Pharmaceutical Process Chemistry

THEORY 1.

Process chemistry Introduction, Synthetic strategy Stages of scale up process: Bench, pilot and large scale process.

In-process control and validation of large scale process.

Case studies of some scale up process of APIs.

Impurities in API, types and their sources including genotoxic impurities Hrs Unit operations a) Extraction:

Liquid equilibria, extraction with reflux, extraction with agitation, counter current extraction.

b) Filtration: Theory of filtration, pressure and vacuum filtration, centrifugal filtration, c) Distillation: azeotropic and steam distillation d) Evaporation: Types of evaporators, factors affecting evaporation.

e) Crystallization:

Crystallization from aqueous, non- aqueous solutions factors affecting crystallization, nucleation. Principle and general methods of Preparation of polymorphs, hydrates, solvates and amorphous APIs.

Hrs Unit Processes - I a) Nitration: Nitrating agents, Aromatic nitration, kinetics and mechanism of aromatic nitration, process equipment for technical nitration, mixed acid for nitration, b) Halogenation:

Kinetics of halogenations, types of halogenations, catalytic halogenations. Case study on industrial halogenation process.

c) Oxidation: Introduction, types of oxidative reactions, Liquid phase oxidation with oxidizing agents. Nonmetallic Oxidizing agents such as H2O2, sodium hypochlorite, Oxygen gas, ozonolysis.

Hrs Unit Processes - II a) Reduction:

Catalytic hydrogenation, Heterogeneous and homogeneous catalyst; Hydrogen transfer reactions, Metal hydrides. Case study on industrial reduction process.

b) Fermentation:

Aerobic and anaerobic fermentation.

Production of i.

Antibiotics; Penicillin and Streptomycin, ii. Vitamins: B2 and B12 iii. Statins: Lovastatin, Simvastatin c) Reaction progress kinetic analysis i. Streamlining reaction steps, route selection, ii. Characteristics of expedient routes, characteristics of cost-effective routes, reagent selection, families of reagents useful for scale-up.

Hrs Industrial Safety a) MSDS (Material Safety Data Sheet), hazard labels of chemicals and Personal Protection Equipment (PPE) b) Fire hazards, types of fire & fire extinguishers c) Occupational Health & Safety Assessment Series 1800 (OHSAS-1800) and ISO-14001(Environmental Management System), Effluents and its management Hrs