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.

Lipid-based solubilization technology via hot melt extrusion: promises and challenges.

INTRODUCTION: Self-emulsifying drug delivery systems (SEDDS) are a promising strategy to improve the oral bioavailability of poorly water-soluble drugs (PWSD). However, poor drug loading capacity and formulation instability are the main setbacks of traditional SEDDS. The use of polymeric precipitation inhibitors was shown to create supersaturable SEDDS with increased drug loads, and their solidification can help to overcome the instability challenge. As an alternative to several existing SEDDS solidification technologies, hot melt extrusion (HME) has the potential for lean and continuous manufacturing of supersaturable solid-SEDDS. Despite being ubiquitously applied in solid lipid and polymeric processing, HME has not yet been widely considered for the preparation of SEDDS. AREAS COVERED: The review begins why SEDDS as the preferred lipid-based delivery systems (LBDS) is suitable for the oral delivery of PWSD and discusses the common barriers to oral administration. The potential of LBDS to surmount them is discussed. SEDDS as the flagship of LBDS for PWSD is proposed with a special emphasis on solid-SEDDS. Finally, the opportunities and challenges of HME from the lipid-based excipient (LBE) processing and product performance standpoint are highlighted. EXPERT OPINION: HME is a continuous, solvent-free, cost-effective, and scalable technology for manufacturing solid supersaturable SEDDS. Several critical formulations and process parameters for successfully preparing SEDDS via HME are identified.

Lipidic dispersion to reduce food dependent oral bioavailability of fenofibrate: In vitro, in vivo and in silico assessments.

Novel formulations that overcome the solubility limitations of poorly water soluble drugs (PWSD) are becoming ever more critical to a drug development process inundated with these compounds. There is a clear need for developing bio-enabling formulation approaches to improve oral bioavailability for PWSD, but also to establish a range of predictive in vitro and in silico biopharmaceutics based tools for guiding formulation design and forecasting in vivo effects. The dual aim of this study was to examine the potential for a novel lipid based formulation, termed a lipidic dispersion, to enhance fasted state oral bioavailability of fenofibrate, while also assessing the predictive ability of biorelevant in vitro and in silico testing. Formulation as a lipidic dispersion improved both dissolution and solubilisation of fenofibrate through a combination of altered solid state characteristics and incorporation of solubilising lipidic excipients. These changes resulted in an increased rate of absorption and increased maximal plasma concentrations compared to a commercial, micronised product (Lipantil® Micro) in a pig model. Combination of biorelevant in vitro measurements with in silico physiologically based pharmacokinetic (PBPK) modelling resulted in an accurate prediction of formulation performance and forecasts a reduction in food effects on fenofibrate bioavailability through maximising its fasted state dissolution.