Mewar University, Chittorgarh-312901, Rajasthan, India.
Department of Pharmaceutics, TRR College of Pharmacy, Hyderabad-500097, Telangana, India.
Pharm Nanotechnol. 2021;9(1):61-69. doi: 10.2174/2211738508666200708150151.
Ticagrelor (TGR), being an antiplatelet agent, belongs to BCS class IV drug with low solubility and permeability that undergoes first-pass metabolism, leading to reduced bioavailability of 36%.
The main objective of this study is to develop TGR SNEDDS for enhancing solubility and oral bioavailability.
An oil, surfactant and co-surfactant (miglyol 810, brij 35 and lauro glycol FCC) are chosen based on the maximum solubility of TGR. The selected vehicles are mixed in different ratios and are agitated mildly. Transmittance values that are more than 80 were noted and are used for constructing pseudo ternary phase diagram. Formulations that passed stability testing were evaluated for % transmission, drug content and in vitro drug release analysis. In vivo bioavailability studies of optimized SNEDDS are performed in Wistar rats.
From evaluation studies of TGR, formulation F13 with maximum drug release of 98.99% in 60 minutes, that is higher than 31.99% of the pure drug is considered as an optimised formulation. The particle size, Z average and zeta potential of the optimized TGR formulation F13 was 289.6 nm, 185.1 nm and -18.3 mV respectively. The FTIR and SEM studies do not indicate any drug excipient interaction and confirm nano size which is stable for 3 months. From in vivo bioavailability studies in rats, the C of optimized TGR SNEDDS (302.43±4.78 ng/ml) is higher than pure TGR suspension (47.32±2.75 ng/ml) and optimized SNEDDS exhibited 5 folds increase in oral bioavailability when compared to pure drug.
Hence the results reveal that, application of SNEDDS formulation technique for TGR Increases solubility and oral bioavailability.
替格瑞洛（TGR）作为一种抗血小板药物，属于 BCS 分类 IV 类药物，具有低溶解度和通透性，会经历首过代谢，导致生物利用度降低至 36%。
本研究的主要目的是开发 TGR SNEDDS 以提高溶解度和口服生物利用度。
根据 TGR 的最大溶解度选择油、表面活性剂和助表面活性剂（miglyol 810、brij 35 和 lauro glycol FCC）。选择的载体以不同比例混合并温和搅拌。记录透射值大于 80 的值，并用于构建伪三元相图。通过稳定性测试的制剂用于评估%透射率、药物含量和体外药物释放分析。在 Wistar 大鼠中进行优化的 SNEDDS 的体内生物利用度研究。
从 TGR 的评估研究中，制剂 F13 在 60 分钟内具有 98.99%的最大药物释放率，高于纯药物的 31.99%，被认为是优化的制剂。优化的 TGR 制剂 F13 的粒径、Z 均数和 Zeta 电位分别为 289.6nm、185.1nm 和-18.3mV。FTIR 和 SEM 研究表明没有药物赋形剂相互作用，并确认纳米尺寸稳定 3 个月。在大鼠体内生物利用度研究中，优化的 TGR SNEDDS 的 C（302.43±4.78ng/ml）高于纯 TGR 混悬液（47.32±2.75ng/ml），与纯药物相比，优化的 SNEDDS 口服生物利用度提高了 5 倍。
因此，结果表明，应用 SNEDDS 制剂技术可提高 TGR 的溶解度和口服生物利用度。
