Course

Unit 1

UNIT-I 9Hrs

Process chemistry

Introduction (1 hr)

Stages of the scale-up process: Bench, pilot, and large-scale process. In-process control and validation of large-scale processes (5 hrs).

Case studies of some scale-up processes of APIs. Impurities in API, types, and their sources, including genotoxic impurities (3 hrs)

Unit 2

UNIT-II 10Hrs

Unit operations

Preliminary Reading: Objectives and basic principles of the following unit operations.

1. Extraction: Liquid equilibria, extraction with reflux, extraction with agitation, counter-current extraction, Supercritical fluid extraction, Microwave-assisted extraction, Ultra Sonication-Assisted Extraction (3 hrs)
2. Filtration: Theory of filtration, pressure and vacuum filtration, centrifugal filtration Ultrafiltration, Magnetic Filtration, Bag Filtration (2 hrs)
3. Distillation: Azeotropic and Molecular distillation (1 hr)
4. Evaporation: Types of evaporators, factors affecting evaporation, Multiple-Effect Evaporators, Thermal Vapour Recompression (TVR), Mechanical Vapour Recompression (MVR) (2 hrs)
5. Crystallization: Crystallization from aqueous, non–aqueous solutions factors affecting crystallization and nucleation. Principle and general methods of Preparation of polymorphs, hydrates, solvates, and amorphous APIs. (3 hrs)

Unit 3

UNIT-III 9Hrs

Unit Processes – I

Preliminary Reading: Introduction and basics of the following unit processes

1. Nitration: Nitrating agents, Aromatic nitration, kinetics and mechanism of aromatic nitration, process equipment for technical nitration, mixed acid for nitration (3 hrs).
2. Halogenation: Kinetics of halogenations, types of halogenations, catalytic halogenations. Case study on industrial halogenation process (3 hrs).

1. Oxidation: Introduction, types of oxidative reactions, Liquid phase oxidation with oxidizing agents. Non-metallic Oxidizing agents such as H2O2, sodium hypochlorite, Oxygen gas, and ozonolysis (3 hrs)

Unit 4

UNIT-IV 8Hrs

Unit Processes – II

1. Reduction: Catalytic hydrogenation, Heterogeneous and homogeneous catalyst; Hydrogen transfer reactions, Metal hydrides. (2 hrs)
2. Fermentation: Aerobic and anaerobic fermentation. Production of
   1. Antibiotics; Penicillin and Streptomycin,
   2. Vitamins: B2 and B12

• Statins: Lovastatin, Simvastatin (3 hrs)

c) Reaction progress kinetic analysis

1. Streamlining reaction steps, route selection,
2. Characteristics of expedient routes, characteristics of cost-effective routes, reagent selection, and families of reagents useful for scale-up. (3 hrs)

Unit 5

UNIT-V 9 Hrs

Industrial Safety

1. MSDS (Material Safety Data Sheet), hazard labels of chemicals, and Personal Protection Equipment (PPE) (3 hrs)
2. Fire hazards, types of fire, and fire extinguishers (2 hrs)

Occupational Health & Safety Assessment Series 1800 (OHSAS–1800) and ISO–14001(Environmental Management System), Effluents and its management (4 hrs)

Assignments:

• Case studies on industrial

• Nitration
• Oxidation
• Reduction process
  • Visit some pharmaceutical companies to understand different unit operations and submit the

• Write an assignment on regulatory requirements in API
• Write a report on MSDS of five hazardous chemicals

The subject is designed to impart knowledge on the development and optimization of a synthetic route/s and the pilot plant procedure for manufacturing Active Pharmaceutical Ingredients (APIs) and new chemical entities (NCEs) for the drug development phase. Process chemistry also focuses on scale-up reactions, taking them from small quantities created in the research lab to the larger quantities that are needed for further testing and then to even larger quantities required for commercial production. It also provides knowledge of organic chemistry, including synthetic methods, reaction mechanisms, and structural analysis, to design efficient synthetic routes for pharmaceutical intermediates and active pharmaceutical ingredients (APIs).

