Solid microemulsion preconcentrates on pH responsive metal-organic framework for tableting

Eur J Pharm Biopharm. 2023 May:186:105-111. doi: 10.1016/j.ejpb.2023.03.010. Epub 2023 Mar 22.

Abstract

Poorly water-soluble drugs are frequently formulated with lipid-based formulations including microemulsions and their preconcentrates. We detailed the solidification of drug-loaded microemulsion preconcentrates with the acid-sensitive metal-organic framework ZIF-8 by X-ray powder diffraction and solid-state nuclear magnetic resonance spectroscopy. Adsorption and desorption dynamics were analyzed by fluorescence measurement, high-performance liquid chromatography, dynamic light scattering and 1H-DOSY experiments using the model compounds Nile Red, Vitamin K1, and Lumefantrine. Preconcentrates and drugs were successfully loaded onto ZIF-8 while preserving its crystal structure. The solid powder was pressable to tablets or 3D-printed into oral dosage forms. At low pH, colloidal solutions readily formed, solubilizing the poorly water-soluble compounds. The use of stimuli-responsive metal organic frameworks as carriers for the oral delivery of lipid-based formulations points towards solid dosage forms readily forming colloidal microemulsions.

Keywords: Metal–organic frameworks; Microemulsion preconcentrate; Microemulsions; PWSD; SMEDDS; ZIF-8; pH responsive.

MeSH terms

  • Drug Delivery Systems
  • Emulsions / chemistry
  • Hydrogen-Ion Concentration
  • Lipids / chemistry
  • Metal-Organic Frameworks*
  • Tablets
  • Water / chemistry

Substances

  • Metal-Organic Frameworks
  • Water
  • Emulsions
  • Lipids
  • Tablets