Hot melt extrudates with combinations of Soluplus® and Aqoat® AS-LF or Eudragit® E PO were investigated to improve drug release and to overcome the pH-dependent release of poorly water-soluble basic (itraconazole, ITZ) and acidic (mefenamic acid, MFA) drugs. The release of ITZ was improved in both 0.1 N HCl and PBS pH 6.8 by hot-melt extrusion with combinations of Soluplus®:Aqoat® AS-LF and can be adjusted by varying the ratio of the polymers. At the ratio Soluplus®:Aqoat® AS®LF 75:25, an almost pH-independent release was achieved without any drop in the drug concentration within 24 h. A pH-independent and extended release (over 24 h) was obtained from milled extrudates when formulated in erodible matrix tablets using 15 % Methocel® K15M as the carrier. The release of MFA from extrudates with Soluplus® was immediate only in PBS pH 6.8. From extrudates with cationic Eudragit® E PO the release of MFA was slow in 0.1 N HCl and PBS pH 6.8, due to poor drug solubility and insoluble Eudragit® EPO, respectively. However, in the medium with an intermediate pH of 5.5, both MFA and Eudragit® E PO are highly ionized, and the release was fast, complete, and stable within 24 h. These release behaviors could be to some degree applicable for immediate or enteric, but not for extended-release formulations.
