Paving The Road from Small- to Large-scale Production of Green Nano Pharmaceuticals.

Introduction

Nanotechnology has successfully invaded medical science, especially in drug delivery field. Despite the huge advances achieved in the field of nanomedicines on laboratory scale, a limited number of nanotechnology-based drugs are available in the global market​. This is because hazardous chemicals are frequently used in conventional nanoparticle synthesis methods. The goal of this study was to investigate novel, easily scalable, environmentally friendly methods to prepare drug-loaded nanoparticles on a pilot-scale without using toxic organic solvents. Additionally, to locally design, develop, and optimize prototype pilot scale equipment for nanoparticle synthesis as a means of creating a bridge between laboratory and industrial scales.

Methods

Carbamazepine-loaded transfersomes (CZTs), a type of lipid-based nanoparticles, were prepared on a small scale using the modified scalable heating method that avoids organic solvents usage and high energy procedures (green synthesis) in a specially designed homemade vessel replicating Mozafari’s containing baffles forming many turbulences leading to formation of nanosized particles​. A three-factor, three-level Box-Behnken design was employed to optimize process and formulation factors. Furthermore, the optimized formulation was synthesized on both a small-scale and pilot-scale via the modified heating method.

Results

The small-scale beaker simulating Mozafari’s was successfully scaled up to a pilot-scale tank of large capacity (13 Liters) compared to the small-scale beaker of capacity 50 milliliters only. Consistent results were observed for the optimized formula on both small and pilot-scale showing a mean size of 323.12±0.3 nm and 341.5±1.4 respectively, a high entrapment efficiency (EE) of 76.12±1.1% and 75.01± 0.5% respectively, and a sustained release profile.

Conclusion

CZTs optimized formulation was successfully fabricated on both small- and pilot-scale using a simple, scalable, green, modified heating method. Box–Behnken surface analysis proved to be an efficient tool to optimize the CZTs formulations. CZTs fabricated on the two scales possessed comparable results.

https://www.youtube.com/watch?v=FWOMPJhLTDQ