Preparation and Performance Investigation of Aprepitant Ternary Supersaturated Solid Dispersion System
OBJECTIVE To improve the solubility of the insoluble drug aprepitant,solve the problem of solubilization in acid and crystallization and precipitation in alkali of aprepitant,select polymer carriers with different functions,prepare ternary solid dispersions,and investigate their performance.METHODS Binary solid dispersions were prepared by solvent-melt method,and the solubility and dissolution rate were used as indicators to screen the solubilization-enhancing carrier materials.The crystallization inhibition performance of each polymer in different concentrations of drug solutions was investigated by the medium transfer method,and the best precipitation inhibitor was screened.The ternary solid dispersions were prepared by hot melt extrusion technique,and the ternary solid dispersion prescriptions were preferably selected with the indexes of solubility and crystal inhibition time.The presence of the drug in the carrier was confirmed by X-ray diffraction analysis,and the dynamic solubility and physical stability of the ternary solid dispersion in simulated intestinal fluid under accelerated conditions were investigated.RESULTS The binary solid dispersion prepared by hydrophilic polymer PVP K30 showed fast dissolution and good solubilization,the enterosoluble polymer HPMCAS showed superior crystal inhibition and prolonged the supersaturation point of aprepitant,and the ternary solid dispersion with a mass ratio of 1∶1∶3(APR∶PVP K30∶HPMCAS)was rapidly and completely released in acid(95％dissolution at 120 min).The ternary solid dispersions were completely released and maintained the solution in a highly supersaturated stable state at 6 h when the pH of the medium was shifted to 6.8,which significantly increased the dissolution degree and dissolution rate relative to the APR,and the drug existed in the carrier matrix in an amorphous form,while being able to maintain the amorphous state for at least three months under accelerated conditions.CONCLUSION Based on the physicochemical properties of different polymers,the ternary solid dispersion prepared in this work not only significantly improves the solubility of aprepitant by coordinating the dissolution rate and crystallization inhibition effect,but also solves the problem of aprepitant dissolution in stomach and precipitation in intestine,with good dissolution characteristics.
aprepitantternary polymersupersaturated drug delivery systemhot melt extrusion
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