Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
Int J Pharm. 2022 Nov 25;628:122327. doi: 10.1016/j.ijpharm.2022.122327. Epub 2022 Oct 21.
Metronidazole (MNZ) is a nitroimidazole derivative antibiotic that has been generally used in the treatment of rosacea. However, it has low molecular weight and lipophilicity, limiting the effectiveness of MNZ in the topical treatment of rosacea. This study reports an MNZ-loaded solid lipid microparticle (SLM) gel formulation with sustained drug release effects required in the treatment of rosacea. SLM was formulated using the double emulsification method with five different concentrations of glyceryl monostearate (GMS) as a solid lipid used to encapsulate MNZ. All the MNZ-loaded SLM formulas were extensively characterized by various analytical tools. After optimized MNZ-loaded SLM formulation was obtained, then formulated into gel preparation. To obtain a gel formula with good physical characteristics and drug release in the development of topical therapy, the SLM-loaded gel was further evaluated, covering various parameters such as pH, viscosity, rheology, spreadability, extrudability, skin occlusivity, gel strength, permeation and retention ex vivo, as well as hemolysis tests and antioxidant activity. The evaluation results showed that the SLM formulations had desired properties with optimum encapsulation efficiency. Moreover, the gels prepared from carbomer possessed desired characteristics and were found to be hemocompatible. In addition, the gel formula with a carbomer concentration of 1.25 % can provide better drug release with the highest MNZ retention after 24 h of 2.35 ± 0.05 mg. Notably, the formulation of MNZ into SLM and hydrogel did not affect the antioxidant activity. Thus, it can provide continuous drug release, which could potentially be useful in increasing efficacy in rosacea therapy. The results obtained also showed a significant difference (p < 0.05) compared to the control formula and other formulas. Therefore, this study has proven a new approach to developing drug delivery systems for rosacea treatment.
甲硝唑（MNZ）是一种硝基咪唑类衍生抗生素，通常用于治疗酒渣鼻。然而，它的分子量低且亲脂性差，限制了 MNZ 在酒渣鼻局部治疗中的效果。本研究报告了一种载有 MNZ 的固体脂质微球（SLM）凝胶制剂，该制剂具有治疗酒渣鼻所需的持续药物释放效果。SLM 是通过双乳化法用五种不同浓度的单硬脂酸甘油酯（GMS）作为固体脂质来包封 MNZ 而制成的。所有载有 MNZ 的 SLM 配方均通过各种分析工具进行了广泛的表征。在获得优化的载有 MNZ 的 SLM 配方后，将其进一步制成凝胶制剂。为了获得在局部治疗开发中具有良好物理特性和药物释放的凝胶配方，进一步评估了载有 SLM 的凝胶，涵盖了各种参数，如 pH 值、粘度、流变学、铺展性、挤出性、皮肤封闭性、凝胶强度、体外渗透和保留、溶血试验和抗氧化活性。评估结果表明，SLM 制剂具有理想的性质和最佳的包封效率。此外，由卡波姆制备的凝胶具有理想的特性且具有血液相容性。此外，当卡波姆浓度为 1.25%时，载有 MNZ 的凝胶配方在 24 小时后可以提供更好的药物释放，最高 MNZ 保留量为 2.35±0.05mg。值得注意的是，将 MNZ 配方成 SLM 和水凝胶不会影响其抗氧化活性。因此，它可以提供持续的药物释放，这可能有助于提高酒渣鼻治疗的疗效。与对照配方和其他配方相比，研究结果也显示出显著差异（p<0.05）。因此，本研究为开发治疗酒渣鼻的药物传递系统提供了一种新方法。
