Javed Aqib, Sarfraz Rai Muhammad, Mahmood Asif, Ahmad Zulcaif, Akram Muhammad Rouf, Ijaz Hira, Ali Shammas, Shahzadi Anam
College of Pharmacy, University of Sargodha, Sargodha, Pakistan.
Faculty of Pharmacy, University of Chakwal, Chakwal, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec 13. doi: 10.1007/s00210-024-03708-1.
This painless method allows drugs to penetrate the outer skin layer, offering several advantages over alternative administration routes, including ease of use and the ability to bypass enterohepatic circulation. Among transdermal drug delivery systems (TDDS), microneedle patches (MNPs) are emerging as an innovative approach for minimally invasive drug delivery, enhancing the skin permeation of substances ranging from macro to micro sizes. This study explores dissolvable microneedle patches (dMNPs) as a novel method to improve the systemic delivery of empagliflozin, an SGLT-2 inhibitor, commonly used to manage type 2 diabetes mellitus (T2DM). However, its oral administration poses challenges due to rapid absorption, variable bioavailability, and a moderate half-life that necessitates frequent dosing. The microneedle patches were manufactured using a mold-based solvent casting technique, utilizing a polymer-drug combination that dissolves upon skin application. The development of the dMNPs involved polyvinylpyrrolidone and polyvinyl alcohol. Characterization of the formulated dMNPs included scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), dissolution testing, tensile strength analysis, percentage elongation measurement, mechanical strength assessment, and skin irritation studies. The optimized dMNP formulation (MP6) exhibited notable characteristics such as sharp, uniform, pyramid-shaped needles, stability at elevated temperatures, crystalline structures of the drug and polymers, controlled weight loss upon heating, effective drug dissolution, optimal tensile strength, penetration depth, moisture content, elongation capability, and a favorable release rate. In vitro release demonstrated the enhanced properties of the dissolvable microneedle patches, with zero-order kinetics identified as the most suitable model for MP6 based on regression coefficient analysis. Overall, the characterization studies, in vitro skin irritation evaluation, confirmed the stability and biocompatibility of the optimized dMNPs, making them suitable for transdermal application.
这种无痛方法能使药物穿透皮肤外层,与其他给药途径相比具有多个优势,包括使用方便以及能够避开肠肝循环。在透皮给药系统(TDDS)中,微针贴片(MNP)正成为一种用于微创给药的创新方法,可增强从大分子到微小分子物质的皮肤渗透。本研究探索了可溶微针贴片(dMNP)作为一种改善恩格列净全身给药的新方法,恩格列净是一种常用于治疗2型糖尿病(T2DM)的钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂。然而,其口服给药存在挑战,原因在于吸收迅速、生物利用度可变以及半衰期适中,需要频繁给药。微针贴片采用基于模具的溶剂浇铸技术制造,使用了在皮肤应用时会溶解的聚合物-药物组合。dMNP的研发涉及聚乙烯吡咯烷酮和聚乙烯醇。对所制备的dMNP的表征包括扫描电子显微镜(SEM)、傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)、热重分析(TGA)、粉末X射线衍射(PXRD)、溶出度测试、拉伸强度分析、伸长率测量、机械强度评估以及皮肤刺激性研究。优化后的dMNP制剂(MP6)展现出显著特性,如尖锐、均匀的金字塔形针,在高温下的稳定性,药物和聚合物的晶体结构,加热时的可控失重,有效的药物溶解,最佳拉伸强度、穿透深度、水分含量、伸长能力以及良好的释放速率。体外释放证明了可溶微针贴片的增强性能,基于回归系数分析确定零级动力学是MP6最合适的模型。总体而言,表征研究以及体外皮肤刺激性评估证实了优化后的dMNP的稳定性和生物相容性,使其适用于透皮应用。