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Electron Microscopy Sciences

EMS Microscopy Academy Applications

Workshop Information

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arrow13Pharmaceutical Microscopy Workshop: Polymorphism

This workshop covers the use of the microscope in both early pharmaceutical development when the form is chosen and in later stages of development where the form is monitored for stability.

Examples of the Microscopy of Pharmaceuticals

Caffeine Form 2 by polarized light microscopy with crossed polars and a full lambda waveplate. The large blue particle is cellulose.
Caffeine Hydrate by SEM. Caffeine hydrate readily converts to the metastable Form 1 which, in turn, converts readily to Form 2 - the stable form at ambient conditions.

RG12525 Form 1 by SEM. The Form 1 habit is acicular and could not be altered using any of the attempted recrystallization techniques. Milling produced small fibers with poor flow properties.
RG12525 Form 2 by SEM. The Form 2 habit is twinned blocks. Milling produced small irregular particles with good flow properties.

Fusion of acetyl salicylic acid with phenactin. Acetylsalicylic acid is on the right and phenactin on the left. The eutectic forms in the middle mixing zone.
Schematic energy vs. temperature diagram for three polymorphs. Forms I and II are enantiotropically related whereas forms I and III are monotropically related. Forms II and III are also are also monotropically related. Thermal microscopy can be used to generate such diagrams.

Benzyl fusion preparation by PLM in crossed polars. Benzyl exhibits anomalous interference colors which can be used for form identification purposes.
Image of trehalose anhydrate from the melt of trihydrate. Polarized light microscopy with polars and full lambda waveplate.


The EMS Microscopy Academy
Located in Hatfield, Pennsylvania, the Academy provides electron microscopy classes, workshops and training sessions for all fields of microscopy, including materials science and biological science.

Targeted Participants

This course is designed for the skilled analyst who is familiar with the basic pharmaceutical microscopy instruments. The emphasis of the workshop is on the practical application of microscopy in the analysis of polymorphism.

Scope of Class

The choice of the optimum solid-state form is critical for successful pharmaceutical development. Broadly defined, form includes polymorphs, hydrates, solvates, salts, co-crystals etc. Microscopy is well- suited to the study of solid-state form.

This workshop covers the use of the microscope in both early pharmaceutical development when the form is chosen and in later stages of development where the form is monitored for stability.

It covers the material in Chapter 8 Pharmaceutical Microscopy (Springer, 2011) along with selections from other chapters. The course emphasizes how microscopy is used in conjunction with other analytical techniques for form selection and analysis.


Lecture, demonstration and hands-on practice, as well as round table table tips and tricks discussion. Participants are encouraged to bring their own samples, if possible.

Main Curriculum

The material in this workshop is broadly separated by development phase into form discovery and form understanding. Form discovery usually occurs before first time in human (FTIH) into Phase 1. Form understanding generally occurs in Phase 1 and Phase 2, although some work extends into Phase 3.

This workshop emphasizes the role of microscopy in each aspect of form understanding. Although we will discuss solid-state theory and fundamentals, the workshop relies heavily on case studies, demonstrations, and instrument usage.

Instruments Available

Polarizing Light Microscope Hitachi S3500 SEM Image Analysis Software
Linkam Thermal Microscope Bruker Esprit (SDD) IR and Raman Microscopes


Robert Carlton
Robert worked for nearly 40 years in the research and development of fiberglass insulation, orthopedics, and pharmaceuticals. His specialty is solid-state analysis with a particular interest in microscopy. Robert retired from full-time employment in early 2016. He is now teaching microscopy and consulting on solid-state analysis in pharmaceutical development. Robert's education is in chemistry, with a Ph.D. from Lehigh University. He has taken numerous courses at McCrone Research Institute on microscopy from Skip Palenik and Walter McCrone. Robert worked for pharmaceutical companies Rhone-Poulenc Rorer (Aventis, Sanofi), Elan (Nanocrystal), and GlaxoSmithKline in microscopy and solid-state analysis for 24 years. He published a book on Pharmaceutical Microscopy in 2011 with Springer.

Michael Kostrna
Michael was the program director of the Electron Microscopy Technician program at Madison Area Technical College and has more than 35 years in EM technical education and research experience. He has been training EM students for 29 years and has developed curricula and lab exercises for TEM, SEM, OLM, lab safety, introductory and advanced biological EM, EM, maintenance, and x-Ray microanalysis. He has worked with companies such as SC Johnson Polymer, Dow Chemicals, Io Genetics, Virent Technologies, ABS Global, NanoOnocology, and Microscopy Innovations, and in the process gained insight to the various applications of EM.

Al Coritz
Al has been working in the Electron Microscopy field for 38 years, beginning at the Yale School of Medicine and ending up on the commercial side with several key EM companies. His specialty is Cryo-techniques and Thin Film Technology: i.e. Freeze Fracture/Rotary Shadowing, High Pressure Freezing, and more. He is currently with Electron Microscopy Sciences where he has been the Technical Director for over 20 years.

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