Abstract：
Lacidipine (LCD) is a potent antihypertensive agent. Fatty-based nanovesicles (FNVs) were designed to improve LCD low solubility and bioavailability. LCD-FNVs were formulated according to different proportions of cetyl alcohol, cremophor®RH40, and oleic acid adopting Box-Behnken Design. The optimized LCD-FNVs, composed of cetyl alcohol 48.4 mg, cremophor®RH40 120 mg, and oleic acid 40 mg, showed minimum vesicle size (124.8 nm), maximum entrapment efficiency % (91.04 %) and zeta potential (-36.3 mV). The optimized FNVs were then used to formulate the lyophilized orally fast-disintegrating sponge (LY-OFDS). The LY-OFDS had a very short disintegration time (58 sec), remarkably high % drug release (100 % after 15 mins), and increased the drug transbuccal permeation by over 9.5-fold compared to the drug suspension. In-vivo evaluation of antihypertensive activity in rats showed that the LY-OFDS reduced blood pressure immediately after 5 min and reached normal blood pressure 4.5-fold faster than the marketed oral tablets. In the In-vivo pharmacokinetic study in rabbits, the LY-OFDS showed 4.7-fold higher bioavailability compared with the marketed oral tablet. In conclusion, the LY-OFDS loaded with LCD-FNVs is a safe, and non-invasive approach that can deliver LCD effectively to the blood circulation via the buccal mucosa giving superior immediate capabilities of lowering high blood pressure and increasing the drug bioavailability.
摘要：
拉西地平（LCD）是一种有效的抗高血压药。设计基于脂肪的纳米囊泡(FNVs)以改善LCD低溶解度和生物利用度。根据鲸蜡醇的不同比例配制LCD-FNVs，cremophor®RH40和采用Box-Behnken设计的油酸。优化的LCD-FNVs,由鲸蜡醇48.4毫克组成，cremophor®RH40120毫克，油酸40毫克,显示最小囊泡尺寸（124.8nm），最大包封效率%(91.04%)和ζ电位(-36.3mV)。然后将优化的FNVs用于配制冻干的口服快速崩解海绵(LY-OFS)。LY-ODS的崩解时间非常短(58秒)，非常高的药物释放百分比（15分钟后为100％），与药物悬浮液相比，药物经颊渗透增加了9.5倍以上。对大鼠降压活性的体内评估表明，LY-OFS在5分钟后立即降低血压，并比市售口服片剂快4.5倍达到正常血压。在兔体内药代动力学研究中，与市售口服片剂相比,LY-OFS的生物利用度提高4.7倍.总之,装载有LCD-FNVs的LY-ODS是安全的，和非侵入性方法，可以通过颊粘膜有效地将LCD递送到血液循环，从而提供降低高血压和增加药物生物利用度的优异的即时能力。
