Thota Sunil Kumar, Dudhipala Narendar, Katla Venumadhav, Veerabrahma Kishan
Department of Nanotechnology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India.
Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India.
AAPS PharmSciTech. 2023 Jan 18;24(1):38. doi: 10.1208/s12249-022-02495-3.
Efavirenz (EFV) is an anti-HIV drug with high dose and 40% oral bioavailability (BA). The aim was to improve the bioavailability by designing cationic solid SMEDDS. Solubility data, ternary phase diagrams, and central composite design were employed in design. Globule size, TEM, DSC, and SEM studies were used for characterization. Optimized L-SMEDDS contained 20 mg of EFV, 10 mg of Peceol, 43.5 mg of Tween 80, and 40 mg of Labrafac Lipophile WL-1349 and the characters included mean globule size-94 nm, PDI-0.255, and ZP-28 mV. Later, octadecylamine was added to get L-SMEDDS with + 38 mV charge. L-SMEDDS was converted into solid S-SMEDDS by adsorbing onto silica carriers. Syloid XDP was preferred based on flow and oil adsorption capacity. The % drug (EFV) release from powder, L-SMEDDS, and solid SMEDDS were 14.04, 94.47, and 85 respectively in first 30 min. TEM picture showed dispersed globules. DSC and SEM studies indicated the loss of drug crystallinity in S-SMEDDS. Pharmacokinetic (PK) studies in Wistar rats revealed 4.12 fold hike in BA for optimized cationic S-SMEDDS when compared to EFV suspension. Increased absorption could be due to the positive charge on globules. Thus, cationic S-SMEDDS emerged as a potential novel delivery system for improvement in BA and has scope for reducing the high dose for AIDS patients by future clinical studies.
依非韦伦（EFV）是一种高剂量且口服生物利用度（BA）为40%的抗HIV药物。目的是通过设计阳离子固体自微乳化药物传递系统（SMEDDS）来提高生物利用度。在设计过程中采用了溶解度数据、三元相图和中心复合设计。通过球粒大小、透射电子显微镜（TEM）、差示扫描量热法（DSC）和扫描电子显微镜（SEM）研究进行表征。优化后的液体SMEDDS含有20毫克依非韦伦、10毫克肉豆蔻酸异丙酯、43.5毫克吐温80和40毫克亲脂性Labrafac Lipophile WL - 1349，其特征包括平均球粒大小为94纳米、多分散指数（PDI）为0.255和zeta电位（ZP）为28毫伏。随后，添加十八胺以获得电荷为+38毫伏的液体SMEDDS。通过吸附到二氧化硅载体上，将液体SMEDDS转化为固体SMEDDS。基于流动性和吸油能力，优选Syloid XDP。在前30分钟内，粉末、液体SMEDDS和固体SMEDDS中药物（依非韦伦）的释放率分别为14.04%、94.47%和85%。TEM照片显示球粒分散。DSC和SEM研究表明固体SMEDDS中药物结晶度丧失。在Wistar大鼠中进行的药代动力学（PK）研究显示，与依非韦伦混悬液相比，优化后的阳离子固体SMEDDS的生物利用度提高了4.12倍。吸收增加可能是由于球粒上的正电荷。因此，阳离子固体SMEDDS作为一种潜在的新型给药系统出现，可用于提高生物利用度，并且通过未来的临床研究有降低艾滋病患者高剂量用药的空间。
