為減輕鹽酸二甲雙胍對胃的刺激，實現其在腸道內的釋放，以鹽酸二甲雙胍為主藥，殼聚糖、海藻酸鈉為復合載體，篩選鹽酸二甲雙胍pH敏感性水凝膠微球的最佳處方及制備工藝，并對其pH敏感性及體外釋藥特性進行了考察。通過單因素試驗及正交試驗優化處方工藝，利用掃描電鏡進行結構表征，紫外分光光度法測定載藥量及包封率，轉籃法研究釋放度。結果表明，鹽酸二甲雙胍pH敏感性水凝膠微球的優選處方如下：殼聚糖與海藻酸鈉的總濃度為2%（質量體積比），海藻酸鈉與殼聚糖的質量比為1∶1，藥物與海藻酸鈉的質量比為2∶5，氯化鈣的交聯濃度為3.5%（質量體積比）；鹽酸二甲雙胍pH敏感性水凝膠微球在人工胃液中6 h累積釋放度小于4%，在人工腸液中6 h累積釋放度最大可達96.4%。所制備的鹽酸二甲雙胍pH敏感性水凝膠微球處方工藝穩定可靠，水凝膠微球機械強度高，生物降解性和穩定性好，是一種新型結構的鹽酸二甲雙胍給藥系統。
In order to avoid the irritation of metformin hydrochloride to the stomach and realize its release in the intestine, with metformin hydrochloride as the main drug and chitosan/sodium alginate as the composite support, the optimal formulation and preparation technology of metformin hydrochloride loaded pH-sensitive hydrogel microspheres were selected, and the pH-sensitivity and in vitro drug release characteristics were investigated. The formulation and process were optimized by single factor test and orthogonal test. The morphology was characterized by SEM. The entrapment efficiency and drug-loaded amount were determined by UV. The release degree was studied by rotating basket method. The results show that the optimized prescription is as following: chitosan and sodium alginate with a total concentration of 2%(mass-volume ratio), mass ratio of sodium alginate to chitosan =1∶1, mass ratio of drug to sodium alginate=2∶5, and 3.5% CaCl2(mass-volume ratio). The cumulative release rate is less than 4% in artificial gastric juice within 6 h, and up to 96.4% in artificial intestinal juice within 6 h. The formulation and process are stable and reliable, and the hydrogel microspheres have high mechanical strength, good biodegradability and stability. So it is a new metformin hydrochloride delivery system.
國家自然科學基金(81872770，51205204); 河北省高等學?？茖W技術研究重點項目（ZD2017032）; 河北省大學生創新創業訓練計劃項目(201810082027)