Monika Bhairam, Ravindra Kumar Pandey, Shiv Shankar Shukla, Bina Gidwani
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引用次数: 0
摘要
目的 在本研究中，采用实验设计（DoE）方法开发并优化了存在溶解性问题的抗病毒药物多鲁曲韦的纳米悬浮液。与纯药物相比，该纳米悬浮液显著提高了药物溶解度。优化后的纳米悬浮液显示出理想的药代动力学特征、表面形态和药物含量。结果多鲁曲韦纳米颗粒的平均粒径为 337.1 nm，多分散指数较低，ZETA电位为负，这表明其具有良好的稳定性。在 Wistar 大鼠身上进行的实验结果表明，与纯药相比，纳米悬浮剂的生物利用度更高，AUC 值也有所提高。优化配方改善了体外药物释放，提高了溶解度，并具有良好的稳定性。超声时间在控制纳米颗粒大小方面起着至关重要的作用。使用差示扫描量热法和 X 射线衍射法进行的进一步表征证实了纳米悬浮液中药物的无定形性质，从而解释了溶解度提高的原因。所开发的 DGSD 纳米悬浮制剂通过促进药物吸收和提高疗效，显示出有效治疗 HIV 阳性患者的潜力。这种创新方法有望克服艾滋病药物的溶解性难题，并有助于提高治疗效果。还需要进一步的研究和临床研究来验证 DGSD-纳米悬浮剂作为多鲁曲韦和其他溶解性较差药物的可行给药系统的有效性和安全性。
Preparation, Optimization, and Evaluation of Dolutegravir Nanosuspension: In Vitro and In Vivo Characterization
Purpose
In this study, a nanosuspension of dolutegravir, an antiviral drug with solubility issues, was developed and optimized using a Design of Experiments (DoE) approach. The nanosuspension showed a significant improvement in drug dissolution compared to the pure drug.
Methods
The formulation process involved high-speed homogenization and probe sonication techniques, with Soluplus as the selected surfactant. The optimized nanosuspension demonstrated desirable pharmacokinetic profiles, surface morphology, and drug content. In vitro and in vivo studies confirmed the enhanced performance of the nanosuspension.
Results
The dolutegravir nanoparticles had a mean size of 337.1 nm, a low polydispersity index, and a negative zeta potential, indicating good stability. Experimental results in Wistar rats showed higher bioavailability for the nanosuspension compared to the pure drug, as evidenced by the increased AUC value. The optimized formulation exhibited improved in vitro drug release, increased solubility, and good stability. The sonication time played a crucial role in controlling the nanoparticle size. Further characterization using differential scanning calorimetry and X-ray diffraction confirmed the amorphous nature of the drug in the nanosuspension, explaining the enhanced solubility.
Conclusion
In conclusion, the nanosuspension approach offers a promising solution for improving the bioavailability of poorly soluble drugs like dolutegravir. The developed DGSD-Nanosuspension formulation shows potential for effectively treating HIV-positive individuals by enhancing drug absorption and therapeutic efficacy. This innovative approach holds promise for overcoming solubility challenges in HIV medication and may contribute to better treatment outcomes. Further research and clinical studies are needed to validate the effectiveness and safety of DGSD-Nanosuspension as a viable delivery system for dolutegravir and other poorly soluble drugs.
期刊介绍：
The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories:
Materials science,
Product design,
Process design, optimization, automation and control,
Facilities; Information management,
Regulatory policy and strategy,
Supply chain developments ,
Education and professional development,
Journal of Pharmaceutical Innovation publishes four issues a year.
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