MEDICINE Pharmaceuticals The Engineering Grand Challenges and Green

MEDICINE (Pharmaceuticals) The Engineering Grand Challenges and Green Engineering

NAE. Grand Challenges for Engineering 2008 http: //www. engineeringchallenges. org/challenges/medicines. aspx

Pharmaceuticals industry EFPIA. The Pharmaceutical Industry in Figures: Key Data 2016

Creating pharmaceuticals is inefficient • Depends on what is termed as “waste” • Can be split into sub-categories; o Organic waste o Aqueous waste • The smaller the number, the closer to zero waste Sheldon, R. Green Chem. 2007

Green Engineering Research in Pharma Key green engineering research areas Jimenez-Gonzalez, C. OPRD 2011

Continuous processing in process intensification • • • Reduce costs Reduce the size of process equipment, Improve product quality Reduce energy consumption, solvent utilization Decrease waste generation Increase process safety Jimenez-Gonzalez, C. OPRD 2011

Green Engineering Principles • Principle 5: “Output-pulled” rather than “inputpushed” • Principle 1: Inherent rather than circumstantial • Principle 3: Design for separation • Principle 9: Minimize material diversity

Principle 5: “Output-pulled” vs. “input-pushed” “Drive” a reaction or transformation to completion by adding materials or energy. A+B C+D Similarly, a reaction can be “pulled” to completion by removing the product without adding materials or energy. A+B C+D

Principle 5 example: Reactive distillation Taylor, R. Chem. Eng. Sci 2000

Unit operations in pharma synthesis Separations Jimenez-Gonzalez, C. OPRD 2011

Reactions and Separations • Materials Use: Separations contribute 40 -90% of the process mass intensity of a synthesis. • Energy Use: Distillation and drying steps alone often consume >50% process energy • Time and cost: These steps are typically also process bottlenecks leading to predominant contributions to time and cost Jimenez-Gonzalez, C. OPRD 2011

Solvents • Usage: – – – Dissolution Suspension Extraction/purification Reaction medium Formulation/ product delivery • Examples: isopropanol, hexane, chloroform • Strategies for solvent reduction – REDUCE, REUSE, RECYCLE Jimenez-Gonzalez, C. OPRD 2011

Principle 1: Inherent rather than circumstantial • Some traditional solvents – Diethyl ether, an explosive and extremely flammable solvent, was used for anesthesia—until doctors tired of explosions at the operating table and the resulting fatalities. – Dichloromethane, a potent environmental polluter, is another solvent of concern, especially due to its high volatility. It is often used in paint thinners, but despite its relatively low toxicity, it has caused over 50 deaths since 1980 in the US alone

Needs for green solvents Metrics of a green solvent: • Toxicity, safety, hazard • Energy use, environmental metrics, life cycle metrics – Method and ease of recycling – Ease of separation – Depends on properties (ex: volatility, viscosity, stability) Tactics: Find better existing alternatives Neoteric alternatives Jimenez-Gonzalez, C. OPRD 2011

Soh, L. ACS Sust Chem Eng 2016 Identifying green solvents

Life cycle inherent hazard Soh, L. ACS Sust Chem Eng 2016

Energy use for solvent production Jessop, P. Green Chem 2011

Solvent CO 2 emissions Jessop, P. Green Chem 2011

Example: Pfizer green solvent guide Alfonsi, K. Green Chem 2008

Alternatives must be functional Soh, L. ACS Sust Chem Eng 2016

Glaxo. Smith. Kline Solvent classification affects both utility and sustainability Alder, C. Green Chem. 2016

Principle 3: Design for separation • Can solvents be designed to minimize impacts associated with separation? • Can systems be designed to allow for separation without solvents? Capello, C. Green Chem 2007

Designing for separations Jessop, P. Green Chem 2011

Principle 9: Minimize material diversity • Allows for easier recycling and reuse • Simplifies processing

Supercritical fluid assisted drug delivery No residuals Single solvent use Reverchon, E. J. Supercritical Fluids. 2009

Solvent free reactions? - Mechanochemistry • Mechanochemistry uses physical force for chemical reaction Example of mechanochem for polymer elongation: May 2013 Chem. Soc. Rev Example of motion in a ball mill: Garay 2007. Chem. Soc. Rev Sample ball mills: Šepelák 2013. Chem. Soc. Rev

Case study: Sildenafil citrate Dunn, P. Green Chem. 2004

Reduce waste from new production process Dunn, P. Green Chem. 2004

Summary • The pharmaceuticals industry currently produces much waste leading to inflated economic and environmental impacts • Green engineering principles may be applied to decrease cost and impacts • Green solvents are a growing field that can be investigated for more efficient pharmaceuticals production

IDEO – The Deep Dive (moodle) Watch the posted video on Moodle and discuss with your group members: • How does the process differ from your typical thoughts on design? • How can you utilize the tactics employed for your process? Include these thoughts in your first project update on design alternatives (due March 22)