3D printing and continuous flow chemistry technology to advance pharmaceutical manufacturing in developing countries

Abstract

The realization of a downward spiralling of diseases in developing countries requires them to become self-sufficient in pharmaceutical products. One of the ways to meet this need is by boosting the local production of active pharmaceutical ingredients and embracing enabling technologies. Both 3D printing and continuous flow chemistry are being exploited rapidly and they are opening huge avenues of possibilities in the chemical and pharmaceutical industries due to their well-documented benefits. The main barrier to entry for the continuous flow chemistry technique in low-income settings is the cost of set-up and maintenance through purchasing of spare flow reactors. This review article discusses the technical considerations for the convergence of state-of-the-art technologies, 3D printing and continuous flow chemistry for pharmaceutical manufacturing applications in developing countries. An overview of the 3D printing technique and its application in fabrication of continuous flow components and systems is provided. Finally, quality considerations for satisfying regulatory requirements for the approval of 3D printed equipment are underscored. An in-depth understanding of the interrelated aspects in the implementation of these technologies is crucial for the realization of sustainable, good quality chemical reactionware.

Application of reactor engineering concepts in continuous flow chemistry: a review

“…Based on a brief overview of different 3D printing methods and materials, we have chosen to highlight a few papers describing some of these method applications in microfluidics here. 10,144,145 5.1 3D printed microchannel flow devices. Rossi and coworkers fabricated a 3D printed mesoflow reactor from polyacetic acid (PLA), high impact polystyrene (HIPS) and nylon, which was used for a catalytic stereoselective Henry type reaction.…”

Rapid Multigram-Scale End-to-End Continuous-Flow Synthesis of Sulfonylurea Antidiabetes Drugs: Gliclazide, Chlorpropamide, and Tolbutamide

“…37,38 The technology has several benefits over the conventional batch process such as faster reactions, better mixing, ease scale, cleaner products, efficient mass, and heat transfer. [39][40][41][42][43] By exploiting continuous-flow technology, we demonstrate herein high throughput continuous-flow syntheses of sulfonylureas 1 [gliclazide (1a), chlorpropamide (1b), and tolbutamide (1c)] (Figure 1). In this present work, the sulfonylurea moiety was constructed through the condensation of a carbamate 2 intermediate with sulfonamide 3 (Scheme 2).…”

Towards 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients

“…It is increasingly gaining attention and is embraced from academic research to pharmaceutical research and development, as well as manufacturing, due to its associated advantages over the traditional batch processes. 1–6 The possibility of integrating multiple reaction steps into a single continuous flow has attracted great interest in the syntheses of active pharmaceutical ingredients (APIs), natural products and commodity chemicals as it avoids the tedious and time consuming intermediate isolation; 1,2 however that usually requires the use of diverse solvents, inline separation and purification of the intermediate reactions and even quenching during the process. This has proven to be a challenge when telescoping the individual optimised steps.…”