Exploring Microfluidic Platform Technique for Continuous Production of Pharmaceutical Microemulsions

Abstract

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

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Abbreviations

DOE:

Design of Experiments

EMG:

Emulgel

BBD:

Box-Behnken design

MIC:

Minimum inhibitory concentration

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Acknowledgements

The authors are also very thankful to Mr. Sanjay Solanki Virdev Intermediates Pvt. Ltd. for providing luliconazole and Mr. Shrikant Dhage (ICT Mumbai) for technical support. Special thanks to Ms. Tejal Pant for the assistance in drafting the manuscript.

Funding

The authors are thankful to the University Grants Commission for the UGC-SAP fellowship (F.25–1/2014–15 [BSR]/No. F.8–10/2007[BSR]), (SR/NM/NS-1145/2012-ICT) and DAE-ICT for financial support.

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Correspondence to Prajakta Dandekar or Ratnesh Jain.

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Patil, S., Pandit, A., Gaikwad, G. et al. Exploring Microfluidic Platform Technique for Continuous Production of Pharmaceutical Microemulsions. J Pharm Innov (2020). https://doi.org/10.1007/s12247-020-09457-x

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Keywords

  • Microemulsion
  • Microfluidic reactor
  • Luliconazole
  • Continuous manufacturing
  • Design of experiments