Preparation of posaconazole solid dispersion via hot-melt extrusion and preliminary evaluation in vitro / 中国药科大学学报

ABSTRACT

@#Hot-melt extrusion technology was used to prepare solid dispersion of posaconazole for improving its dissolution. Solubility parameter, glass transition temperature and melting method were utilized to screen polymers. Using KollidonVA64, Soluplus, Eudragit L100 and combined carrier KollidonVA64-Eudragit L100 as polymer carrier, solid dispersion was prepared by hot-melt extrusion technology and characterized by drug dissolution. The formulation and process factor affecting dissolution were studied. The state of posaconazole in solid dispersion was characterized by differential scanning calorimetry and preliminary analysis of the stability was studied by influencing factors experiments. When using KollidonVA64-Eudragit L100(2 ∶8)as the carrier, 10 % triethyl citrate as the plasticizer and extrusion temperature of 150 °C, the dissolution of posaconazole was improved significantly. Drug was molecular or amorphous form in the carrier. Proportion of Eudragit L100 and KollidonVA64, temperature, drug loading and plasticizer influenced dissolution of posaconazole. Solid dispersion was stable for high temperature and strong light but sensitive to high humidity. Solid dispersion using hot-melt extrusion technology can significantly improve the dissolution of posaconazole.