Simultaneous taste-masking and oral bioavailability enhancement of T Ligustrazine by forming sweet salts
Simultaneous taste-masking and oral bioavailability enhancement of T Ligustrazine by forming sweet salts
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通过形成甜盐同时掩味和增强 T 川芎嗪的口服生物利用度
DOI：
10.1016/j.ijpharm.2020.119089
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发表时间：
2020
影响因子：
5.8
通讯作者：
Changquan Calvin Sun
中科院分区：
文献类型：
--
作者：
Xinghua Zhao;Qiang Li;Chenguang Wang;Shenye Hu;Xin He;Changquan Calvin Sun
川芎嗪（Tetramethylpyrazine，TMP）是一种药用活性成分，但其商业化的磷酸盐（TMP-Pho）具有苦味和口服生物利用度低的缺点。我们通过与两种甜味剂乙酰磺胺酸（Acs）和糖精（Sac）形成盐来应对这些挑战。两种盐都有效地掩盖了TMP的苦味。与TMP-Pho相比，TMP-Sac显示出低43%的溶解度和低11%的渗透性，而TMP-Acs显示出更高（两倍）的溶解度但低24%的渗透性。TMP-Acs和TMP-Sac均通过降低TMP吸收速率而表现出约40%的高生物利用度。因此，与两种甜味剂形成盐同时解决了TMP的苦味和较低生物利用度带来的挑战。
Ligustrazine (or Tetramethylpyrazine, TMP) is an active pharmaceutical ingredient that faces the challenges ofbitter taste and low oral bioavailability by the commercial phosphate salt (TMP-Pho). We tackled these challenges by forming salts with two sweeteners, acesulfame (Acs) and saccharine (Sac). Both salts effectively masked the bitter taste of TMP. Compared to TMP-Pho, TMP-Sac shows 43% lower solubility and 11% lower permeability while TMP-Acs shows higher (two-fold) solubility but 24% lower permeability. Both TMP-Acs and TMP-Sac exhibited approximately 40% higher bioavailability through reducing the rate of TMP absorption. Thus, salt formation with both sweeteners simultaneously addressed the challenges brought about by the bitter.taste and lower bioavailability of TMP.