Department of Pharmaceutics, Shadan Women's College of Pharmacy, Hyderabad, Telangana, India.
Department of Pharmaceutics, Mallareddy Pharmacy College, Secunderabad, Telangana, India.
Pharm Nanotechnol. 2020;8(6):471-484. doi: 10.2174/2211738508666201016151406.
Sorafenib tosylate (SFN) belongs to the BCS class II drug with low solubility and undergoes first-pass metabolism, which leads to reduced bioavailability of 38%.
The present study aimed at developing SFN SNEDDS to improve their solubility and bioavailability.
Preliminary solubility studies were performed to identify oil, surfactant, and co-surfactant ratios. Pseudo tertiary phase diagram was constructed to select the areas of nanoemulsion based on the monophasic region. A total of 15 formulations of SFN SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. These SNEDDS further characterized for % transmission, content of the drug, and in vitro dissolution analysis. The optimized formulation was analyzed for particle size, Z average, entrapment efficiency, and SEM analysis.
Based on the pseudo tertiary phase diagram, acrysol EL 135, kolliphor, and transcutol-P as oil, surfactant, and co-surfactant were selected, respectively. All the formulations were stable with no phase separation and maximum % transmittance of 98.92%. The formulation F15 was selected as an optimized one, based on maximum drug content of 99.89%, with 98.94% drug release within 1 hour and it will be stable for 6 months. From in vivo bioavailability studies, the Cmax of optimized SNEDDS (94.12±2.12ng/ml) is higher than pure SFN suspension (15.32±1.46 ng/ml) and the AUC0-∞ of optimized SNEDDS is also increased by 5 times (512.1±8.54 ng.h/ml) than pure drug (98.75±6.45ng.h/ml), which indicates improved bioavailability of the formulation.
SFN loaded SNEDDS could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first-pass metabolism and increased solubility. Lay Summary: Renal cell carcinoma accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States. Sorafenib is a protein kinase inhibitor indicated as a treatment for advanced renal cell carcinoma. The present study aimed at developing Sorafenib SNEDDS to improve their solubility and bioavailability. A total of 15 formulations of Sorafenib SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. Sorafenib loaded SNEDDS could potentially be exploited as a delivery system for increased oral bioavailability by 5 times when comparing with pure drug by minimizing first-pass metabolism and increased solubility.
甲苯磺酸索拉非尼（SFN）属于 BCS 类 II 药物，溶解度低，首过代谢，生物利用度降低 38%。
本研究旨在开发 SFN SNEDDS 以提高其溶解度和生物利用度。
进行初步溶解度研究以确定油、表面活性剂和共表面活性剂的比例。根据单相区域构建伪三元相图，选择基于纳米乳液的区域。制备并筛选了 15 种 SFN SNEDDS 制剂，以进行相分离和温度变化的热力学稳定性研究。这些 SNEDDS 进一步用于 %传输、药物含量和体外溶解分析。对优化配方进行粒径、Z 平均、包封效率和 SEM 分析。
根据伪三元相图，选择 acrysol EL 135、 kolliphor 和 transcutol-P 作为油、表面活性剂和共表面活性剂。所有配方均稳定，无相分离，最大透光率为 98.92%。基于最大药物含量 99.89%，选择配方 F15 作为优化配方，具有 98.94%的药物在 1 小时内释放，且在 6 个月内稳定。从体内生物利用度研究来看，优化 SNEDDS 的 Cmax（94.12±2.12ng/ml）高于纯 SFN 混悬液（15.32±1.46ng/ml），优化 SNEDDS 的 AUC0-∞也增加了 5 倍（512.1±8.54ng.h/ml）比纯药物（98.75±6.45ng.h/ml），这表明该制剂的生物利用度得到了提高。
SFN 负载的 SNEDDS 可通过最小化首过代谢和增加溶解度来提高口服生物利用度，有望作为一种药物传递系统。
