Process development
A.A. 2021/2022
Obiettivi formativi
The goal of this course is to provide an insight into organic process research and development for the preparation of Active Pharmaceutical Ingredients (APIs) and relevant intermediates from laboratory to commercial scale. In particular, emphasis will be put on the theoretical basis for a correct approach to a safe, green, reliable, reproducible and cost-effective process.
Risultati apprendimento attesi
At the end of the course, the students will be able to plan the development of a synthetic procedure taken from the literature, to design and fill the corresponding block flow diagram.
Periodo: Secondo semestre
Modalità di valutazione: Esame
Giudizio di valutazione: voto verbalizzato in trentesimi
Corso singolo
Questo insegnamento non può essere seguito come corso singolo. Puoi trovare gli insegnamenti disponibili consultando il catalogo corsi singoli.
Programma e organizzazione didattica
Edizione unica
Teaching methods:
More specific information on the delivery modes of training activities for academic year 2021/2022 will be provided over coming months, based on the public health situation.
Course syllabus and Teaching Resources:
Attending students must refer to the contents and reference material already reported in the program in addition to the materials and resources published in the online course.
Assessment methods and Criteria:
Only in the case of emergency remote teaching, the final exam will be an oral test through the Microsoft Teams platform according to the indications provided by the University. The students will be divided into small groups (Teams) and the calendars of the oral examinations will be published and constantly updated in the online course. Duration of the oral test: normally 40-45 min.
The oral test will aim to ascertain the achievement of the objectives in terms of knowledge and understanding. In particular, the evaluation criteria will focus on the ability to plan the development of a single reaction step synthesis of an active pharmaceutical ingredient (API) (or of a relevant intermediate taken from the recent literature), taking into account key parameters such as safety, environmental impact (atom economy and E-factor), reliability, and cost-effectiveness. The student's ability to prepare the corresponding block flow diagram will be also assessed.
The final mark of the test will be expressed in thirtieths and the result published on the dedicated page of the UNIMI website, leaving the student the possibility of accepting it or not.
More specific information on the delivery modes of training activities for academic year 2021/2022 will be provided over coming months, based on the public health situation.
Course syllabus and Teaching Resources:
Attending students must refer to the contents and reference material already reported in the program in addition to the materials and resources published in the online course.
Assessment methods and Criteria:
Only in the case of emergency remote teaching, the final exam will be an oral test through the Microsoft Teams platform according to the indications provided by the University. The students will be divided into small groups (Teams) and the calendars of the oral examinations will be published and constantly updated in the online course. Duration of the oral test: normally 40-45 min.
The oral test will aim to ascertain the achievement of the objectives in terms of knowledge and understanding. In particular, the evaluation criteria will focus on the ability to plan the development of a single reaction step synthesis of an active pharmaceutical ingredient (API) (or of a relevant intermediate taken from the recent literature), taking into account key parameters such as safety, environmental impact (atom economy and E-factor), reliability, and cost-effectiveness. The student's ability to prepare the corresponding block flow diagram will be also assessed.
The final mark of the test will be expressed in thirtieths and the result published on the dedicated page of the UNIMI website, leaving the student the possibility of accepting it or not.
Programma
Course program with the chronological order of the lessons:
Aim of the course, course content, assessment method. Scale-up issues: reaction vessels, separation, volume measurements, sampling, evaporation to dryness, temperature control, isolation of solid products, etc. Characteristics of cost-effective route: convergent vs. linear syntheses, telescoping, number of steps, productivity, catalytic vs. stoichiometric approaches, linear and convergent syntheses. Different synthetic practical approaches (chirality pool, separation of stereoisomers: resolution, crystallization and racemization). The SELECT criteria: Safety, Environmental, Legal, Economics, Control, Throughput issues. Safety issues related to thermochemistry in view of designing intrinsically safe processes thus avoiding runaway reactions, thermal decompositions. Methods and instruments for thermal-hazard testing (DSC; TGA; ARC; RC) and data analysis. Reaction criticality class: the Stoessel diagram and its interpretation. Route selection: Green Chemistry and chemistry metrics (yields, conversion, selectivity, E-factor, atom economy theory, reaction mass efficiency, molecular complexity, etc.). Sustainable processes: the development of awarded environmentally benign syntheses. Solvents for large scale operation: toxicity and flammability. Standards of choice. Alternative to classical solvents: water, supercritical CO2, ionic liquids, deep eutectic solvents, reaction without solvent. Solvent recycles. Solvent swap (replacement, chase). Process development and analytical issues: determination of purity and assay of starting materials, solvents, intermediates, APIs. In-process controls (IPC)s. Choosing the appropriate, reliable and reproducible IPC. Reagents for large scale operation: toxicity and flammability, ease of handling. Standards of choice. Pharmaceutical company Reagent Selection Guides. Work-up: definition and purposes. Aspect of work-up: quench, extraction, activated carbon treatment, filtration, concentrating solution and solvent displacement, deionization and metals removal, process stream destruction, derivatization. Economics: direct, indirect, fix and variable costs to design a competitive process. Exercises on case studies taken from literature. Use of worksheet and block flow diagram.
