University of Toronto, Ontario.
J Pharm Pharm Sci. 2011;14(3):315-24. doi: 10.18433/j38p4v.
To develop and characterize low-surfactant microemulsion (ME) gels to enhance topical delivery of poorly soluble drugs.
Five low surfactant ME formulations were manufactured following the construction of pseudo-ternary phase diagrams. The MEs were screened for their ability to dissolve a poorly soluble new chemical entity (Model Drug X). Various viscosity imparting agents like Carbopol 934, Colloidal Silica, HPMC K100M, Lubrajel NP, and Xanthan Gum were evaluated for the manufacture of these ME gels. Each ME gel was then further evaluated for physical stability, including assessing rheological profiles. In vitro release profiles were also determined and compared to a conventional ointment.
Three of the five low surfactant MEs developed (ME1, ME4 and ME5) were capable of dissolving Model Drug X up to 14 fold higher than the conventional ointment formulation. ME1 and ME4 gels comprising Xanthan gum or Carbopol 934 were physically stable, while ME5 gel was stable only with Colloidal Silica. The ME5 gel with Colloidal Silica showed an irreversible increase in its elastic modulus when exposed to high temperature, indicating that the formulation would be less suitable for commercial use. The Xanthan Gum and Colloidal Silica gels yielded significantly higher release rates (8 - 10 fold) compared to a conventional ointment and formulations containing Carbopol 934. The significant difference in drug release rates between Xanthan Gum and Carbopol 934 indicated that choice of viscosity imparting agent played an important role in governing drug release from ME gels.
ME gels were developed with low surfactant concentrations and improved formulation characteristics, which increased the solubility and subsequent release of a poorly soluble drug. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
开发并表征低表面活性剂微乳（ME）凝胶，以增强难溶性药物的局部递送。
根据伪三元相图的构建，制造了五种低表面活性剂 ME 制剂。筛选 ME 溶解一种新的难溶性化学实体（模型药物 X）的能力。评估了各种赋予粘度的物质，如 Carbopol 934、胶体二氧化硅、HPMC K100M、Lubrajel NP 和黄原胶，以制造这些 ME 凝胶。然后进一步评估每个 ME 凝胶的物理稳定性，包括评估流变学特性。还测定了体外释放曲线，并与常规软膏进行了比较。
开发的五种低表面活性剂 ME 中的三种（ME1、ME4 和 ME5）能够将模型药物 X 的溶解度提高 14 倍以上，高于常规软膏制剂。包含黄原胶或 Carbopol 934 的 ME1 和 ME4 凝胶具有物理稳定性，而仅含有胶体二氧化硅的 ME5 凝胶是稳定的。当暴露于高温时，含有胶体二氧化硅的 ME5 凝胶的弹性模量不可逆地增加，表明该制剂不太适合商业用途。与常规软膏和含有 Carbopol 934 的制剂相比，黄原胶和胶体二氧化硅凝胶的释放速率显著提高（8-10 倍）。黄原胶和 Carbopol 934 的药物释放速率的显著差异表明，选择赋予粘度的物质在控制 ME 凝胶中药物释放方面起着重要作用。
开发了具有低表面活性剂浓度和改进配方特性的 ME 凝胶，增加了难溶性药物的溶解度和随后的释放。本文接受 POST-PUBLICATION REVIEW。注册读者（请参阅“读者须知”）可以在问题的内容页面上点击 ABSTRACT 进行评论。
