目的 研究羥丙基甲基纖維素(HPMC)親水凝膠對(duì)托拉塞米滲透的影響.方法 以HPMC為親水凝膠的輔料,托拉塞米為模型藥物,采用三室滲透裝置測定藥物透過中間室的速度,實(shí)驗(yàn)溫度為37 ℃,測定時(shí)間為1、3、7、10、24 h,考察HPMC的不同質(zhì)量濃度、黏度對(duì)藥物滲透速度的影響,與藥物本身的滲透速度比較計(jì)算阻滯率.結(jié)果 半透膜本身對(duì)藥物的平衡速度有一定影響,37 ℃下10 h透過率約50%,24 h基本達(dá)到平衡藥物.在HPMC凝膠的存在下,阻滯率隨著測定時(shí)間的延長而逐步減少,7 h后趨于平緩.HPMC的質(zhì)量濃度越大對(duì)藥物的阻滯率越大,黏度升高則阻滯率增加.合理的測定條件為HPMC K100M質(zhì)量濃度分別為5、10、20 mg/mL,托拉塞米質(zhì)量濃度為50 μg/mL,在37 ℃水浴條件下,測定時(shí)間為10 h.相同型號(hào)(100M)的進(jìn)口與國產(chǎn)HPMC在10、5 mg/mL時(shí)阻滯率基本一致,但在20 mg/mL時(shí),國產(chǎn)HPMC的阻滯率明顯大于進(jìn)口產(chǎn)品.結(jié)論 HPMC溶脹形成的凝膠層對(duì)托拉塞米的滲透具有阻滯作用,對(duì)HPMC應(yīng)用到緩釋骨架片的研究提供參考.

Objective To study the effect of hydroxypropyl methyl cellulose (HPMC) hydrogel on penetrability of torasemide. Methods HPMC was prepared into hydrophilic gel, and torasemide was used as representative drug. A device with three compartments was used to determine penetration speed of drug through the middle chamber. Penetration of drug through hydrophilic gel was tested at 1, 3, 7, 10, and 24 h under 37 ℃. The influences of concentration and viscosity of HPMC on penetration speed were taken into consideration. Block rate was calculated by the penetration speed of drug itself. Results Semipermeable membrane had influence on the balance speed of the drug. Under 37 ℃, the penetrated drug molecules was about 50% at 10 h, and the system achieves balance at 24 h. In the presence of the gel, block rate reduced gradually with the time increasing, became flat after 7 h. The higher concentrations of HPMC, the larger block rates of the drug. And the lager viscosities, the larger block rates of the drug. The reasonable standardized condition was as following: 37 ℃ water bath, the concentrations of HPMC were 5, 10, and 20 mg/mL, the concentration of torasemide was 50 μg/mL, and those were determined at 10 h. The same type (100 M) of domestic and imported HPMC was compared to find their difference. Their block rates were similar at 10 mg/mL and 5 mg/mL. But the block rate of domestic product was significantly greater than that of imported product at high concentration. Conclusion HPMC hydrogel has blocking effect on penetrability of torasemide which may provide references on sustained release matrix tablets prepared by HPMC.

天津市應(yīng)用基礎(chǔ)與前沿技術(shù)研究計(jì)劃項(xiàng)目(13JCZDJ28500)