Hussain Afzal, Khan Tasneem, Siddique Mohd Usman Mohd, Altamimi Mohammad A, Ramzan Mohhammad
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Int J Pharm X. 2025 Aug 18;10:100378. doi: 10.1016/j.ijpx.2025.100378. eCollection 2025 Dec.
The study explored HSPiP and QbD-(quality by design) enabled optimized cubosomes for sustained drug release, improved permeation, and enhanced oral bioavailability. OCUB1 (the optimized product) was characterized for size, zeta potential (ZP), thermal analysis, and surface roughness. drug release and hemolysis studies were carried out using a dialysis membrane and rat erythrocytes (4 % suspension), respectively. An non-everted intestinal permeation study (180 min) compared permeation potential between DS (suspension) and OCUB1. pharmacokinetic (PK) study investigated PK parameters in rats whereas hematological and biochemical assays ensured the safety of OCUB1. HSPiP predicted glyceryl monooleate (GMO), poloxamer-188, and polyvinyl alcohol (PVA) as optimal excipients based on minimum RED (relative energy difference) values while QbD identified OCUB1 as the most optimized formulation with desirable attributes such as low size (169 nm), high ZP (-29.2 mV), low polydispersity index (0.23), and maximum entrapment efficiency (85.3 %). Thermal analysis confirmed solubilization of TOTA in OCUB1, and atomic force microscopy (AFM) technique confirmed its cubical shape. OCUB1 showed extended drug release (98.1 % over 48 h) and sustained permeation ( = 6.69 μg/cm/min, steady state flux) across rat intestine as compared to DS ( = 9.172 μg/cm/min). PK parameters exhibited significant improvement, with 3.2-fold increase in C as compared to the DS. hemolysis, along with biochemical and hematological assays, ensured the safety of OCUB1 for oral delivery. Conclusively, OCUB1 presents a promised alternative to conventional capsule, offering reduced side effects and enhanced patient compliance.
该研究探索了热休克蛋白诱导伴侣蛋白（HSPiP）和质量源于设计（QbD）技术，以实现用于药物持续释放、改善渗透及提高口服生物利用度的优化立方液晶纳米粒。对OCUB1（优化产品）进行了粒径、zeta电位（ZP）、热分析和表面粗糙度表征。分别使用透析膜和大鼠红细胞（4%悬浮液）进行药物释放和溶血研究。一项非外翻肠渗透研究（180分钟）比较了DS（悬浮液）和OCUB1之间的渗透潜力。药代动力学（PK）研究考察了大鼠体内的PK参数，而血液学和生化分析确保了OCUB1的安全性。基于最低相对能量差（RED）值，HSPiP预测单油酸甘油酯（GMO）、泊洛沙姆-188和聚乙烯醇（PVA）为最佳辅料，而QbD确定OCUB1为最优化制剂，具有低粒径（169nm）、高ZP（-29.2mV）、低多分散指数（0.23）和最大包封率（85.3%）等理想特性。热分析证实了总睾酮（TOTA）在OCUB1中的溶解，原子力显微镜（AFM）技术证实了其立方形状。与DS相比，OCUB1在大鼠肠道中显示出延长的药物释放（48小时内释放98.1%）和持续渗透（稳态通量J = 6.69μg/cm/min）。PK参数有显著改善，与DS相比，Cmax增加了3.2倍。溶血以及生化和血液学分析确保了OCUB1口服给药的安全性。总之，OCUB1是传统胶囊的一个有前景的替代品，具有减少副作用和提高患者依从性的优点。
