高水溶性药物凝胶骨架片的机械力敏感性研究  

Study on Mechanical Stress Sensitivity of Highly Water-soluble Drug Hydrogel Matrix Tablets

作　　者：冯嘉齐 范雯榕 侯琳 奚泉[1] FENG Jiaqi;FAN Wenrong;HOU Lin;XI Quan(Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]中国医药工业研究总院上海医药工业研究院,上海201203

出　　处：《中国医药工业杂志》2024年第7期948-955,964,共9页Chinese Journal of Pharmaceuticals

摘　　要：胃肠道内的机械力变化会造成高水溶性药物凝胶骨架片的释药行为变异,从而产生释药不均甚至剂量倾泻的风险。降低制剂对机械力变化的敏感性有助于药物的稳定释放。该研究选取双丙戊酸钠为模型、HPMC为骨架材料,制备了骨架片。通过溶蚀和膨胀速率测定、流变学特性评价探究了决定骨架片机械力敏感性的关键指标。并且,通过测定不同处方在高、低转速(200和100 r/min)条件下释放曲线的相似程度,考察处方与工艺中各因素对机械力敏感性的影响。结果表明,机械力敏感性取决于凝胶强度和凝胶膨胀体积2个关键指标。凝胶强度大、膨胀体积小的片剂,对机械力的敏感性低。骨架材料的重均分子量对上述2个关键指标的作用是相反的,影响结果需要综合判断。具有相近黏度的混合/单一骨架材料制成的片剂释放行为相似,但单一骨架材料片剂由于拥有较小的膨胀体积,因此对机械力的敏感性更低。当达到渗透阈值以上时,骨架材料用量将不会影响片剂的机械力敏感性。硬度只影响片剂的初始体积,并不是机械力敏感性的重要影响因素。该研究对机械力敏感性关键指标的筛选及对各影响因素的考察,可为平衡骨架片的药物释放速度和机械力敏感性提供参考。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 rheological 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 matri

关 键 词：高水溶性药物 凝胶骨架片 机械力敏感性 凝胶强度 流变学特性 溶蚀 膨胀 

分 类 号：R944.4[医药卫生—药剂学] TQ314.2[医药卫生—药学]