Ullah Kamran Hidayat, Raza Faisal, Munawar Syed Mohsin, Sohail Muhammad, Zafar Hajra, Zafar Mazhar Iqbal, Ur-Rehman Tofeeq
Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Polymers (Basel). 2021 Sep 30;13(19):3376. doi: 10.3390/polym13193376.
The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Hydration enhancement effect was used to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% /, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.
本研究旨在开发泊洛沙姆407（P407）凝胶，用于经指甲递送具有足够凝胶强度和载药量的抗真菌疏水药物。通过使用功能性添加剂提高了P407凝胶的凝胶强度和载药量。利用水化增强效应来选择最佳的指甲渗透促进剂。采用面心中央复合设计（FCCCD）观察所选渗透促进剂（巯基乙酸（TGA））和助溶剂（乙醇）对凝胶化行为的影响，以开发具有足够载药量的疏水药物即盐酸特比萘芬（TBN）制剂，并使其在不影响凝胶强度的情况下透过指甲板。结果表明，增加P407和TGA的浓度可显著降低凝胶化温度并提高P407凝胶的凝胶强度，可用于改善P407凝胶强度。在扫描电子显微镜下，观察到TGA作为指甲渗透促进剂对指甲板形态有显著影响。用改良冷法制备的优化P407凝胶的凝胶化温度为8.7±0.16℃，凝胶强度为122±7.5秒，载药量为1.2%，这是用传统冷法制备的凝胶载药量的四倍。流变行为为假塑性，12次洗涤后凝胶侵蚀率为47.75±3.48%，12小时后药物释放率为67.21±2.16%。24小时后，含和不含渗透促进剂的P407凝胶中TBN的累积渗透量分别为27.30±4.18和16.69±2.31μg/cm。巯基乙酸可作为指甲渗透促进剂，无需化学修饰或添加额外添加剂，同时保持凝胶强度。通过对制备方法进行微小改进，可将具有适度挥发性的与水混溶的助溶剂（如乙醇）加入到P407凝胶中，以载入所需剂量的疏水药物。开发的具有足够凝胶强度和载药量的P407凝胶制剂将是经指甲递送疏水抗真菌剂的一种有前景的载体。
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