Crystal growth formation in melt extrudates

Abstract

The purpose of the study was to investigate the physical state of hot-melt extruded guaifenesin tablets containing either Acryl-EZE ® or Eudragit L100-55 ® and to study the physicochemical factors influencing crystal growth of guaifenesin on the surface of the extrudates. The powder mixtures containing Acryl-EZE ® were extruded on a single-screw Randcastle Microtruder at 20 rpm and at temperatures of 90, 95, 110 °C (zones 1, 2, 3, respectively) and 115 °C (die), before being manually cut into tablets (250 ± 5 mg). Extrudates containing Eudragit L100-55 ®, TEC and guaifenesin were extruded at temperatures ranging from 60 to 115 °C. Modulated differential calorimetry (DSC) was used to demonstrate the plasticizing effect of guaifenesin on Eudragit L100-55 ®. Powder X-ray diffraction (PXRD) showed that while the drug powder is crystalline, extrudates containing up to 25% drug exhibited an amorphous diffraction profile. Extrudates containing higher drug concentrations showed an amorphous profile with some crystalline peaks corresponding to guaifenesin, indicating that the limit of solubility of drug in the matrix had been exceeded. Scanning electron microscopy was used to demonstrate that drug crystallization was a surface phenomenon and dependent on the drug concentration. In vitro dissolution testing showed no effect of surface crystallization of guaifenesin on drug release rates of extruded matrix tablets. The influence of hydrophilic polymeric additives including PVP K25, polycarbophil, PEG 3350, poloxamer 188 or poly(ethylene oxide) as crystal growth inhibitors was investigated at a level of 10% based on the drug content. The extent of crystal growth was reduced for all additives. Complete drug release in pH 6.8 phosphate buffer was prolonged from 4 h in extrudates containing Acryl-EZE ® and guaifenesin to 8 h in extrudates containing Eudragit L100-55 ®, TEC and guaifenesin. Drug release in extrudates containing Eudragit L100-55 ® and guaifenesin was not affected by the presence of hydrophilic additives present at 10% based on the drug content. In vitro drug release studies showed no significant change during storage for up to 6 months at 25 °C/60% relative humidity and 40 °C/75% relative humidity.