Efficient incorporation and protection of lansoprazole in cyclodextrin metal-organic frameworks

Int J Pharm. 2020 Jul 30:585:119442. doi: 10.1016/j.ijpharm.2020.119442. Epub 2020 May 21.

Abstract

Lansoprazole (LPZ) is an acid pump inhibitor, which readily degrades upon acidic or basic conditions and under heating. We investigated here LPZ stability upon incorporation in particles made of cyclodextrin metal-organic frameworks (CD-MOFs). LPZ loaded CD-MOFs were successfully synthesized, reaching high LPZ payloads of 23.2 ± 2.1 wt%, which correspond to a molar ratio of 1:1 between LPZ and γ-CD. The homogeneity of LPZ loaded CD-MOFs in terms of component distribution was confirmed by elemental mapping by STEM-EDX. Both CTAB, the surfactant used in the CD-MOFs synthesis, and LPZ compete for their inclusion in the CD cavities. CTAB allowed obtaining regular cubic particles of around 5 µm with 15 wt% residual CTAB amounts. When LPZ was incorporated, the residual CTAB amount was less than 0.1 wt%, suggesting a higher affinity of LPZ for the CDs than CTAB. These findings were confirmed by molecular simulations. Vibrational circular dichroism studies confirmed the LPZ incorporation inside the CDs. Solid-state NMR showed that LPZ was located in the CDs and that it remained intact even after three years storage. Remarkably, the CD-MOFs matrix protected the drug upon thermal decomposition. This study highlights the interest of CD-MOFs for the incorporation and protection of LPZ.

Keywords: Cyclodextrin; Drug stability; Inclusion complex; Lansoprazole; Metal-organic frameworks.

MeSH terms

  • Cetrimonium / chemistry
  • Cyclodextrins / chemistry*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Stability
  • Lansoprazole / administration & dosage*
  • Metal-Organic Frameworks / chemistry*
  • Microscopy, Electron, Transmission
  • Particle Size
  • X-Ray Diffraction
  • gamma-Cyclodextrins / chemistry

Substances

  • Cyclodextrins
  • Drug Carriers
  • Metal-Organic Frameworks
  • gamma-Cyclodextrins
  • Lansoprazole
  • Cetrimonium