissolution and stability of LSP.

Fig. 1

Chemical structure of lansoprazole

Fig. 2

Dissolution profiles of lansoprazole (LSP), LSP/β-CD physical mixture (LSP/β-CD-PM) and inclusion complexes (LSP/β-CD-IC), LSP/HPCD physical mixture (LSP/HPCD-PM) and inclusion complexes (LSP/HPCD-IC)

Fig. 3

a DSC thermogram of lansoprazole (LSP), β-CD, LSP/β-CD physical mixture (LSP/β-CD-PM) and inclusion complexes (LSP/β-CD-IC). b DSC thermogram of lansoprazole (LSP), HPCD, LSP/HPCD physical mixture (LSP/HPCD-PM) and inclusion complexes (LSP/HPCD-IC)

Fig. 4

a Powder X-ray diffractogram of lansoprazole (LSP), β-CD, LSP/β-CD physical mixture (LSP/β-CD-PM), and inclusion complexes (LSP/β-CD-IC). b Powder X-ray diffractogram of lansoprazole (LSP), HPCD, LSP/HPCD physical mixture (LSP/HPCD-PM), and inclusion complexes (LSP/HPCD-IC)

Fig. 5

a FTIR spectrogram of lansoprazole (LSP), β-CD, LSP/β-CD physical mixture (LSP/β-CD-PM), and inclusion complexes (LSP/β-CD-IC). b FTIR spectrogram of lansoprazole (LSP), HPCD, LSP/HPCD physical mixture (LSP/HPCD-PM), and inclusion complexes (LSP/HPCD-IC)

Fig. 6

Remained LSP concentration after 5-day investigation under high temperature (40°C and 60°C), high humidity (75% and 92.5% RH), and ilumination (4,500 ± 500 lx) compared among LSP/β-CD inclusion complex, LSP/HPCD inclusion complex and free LSP (*P < 0.05, **P < 0.01)

Fig. 7

Molecular model of LSP a, β-CD b, LSP/β-CD inclusion complex c, HPCD d, and LSP/HPCD inclusion complex e