Purpose

Objective of present work was to develop microfluidic-based technique for continuous production of drug (luliconazole)-loaded microemulsion.

Methods

Pseudo-ternary phase diagrams were constructed, and optimization of concentration of selected formulation components like Capmul MCM, Tween 20 and Transcutol P was done using the Box-Behnken design (BBD). Batch process and microfluidic process were compared in terms of droplet size. Further, microemulsion was loaded into chitosan-based gel, and ex vivo skin permeation study was carried in comparison with marketed formulation.

Results

Optimized batch (ME 1) with Capmul MCM (10% v/v) and mixture of Tween 20 and Transcutol P (32.5% v/v) processed with flow rate of 20 mL/min through microfluidic device exhibited droplet size of 24.9 ± 3 nm (PDI 0.4 ± 0.03). Developed formulation enhanced flux of luliconazole across skin and was stable for 3 months. Increase in volume (20 to 100 mL) for batch process led to corresponding increment in droplet size (from 31.1 ± 11.9 to 56.4 nm) indicating lack of uniformity. Alternatively, for microfluidic device, such alterations in droplet size were avoided.

Conclusion

Achievement of prerequisite droplet size is imperative to colloidal stability of microemulsions and is problematic at larger batch sizes. Batch processes employed are unable to address major issue of uniformity in droplet size and ease of scale up. Experimental findings conclude that as opposed to bath processes, consistent production of microemulsion would be achieved even with higher batch size using microfluidic device. Results strongly advocate further exploration of microfluidic platforms for producing drug-loaded microemulsions.

Graphical Abstract

中文翻译：

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探索微流控平台技术以连续生产药物微乳

目的

当前工作的目的是开发基于微流体的技术，以连续生产载有药物（卢立康唑）的微乳液。

方法

Pseudo-ternary phase diagrams were constructed, and optimization of concentration of selected formulation components like Capmul MCM, Tween 20 and Transcutol P was done using the Box-Behnken design (BBD). Batch process and microfluidic process were compared in terms of droplet size. Further, microemulsion was loaded into chitosan-based gel, and ex vivo skin permeation study was carried in comparison with marketed formulation.

Results

使用Capmul MCM（10％v / v）和Tween 20和Transcutol P的混合物（32.5％v / v）的优化批次（ME 1），通过微流控设备以20 mL / min的流速处理，液滴尺寸为24.9±3纳米（PDI 0.4±0.03）。开发的配方增强了卢立康唑在皮肤上的通量，并稳定了3个月。分批处理的体积增加（20至100 mL）导致液滴尺寸相应增加（从31.1±11.9至56.4 nm），表明缺乏均匀性。或者，对于微流体装置，避免了液滴尺寸的这种改变。

结论

必需的液滴尺寸的实现对于微乳液的胶体稳定性是必不可少的，并且在大批量时是有问题的。所采用的分批工艺无法解决液滴大小均匀性和易于放大的主要问题。实验发现，与浴法相反，即使使用微流控设备以更高的批量生产，也可以实现稳定的微乳液生产。结果强烈提倡对用于生产载药微乳剂的微流体平台的进一步探索。

图形概要