The subject also helps to develop hands-on skills in utilizing advanced laboratory techniques for process optimization, scale-up, and validation and acquire skills in implementing quality control measures to ensure the production of pharmaceuticals meets regulatory standards. It also prepares graduates for diverse roles in pharmaceutical research, development, manufacturing, and regulatory affairs. They are equipped to contribute to the design, optimization, and scale-up of pharmaceutical processes while upholding the highest standards of safety, quality, and compliance.

Upon successful completion of the subject student shall be able to: KNOWLEDGE

K1: Explain the various unit processes in process chemistry.

K2: Demonstrate the fermentation process, involving Aerobic and Anaerobic.

K3: Assess the effectiveness and efficiency of different unit operations in process chemistry through case studies

K4: Optimize reaction progress kinetic analysis by streamlining reaction steps

K5: Evaluate the case studies based on unit processes, and scale up the product.

K6: Design a comprehensive industrial safety protocol for a chemical process, incorporating advanced safety measures and risk assessment techniques.

SKILL

S1: Acquire the ability to scale up chemical processes for the synthesis and manufacturing of pharmaceutical compounds.

S2: Determine the purity of the Organic compounds/APIs by physical and spectroscopy.

S3: Compare the different synthetic mechanisms of active pharmaceutical ingredients.

S4: Assess the challenges related to scale-up, ensuring efficiency and safety in industrial settings

S5: Ensure compliance with regulatory requirements and quality standards in pharmaceutical process development.

S6: Develop proficiency in analytical techniques such as chromatography, spectroscopy, and mass spectrometry for process monitoring and control.

ATTITUDE

A1: Collaborate with teams focused on the development and optimization of pharmaceutical compounds.

A2: Elevate critical thinking skills specifically relevant to the analysis and synthesis of information in the domain of process chemistry.

A3: Develop the ability to critically evaluate and optimize chemical processes for pharmaceutical production.

A4: Foster a commitment to lifelong learning with a specific emphasis on advancements and innovations in process chemistry within the pharmaceutical industry.

A5: Exhibit intrinsic motivation to engage in self-directed learning activities pertinent to process chemistry principles and applications.

A6: Display a proactive approach to problem-solving, specifically in the realm of process chemistry, by addressing challenges encountered in pharmaceutical production.

Reference Books:

1. Peter Harrington: Pharmaceutical Process Chemistry for Synthesis: Rethinking the Routes to Scale- Up, 1^st edition, Volume 2,2011
2. Gadamasetti: Process Chemistry in the Pharmaceutical Industry: Challenges in an Ever-Changing Climate-An Overview; CRC Press,1^st edition, Volume 1,2007
3. William Andrew: Pharmaceutical Manufacturing Encyclopaedia, Elsevier, 3^rd edition, Volume 2,2013
4. Donald J Abraham: Burger’s Medicinal Chemistry, Drug Discovery and Development, Wiley, 8^th edition, Volume 1-8, 2021.
5. L. McCabe, J.C Smith, Peter Harriott: Unit operations of chemical engineering, 7^th edition, McGraw Hill,2005.
6. Harry Brittain: Polymorphism in Pharmaceutical Solids. M. Dekker, New York: 2^nd edition ,1999.
7. Regina Murphy: Introduction to Chemical Processes: Principles, Analysis, Synthesis, McGraw- Hill Higher Education, 2^nd edition,2007.
8. K. Sharma: Industrial Chemistry, Goel Publishing House, 3^rd edition,2005.
9. Unit process in organic synthesis, Groggins, P H, Tata Mc Graw Hill,5^th edition 1995

JOURNALS

1. Organic process research and development(ACS) https://pubs.acs.org/journal/oprdfk
2. Process chemistry (Nature) https://nature.com/subjects/process-chemistry
3. Chemical Engineering Journal (Elsevier) https://sciencedirect.com/journal/chemical-engineering-journal
4. Journal of American Chemical Society (ACS) https://pubs.acs.org/journal/jacsat
5. Processes(MDPI) https://mdpi.com/journal/processes