Preparation and Characterization of Ternary Indomethacin Solid Dispersion Based on Quality by Design (QbD) Concept / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare a ternary supersaturated indomethacin (IND) solid dispersion and investigate its characteristics by screening carrier materials with different functions based on quality by design (QbD) concept. METHODS: Based on dissolution tests, the carriers with solubilization function were selected and the appropriate drug loading ratio of binary solid dispersion was determined. The material as inhibitor of precipitation was chosen using the solvent shift method. The IND ternary supersaturated solid dispersion was prepared by the hot melt extrusion of IND, solubilization material and precipitation inhibitor. The dispersion state of IND was identified by differential scanning calorimetry and powder X-ray diffraction, and its characteristics were explored by the powder wettability test and the stability test. RESULTS: The binary IND solid dispersion with Eudragit EPO could sharply increase IND dissolution rate with a behavior of more than 80%dissolution within 5 min but subsequently followed an obvious concentration decline. Kollidon VA64 had a satisfactory effect of precipitation inhibition for IND supersaturated solution in that the concentration of 0.1% could keep the 50 μg•mL-1 IND solution unchanged within 30 min. The ternary solid dispersion with a mass ratio of 1:2:0.3 (IND:EPO:VA64) could significantly increase the dissolution of IND, eliminating the crystallization and precipitation of the drug in the supersaturated system during the dissolution process and enabling the drug to maintain amorphous form within 3 months. CONCLUSION: Based on the understanding of the functions of different carrier materials and the QbD concept, it could effectively improve the formulation design of solid dispersions. The prepared ternary IND solid dispersions have excellent drug dissolution behavior.