ABOUT THE COURSE:The course will cover all aspects of the subject including crystallization of active pharmaceutical ingredient, intermediates as well as final products. In addition, precipitations and amorphous solids will be covered and the differences between amorphous solids and crystalline solids will be discussed. Solid state pharmaceutics supporting advanced characterization tools are included as well. Upon the completion of the course, student shall be able to apply scientific principles to the design and development of pharmaceutical crystallization processes.INTENDED AUDIENCE: UG PG students interested in pharmaceutical crystal engineering and solid-state pharmaceutical characterizationPREREQUISITES: Basics understanding of crystals, crystal engineering, solid pharmaceutical formulationsINDUSTRY SUPPORT: Pfizer, Novartis, Dr Reddy’s laboratories, Granules India, GSK, MSD, BMS

Syllabus

Week 1:Introduction to various solid-state forms of APIs and their application, Principles of pharmaceutical crystallisation, aims of crystallisation, solubility, turbidity, supersaturation, and the metastable zone and metastable zone width, nucleation and crystal growth
Week 2:Methods of crystallization, cooling crystallisations, evaporative crystallisations, anti-solvent crystallisation and melt crystallisation, crystallisation of chiral compounds/resolution

Week 3:Crystallisation design/case studies, designing a crystallisation process, phase diagrams (binary/ternary), Key crystallization parameters, troubleshooting, Industrial examples

Week 4:Continuous crystallization and continuous manufacturing, Pharma industry 4.0, Basic application of AI/ML in pharmaceutical manufacturing with case studies
Week 5:Polymorphism, polymorph screening, characterising polymorphs, regulatory aspects of polymorphs, and Disappearing polymorphs

Week 6:Co-crystals, the applications of co-crystals, prerequisite criteria in terms of chemistry and physicochemical properties to find an ideal co-former, screening methods, characterization methods, regulatory aspects

Week 7:Solvates and hydrates, characterization of solvates and hydrate, amorphous solids

Week 8:Spectroscopic and diffraction methods of analysing the solid states, Infra-red, Raman, XRPD, Single crystal-XRD, Electron diffraction crystallography (only introduction), identification and differential characterization of physical mixtures, co-crystal and co-amorphous systems
Week 9:Thermal and microscopic methods of analyzing solid-state DSC, TGA, HSM
Week 10:PAT tools, Equipment Considerations and Scale Up
Week 11:Physicochemical characterization of pharmaceutical crystals/co crystals/co-amorphous/solvate/hydrate systems including solubility, powder dissolution, intrinsic dissolution, and mechanical study like indentation, fracture pattern, crack, CTC profiling (compressibility, compactability, Tabletability). Advancements in the solid particle size (sieving. Optical microscopy, electron microscopy, crystallite size by XRD, AI/ML integration, wet/dry methods) and shape (impact of sphericity, aspect ratio, Morphology G4 and other parallel equipment’s) distribution measurements

Week 12:Stability study and formulation development with crystalline materials, Co-processing of active pharmaceutical ingredients, Molecular modelling and simulation studies for polymorphism, crystal habits, amorphous, and co-crystals