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。