Phechkrajang Chutima, Phiphitphibunsuk Wichuda, Sukthongchaikool Rapee, Nuchtavorn Nantana, Leanpolchareanchai Jiraporn
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand.
Pharmaceutics. 2023 Jun 1;15(6):1637. doi: 10.3390/pharmaceutics15061637.
The antifungal drug miconazole nitrate has a low solubility in water, leading to reduced therapeutic efficacy. To address this limitation, miconazole-loaded microemulsions were developed and assessed for topical skin delivery, prepared through spontaneous emulsification with oleic acid and water. The surfactant phase included a mixture of polyoxyethylene sorbitan monooleate (PSM) and various cosurfactants (ethanol, 2-(2-ethoxyethoxy) ethanol, or 2-propanol). The optimal miconazole-loaded microemulsion containing PSM and ethanol at a ratio of 1:1 showed a mean cumulative drug permeation of 87.6 ± 5.8 μg/cm across pig skin. The formulation exhibited higher cumulative permeation, permeation flux, and drug deposition than conventional cream and significantly increased the in vitro inhibition of compared with cream ( < 0.05). Over the course of a 3-month study conducted at a temperature of 30 ± 2 °C, the microemulsion exhibited favorable physicochemical stability. This outcome signifies its potential suitability as a carrier for effectively administering miconazole through topical administration. Additionally, a non-destructive technique employing near-infrared spectroscopy coupled with a partial least-squares regression (PLSR) model was developed to quantitatively analyze microemulsions containing miconazole nitrate. This approach eliminates the need for sample preparation. The optimal PLSR model was derived by utilizing orthogonal signal correction pretreated data with one latent factor. This model exhibited a remarkable R value of 0.9919 and a root mean square error of calibration of 0.0488. Consequently, this methodology holds potential for effectively monitoring the quantity of miconazole nitrate in various formulations, including both conventional and innovative ones.
抗真菌药物硝酸咪康唑在水中溶解度低，导致治疗效果降低。为解决这一局限性，开发了载咪康唑微乳剂并评估其用于局部皮肤给药，通过与油酸和水自发乳化制备。表面活性剂相包括聚氧乙烯山梨醇单油酸酯（PSM）和各种助表面活性剂（乙醇、2-(2-乙氧基乙氧基)乙醇或2-丙醇）的混合物。含PSM和乙醇比例为1:1的最佳载咪康唑微乳剂在猪皮上的平均累积药物渗透量为87.6±5.8μg/cm。该制剂比传统乳膏表现出更高的累积渗透率、渗透通量和药物沉积，与乳膏相比，体外抑菌作用显著增强（P<0.05）。在30±2℃温度下进行的为期3个月的研究过程中，微乳剂表现出良好的物理化学稳定性。这一结果表明其作为通过局部给药有效施用咪康唑的载体具有潜在适用性。此外，开发了一种采用近红外光谱结合偏最小二乘回归（PLSR）模型的无损技术，用于定量分析含硝酸咪康唑的微乳剂。这种方法无需样品制备。通过利用具有一个潜在因子的正交信号校正预处理数据得出最佳PLSR模型。该模型的R值为0.9919，校准均方根误差为0.0488。因此，该方法有潜力有效监测各种制剂（包括传统制剂和创新制剂）中硝酸咪康唑的含量。
