The changes of mechanical stress in the gastrointestinal tract can cause variations in the release of highly water-soluble drug hydrogel matrix tablets,resulting in the risks of uneven drug release and even dose dumping.Therefore,reducing the sensitivity of the preparations to mechanical force changes can help stabilize the release of the drug.In this study,sodium divalproate was selected as the model drug and its matrix tablets were prepared with HPMC as the matrix carrier polymers.The key indicators determining the mechanical stress sensitivity were explored through the measurement of erosion and swelling rates,and theological characteristics evaluation.The influences of various formulation and process factors on the mechanical stress sensitivity were explored by calculating the similarity of release curves at high and low rotation speeds(200 and 100 r/min).The results showed that the mechanical stress sensitivity depended on two key indicators:gel strength and gel swelling volume.The tablets with greater gel strength and smaller swelling volume had lower sensitivity to mechanical force.The weight-average molecular weight of the matrix material had opposite effects on the above two indicators,and its impact needed to be comprehensively judged.The release behaviors of the tablets prepared by the mixed matrix materials and single matrix material with similar viscosity were similar,but the tablets prepared by single matrix material had lower sensitivity to mechanical force due to their smaller swelling volume.When the permeation threshold was reached,the amount of matrix material in the formulation would not affect the sensitivity of the tablets to mechanical force.Hardness only affected the initial volume of the tablets and it was not an important factor affecting the mechanical stress sensitivity.The selection of key indicators of mechanical stress sensitivity and the investigation of various influencing factors can provide references for balancing the drug release rate and mechanical stress sensitivity of matrix tablets.
维普
万方数据
