Shewale Harshada, Kanugo Abhishek
SVKM NMIMS School of Pharmacy and Technology Management Shirpur, Dhule, Maharashtra, India-425405; 2SVKM Institute of Pharmacy, Dhule-424001.
Department of Pharmaceutical Quality Assurance, SVKM Institute of Pharmacy, Dhule, India-424001.
Recent Pat Nanotechnol. 2024 Oct 1. doi: 10.2174/0118722105302631240816115638.
Ambrisentan is a new endothelin receptor antagonist extensively used to manage pulmonary or pulmonary arterial hypertension.
The therapeutic efficacy of Ambrisentan is limited due to its reduced solubility, higher log P (3.4), and thus less bioavailability. The recent investigation was concentrated on the improvement of solubility, and bioavailability of Ambrisentan for the therapy of hypertension via solid lipid nanoparticles (SLN) administered orally.
XRD evaluated the compatibility of Ambrisentan with lipids with FTIR, DSC, and crystalline nature. The SLN was developed by High-pressure homogenization method. The Glyceryl monostearate and Tween 80 indicated the highest solubility, hence selected. The optimization was performed with Box-Behnken Design considering the concentration of GMS (X1), Tween 80 (X2), stirring speed (X3) as independent factors and particle size (Y1), entrapment efficiency (Y2) as dependent factors. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1 and U.S. Patent 2022/0151945A1.
The optimized batch F1 showed particle size (130 nm), ZP (-18.9 mV), and entrapment efficiency (85.73 %). The dual release pattern (prompt and sustained) was achieved with the SLNloaded Ambrisentan for about 24 hours. The lyophilized sample was subjected to SEM, which also revealed a spherical shape of a colloidal dispersion with a particle size of 126 nm. Hence, the F1 batch is highly recommended for solid oral delivery and also for the pilot-plant scale-up.
A marked improvement in the solubility and dissolution of Ambrisentan was attained with the SLN. Moreover, the sustained delivery via the oral route enabled the patient's comfort, compliance, and therapeutic efficacy.
安立生坦是一种新型内皮素受体拮抗剂，广泛用于治疗肺动脉高压或肺动脉高血压。
安立生坦的治疗效果有限，因为其溶解度降低，log P值较高（3.4），因此生物利用度较低。最近的研究集中在通过口服固体脂质纳米粒（SLN）提高安立生坦的溶解度和生物利用度，以用于高血压治疗。
通过X射线衍射（XRD）、傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）和晶体性质评估安立生坦与脂质的相容性。采用高压均质法制备SLN。单硬脂酸甘油酯和吐温80的溶解度最高，因此被选用。以单硬脂酸甘油酯（GMS）浓度（X1）、吐温80（X2）浓度、搅拌速度（X3）为自变量，粒径（Y1）、包封率（Y2）为因变量，采用Box-Behnken设计进行优化。关于SLN的专利有印度专利202321053691、美国专利10973798B2、美国专利10251960B2、美国专利2021/0069121A1和美国专利2022/0151945A1。
优化后的F1批次粒径为130 nm，zeta电位（ZP）为-18.9 mV，包封率为85.73%。载有安立生坦的SLN实现了双释放模式（快速释放和持续释放），持续约24小时。对冻干样品进行扫描电子显微镜（SEM）分析，结果显示胶体分散体呈球形，粒径为126 nm。因此，强烈推荐F1批次用于固体口服给药以及中试放大生产。
SLN显著提高了安立生坦的溶解度和溶出度。此外，通过口服途径的持续给药提高了患者的舒适度、顺应性和治疗效果。
