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

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.

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Kolliphor® RH40 and polyethylene glycol 400 (PEG 400) were kindly provided by BASF SE (Ludwigshafen, Germany). Capmul® MCM and Captex® 355 were kindly provided by Abitec Corporation (Columbus, Ohio, USA). Labrafil® M 1944 CS, Maisine® and Transcutol® P were a gift from Gattefossé (Lyon, France). 2-Methylimidazole (99%), Zinc acetate dihydrate (Zn(OAc)2·2H2O, ≥98%,), Nile Red (≥97%), Vitamin K1 (≥99%), Lumefantrine (≥98%), Acetonitrile (ACN, ≥99%), Methanol (MeOH, ≥99%), Trifluoracetic acid (TFA, ≥99%), Formic acid (FA, ≥98%), and sodium chloride (NaCl, 99%) were purchased from Merck KGaA (Darmstadt, Germany). Kolliphor® EL and sesame oil purchased from VWR International GmbH (Ismaning, Germany). Tableting mixture “compaction blend for technical application” consisting of 88% (all % in w/w unless noted otherwise) lactose, 9% cellulose, 2% aluminum oxide and 1% magnesium stearate was acquired from Meggle (Wasserburg am Inn, Germany) and microcrystalline cellulose ‘‘MC-101 SP” from Lehmann & Voss (Hamburg, Germany). Bentonite was purchased from Caesar & Loretz GmbH (Hilden, Germany). Hydroxypropyl methylcellulose was acquired from JRS Pharma GmbH & Co. KG (Rosenberg, Germany). Deionized, purified water (Millipore water, hereinafter referred to as water) was generated by in-house Millipore purification system from Merck KGaA. All other standard chemicals and laboratory consumables, if not stated otherwise, were purchased from either VWR International GmbH or Merck KGaA.

Lena Scheller, Stephanie Bachmann, Theresa Zorn, Simon Hanio, Uwe Gbureck, Dimitrios Fatouros, Ann-Christin Pöppler, Lorenz Meinel, Solid microemulsion preconcentrates on pH responsive metal-organic framework for tableting, European Journal of Pharmaceutics and Biopharmaceutics, Volume 186, 2023, Pages 105-111, ISSN 0939-6411,

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