Computer-Aided Retrosynthesis for Greener and Optimal Total Synthesis of a Helicase-Primase Inhibitor Active Pharmaceutical Ingredient.

This study leverages and upgrades the capabilities of computer-aided retrosynthesis (CAR) in the systematic development of greener and more efficient total synthetic routes for the active pharmaceutical ingredient (API) IM-204, a helicase-primase inhibitor that demonstrated enhanced efficacy against Herpes simplex virus (HSV) infections. Using various CAR tools, several total synthetic routes were uncovered, evaluated, and experimentally validated, with the goal to maximize selectivity and yield and minimize the environmental impact. The CAR tools revealed several synthetic options under different constraints, which can overperform the patented synthetic route used as a reference.

Single and Multiobjective Shutdown Optimization of a Multistage Continuous Crystallizer.

This study presents the first model-based optimal shutdown procedure of a multistage continuous crystallization process which aims at the maximization of on-spec production and minimization of the shutdown time. The cooling antisolvent crystallization of Aspirin (acetylsalicylic acid) in a three-stage continuous crystallizer was used as a case study. To address the optimal shutdown problem, several single optimization scenarios were considered to assess the impact of the degrees of freedom, discretization schemes, and optimization settings such as the constraints.

Use of Wet Milling Combined with Temperature Cycling to Minimize Crystal Agglomeration in a Sequential Antisolvent-Cooling Crystallization.

The objective of the research was to improve the process design of a combined antisolvent-cooling crystallization to reduce the degree of agglomeration of a real active pharmaceutical ingredient product, which was manufactured using a crystallization stage employing a methanol/water solvent system. Knowledge was gained from the use of process analytical technology (PAT) tools to monitor the process variables, allowing particle size, degree of agglomeration, solute concentration, and supersaturation to be tracked throughout the process. Based on knowledge of the solubility behavior and interpretation of the PAT histories, changes were made to the sequences of antisolvent addition and cooling within the crystallization process to reduce agglomeration in the final product.

Versatile reconfigurable glass capillary microfluidic devices with Lego® inspired blocks for drop generation and micromixing.

Novel cost effective, versatile, reconfigurable, reusable and easy to assemble glass capillary microfluidic devices were developed and used to generate micro/nano-materials with controlled size and morphology. The devices are composed of coaxial assemblies of glass capillaries held between two interchangeable plastic blocks fabricated from chemically inert polyoxymethylene copolymer using computer numerical control (CNC) machining. Three different blocks were combined and locked together using Lego® inspired stud-and-hole coupling system to achieve different flow configurations.

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles.

L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer expected to afflict over 53,000 people worldwide by 2020. More recently, ASNase has also been shown to have potential for preventing metastasis from solid tumors. The ASNase treatment is, however, characterized by a plethora of potential side effects, ranging from immune reactions to severe toxicity.

End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis, purification, and final dosage formation.

A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug product in one integrated system.