Aim of the course, course content, assessment method. Scale-up issues: reaction vessels, separation, volume measurements, sampling, evaporation to dryness, temperature control, isolation of solid products, etc. Characteristics of cost-effective route: convergent vs. linear syntheses, telescoping, number of steps, productivity, catalytic vs. stoichiometric approaches, linear and convergent syntheses. Different synthetic practical approaches (chirality pool, separation of stereoisomers: resolution, crystallization and racemization). The SELECT criteria: Safety, Environmental, Legal, Economics, Control, Throughput issues. Safety issues related to thermochemistry in view of designing intrinsically safe processes thus avoiding runaway reactions, thermal decompositions. Methods and instruments for thermal-hazard testing (DSC; TGA; ARC; RC) and data analysis. Reaction criticality class: the Stoessel diagram and its interpretation. Route selection: Green Chemistry and chemistry metrics (yields, conversion, selectivity, E-factor, atom economy theory, reaction mass efficiency, molecular complexity, etc.). Sustainable processes: the development of awarded environmentally benign syntheses. Solvents for large scale operation: toxicity and flammability. Standards of choice. Alternative to classical solvents: water, supercritical CO2, ionic liquids, deep eutectic solvents, reaction without solvent. Solvent recycles. Solvent swap (replacement, chase). Process development and analytical issues: determination of purity and assay of starting materials, solvents, intermediates, APIs. In-process controls (IPC)s. Choosing the appropriate, reliable and reproducible IPC. Reagents for large scale operation: toxicity and flammability, ease of handling. Standards of choice. Pharmaceutical company Reagent Selection Guides. Work-up: definition and purposes. Aspect of work-up: quench, extraction, activated carbon treatment, filtration, concentrating solution and solvent displacement, deionization and metals removal, process stream destruction, derivatization. Economics: direct, indirect, fix and variable costs to design a competitive process. Exercises on case studies taken from literature. Use of worksheet and block flow diagram.
Prerequisiti
Courses of Organic Chemistry I and Organic Chemistry II passed. Basic concepts of Organic Chemistry.
Metodi didattici
Lectures and exercises on case studies taken from literature.
Materiale di riferimento
- Practical Process Research & Development - Neal G. Anderson - Academic Press, Elsevier
- Green Chemistry in Pharmaceutical industry - Peter J. Dunn et al. Wiley-VCH 2010
- Lesson slides and videos (in the case of emergency remote teaching).
- Green Chemistry in Pharmaceutical industry - Peter J. Dunn et al. Wiley-VCH 2010
- Lesson slides and videos (in the case of emergency remote teaching).
Modalità di verifica dell’apprendimento e criteri di valutazione
Written test. Duration: normally 2.5 hours
The written test foresees a critical analysis of a single reaction step synthesis of an active pharmaceutical ingredient (API) or of a relevant intermediate taken from the recent literature.
The ability: 1) to plan the development of the synthetic procedure, taking into account key parameters such as safety, environmental impact (atom economy and E-factor), reliability, and cost-effectiveness, and 2) to prepare the corresponding block flow diagram will be evaluated.
The final mark of the test will be expressed in thirtieths and the result published on the dedicated page of the UNIMI website, leaving the student the possibility of accepting it or not.
The written test foresees a critical analysis of a single reaction step synthesis of an active pharmaceutical ingredient (API) or of a relevant intermediate taken from the recent literature.
The ability: 1) to plan the development of the synthetic procedure, taking into account key parameters such as safety, environmental impact (atom economy and E-factor), reliability, and cost-effectiveness, and 2) to prepare the corresponding block flow diagram will be evaluated.
The final mark of the test will be expressed in thirtieths and the result published on the dedicated page of the UNIMI website, leaving the student the possibility of accepting it or not.
CHIM/04 - CHIMICA INDUSTRIALE - CFU: 6
Lezioni: 48 ore
Docente:
Manfredi Amedea Giuseppina