• Craig, Duncan Q. M.
• Zhao, Min
• Tuleu, Catherine
• Forbes, Claire
• Keating, Alison V.
• Soto, Jessica

Abstract

<p>Hot melt extrusion has gained considerable attention as a novel technique for taste masking of bitter APIs. The aim of this study was to investigate whether hot melt extrusion could be used to develop taste masked formulations of isoniazid and also to evaluate and correlate different taste assessment methods Two polymers with different physico-chemical properties, Soluplus and Eudragit E-PO were chosen as carriers for the drug. Eudragit E-PO has already been widely used for taste masking due to its selective release properties, while Soluplus has not been studied in this regard but provides a useful comparator of a polymer that should release the drug reasonably efficiently. Polymeric formulations of isoniazid were produced with drug loadings of 20% and 30% w/w. The solid state characteristics of the formulations were assessed by differential scanning calorimetry and powder X-ray diffraction. The taste of isoniazid was assessed using the rodent Brief Access Taste Aversion (BATA) model, while formulations were assessed using the electronic tongue and dissolution under simulated oral conditions. Investigation into the drug loading effect with these two polymers showed that all Soluplus based extrudates with drug loading up to 30% w/w were fully amorphous while Eudragit E-PO based extrudates contained crystalline drug as demonstrated by both DSC and PXRD, dependent on loading. BATA testing of isoniazid gave an IC50 value, i.e. the dose of drug which inhibits 50% of licks, of 11.1mg/mL. Taste assessment of the formulations using both simulated oral drug release and the electronic tongue demonstrated that Eudragit E-PO based formulations had a better taste masking efficiency than Soluplus. This is due to the fact that significantly less isoniazid is released from the Eudragit E-PO based formulations under oral conditions.</p>

Topics

• impedance spectroscopy
• polymer
• amorphous
• melt
• laser emission spectroscopy
• powder X-ray diffraction
• differential scanning calorimetry
• melt extrusion