Lowering melt extrusion temperature and increasing solubility and dissolution rate of telmisartan amorphous solid...

Amorphous solid dispersion (ASD) via hot melt extrusion (HME) is a solvent-free process to enhance solubility and dissolution rate of poorly water-soluble drugs. However, HME is often not feasible for drugs with high melting points, especially > 200 °C, due to chemical degradation of drugs, polymers, or both at the high temperature needed. In this investigation, the ASD of telmisartan, a weakly acidic drug with a high melting point of 263 °C and the reported solubility of ∼ 0.03 to 0.28 µg/mL at pH 3-7 at 37 °C, was developed by HME using Kollidon® VA 64 as the polymeric carrier. The aqueous solubility of telmisartan increased greatly to > 300 mg/mL by acid-base supersolubilization (ABS) in the presence of the weak base, meglumine. In addition to increasing solubility in aqueous media, the acid-base interaction also occurred in the solid state, whereby the melting temperature of the telmisartan-meglumine mixture decreased to 120 °C, much below telmisartan's melting point of 263 °C. ASDs of telmisartan-meglumine-Kollidon® VA 64 ternary systems with 10 % and 20 % drug loading could be extruded at 120 °C. DSC and PXRD of extrudates confirmed complete conversion of telmisartan to the amorphous state, which dissolved much faster than crystalline telmisartan. Thus, the ABS approach provided a rapidly dissolving ASD of telmisartan that could be extruded at the relatively low temperature of 120 °C.