Mushtaq Rayan Y, Naveen Nimbagal Raghavendra, Rolla Krishna Jayanth, Al Shmrany Humood, Alshehri Sameer, Salawi Ahmad, Kurakula Mallesh, Alghamdi Majed A, Rizg Waleed Y, Bakhaidar Rana B, Abualsunun Walaa A, Hosny Khaled M, Alamoudi Abdulmohsin J
Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, Karnataka, India.
Front Pharmacol. 2024 Aug 23;15:1433734. doi: 10.3389/fphar.2024.1433734. eCollection 2024.
The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities.
The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and release patterns of the FSB formulation were evaluated. Additionally, an forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel.
The optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel.
This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The forming hydrogel further supported the formulation's applicability for injectable applications, providing rapid gelation and sustained drug release. The results corroborate the formulation's efficacy, underscoring its potential for improving the treatment of osteoarthritis.
本研究旨在运用质量源于设计（QbD）原则和实验设计（DOE）系统地优化载有氟比洛芬的双分子层脂质体（FSB）的制备工艺。目标是开发一种具有更高包封率和靶向给药能力的优化制剂。
优化过程涉及应用QbD原则和DOE以实现所需的制剂特性。加入超顺磁性氧化铁纳米颗粒（SPIONs）以赋予磁响应性。评估了FSB制剂的大小、包封率、形态和释放模式。此外，还开发了一种包含FSB的可注射水凝胶，并评估了其凝胶化时间和药物释放动力学。对骨关节炎大鼠进行了研究，以评估载有FSB的水凝胶的疗效。
优化后的FSB制剂产生的颗粒大小为453.60纳米，包封率为91.57%。SPIONs的加入增强了磁响应性。形态学评估和释放研究证实了FSB制剂的结构完整性和缓释特性。可注射水凝胶的凝胶化时间约为40±1.8秒，且药物释放动力学得到控制。研究表明，用载有FSB的水凝胶治疗的骨关节炎大鼠的关节炎症减少了27.83%，运动活性提高了85%。
这项全面的研究突出了FSB作为一种有前景的靶向给药系统用于有效治疗骨关节炎的潜力。在制剂过程中使用QbD和DOE，以及整合SPIONs，产生了一种具有更高包封率和靶向给药能力的优化FSB制剂。可注射水凝胶进一步支持了该制剂在注射应用中的适用性，提供了快速凝胶化和持续药物释放。体内结果证实了该制剂的疗效，强调了其在改善骨关节炎治疗方面的潜力。
