Haslam Special Topics in Formulation Series (2023)

Inaugural Series Lecturer

Gregory Amidon, Ph.D.

Fellow of the American Association of Pharmaceutical Scientists (AAPS); AAPS President;  2014 AAPS Research Achievement Award in Physical Pharmacy and Biopharmaceutics; 2015 Champion of Quality Award from USP; Ebert Prize from the American Pharmaceutical Association. UofM Faculty, Pfizer, Pharmacia, Upjohn

Course Overview

With the ever-increasing need for development speed, accuracy, and consistency, the ability to complete a thorough characterization of materials and formulations is critical - and it is possible. Thorough characterization of formulation components (both the API and excipients) is a valuable precursor to initiating solid dosage form development activities.  Physical, chemical, and mechanical properties provide key information and insight needed to select ingredients and unit processes. This short course will provide a greater understanding of the basic science and importance of the properties of solids and mechanical property characterization (i.e. properties of a material under an applied stress) with a focus primarily on solid dosage formulation development. Both dynamic, high-speed, mechanical property and quasi-static testing, many based on basic engineering testing approaches, will be discussed as tools to advanced formulation science, design, and development. Complimentary tools provide a valuable set of information upon which to make material, formulation, and process decisions. Thorough characterization of formulation components is a necessary precursor to a robust Quality by Design (QbD) approach favored by the FDA.  This approach provides data that allows the formulator to design and monitor changes throughout development, identify critical material attributes, process parameters, and set meaningful critical product attributes. Thorough physical, chemical, and mechanical property characterization at every step of the development and manufacturing process facilitates the development of robust and well-characterized formulations. This integrative process moves formulation development away from “guided empiricism” to a data-driven and predictive science leading to dosage forms that can be successfully manufactured and easily scaled up. Early, meaningful characterization using small quantities of material is not only possible – it is valuable.

Outline

1. Introduction to the properties of solids and solid dose manufacturing
2. Fundamental Forces and Assemblies of Particles                  
3. Concepts of Stress, strain, shear                                          
4. Elastic, plastic deformation as fundamental properties & processes 
5. Mechanical Property Characterization: Quasi-static & Dynamic Methods      
6. Active Pharmaceutical Ingredient Properties           
7. The Compaction Process                                                    
8. Properties of mixtures and solid formulation design
9. Unit Processes, Continuous Manufacturing, Critical Material Attributes, Quality by Design    
10. Powder Flow: Practical methods & Shear cell basics             
11. Material Sparing Methods of Formulation Design and Development

Optional Discussions

• Physicochemical characterization / Drug Development process, Networks / Regulatory sciences/issues

Key References:

1. Dening TJ, Amidon GE, He X, Hageman MJ. Physicochemical Characterization and Oral Dosage Form Design and Selection. In: Abraham DJ, editor. Burger’s Medicinal Chemistry, Drug Discovery and Development: John Wiley & Sons, Inc; 2019.
2. Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding Pharmaceutical Quality by Design. The AAPS Journal. 2014;16(4):771-783.
3. Amidon GE, Meyer PJ, Mudie DM. Particle, Powder, and Compact Characterization. In: Qiu Y, Chen Y, Zhang GGZ, Yu L, Mantri RV, editors. DEVELOPING SOLID ORAL DOSAGE FORMS: Oxford Academic Press; 2016. p. 271-294.
4. Rohrs BR, Amidon GE, Meury RH, Secreast PJ, King HM, Skoug CJ. Particle size limits to meet USP content uniformity criteria for tablets and capsules. Journal of Pharmaceutical Sciences. 2006;95(5):1049-1059.
5. Amidon GE. Oral Solid Dosage Forms. In: Sinko P, editor. Martin's Physical Pharmacy and Pharmaceutical Sciences: 6th Edition; Wolters Kluwer; 2011. p. 563-593.

Registration

• All participants are required to register.
• KU Researchers and Industrial Affiliates - There is no charge for attending this formulation series, but a suggested donation of $250 per person to the “Haslam Fund for Formulation Education and Research in Pharmaceutical Chemistry” fund via KU Endowment would be greatly appreciated. To donate, go to KU Endowment: Give to KU - Haslam Formulation Education & Research
• For those who wish to participate, but cannot attend in-person, please contact Michelle Huslig at mrhuslig@ku.edu after you complete registration for Zoom meeting details.

Tentative Schedule

Receiving Course Credit

Anyone interested in receiving course credit for attending this formulation series should enroll in PHCH 850 “Pharmaceutical Materials Science: Application to the Development of Pharmaceutical Solids” for the Summer 2023 semester. IMPORTANT: Tuition charges will apply.

Non-Degree Seekers

KU Post-Docs, KU Researchers, and Industrial Affiliates interested in receiving non-degree seeking course credit must apply for "non-degree seeking" admissions.

What is the advantage of actually enrolling, instead of just registering, in the Special Topics Series as a KU Course?

1. It will appear on your transcript as part of a permanent record --- PHCH 850 “Pharmaceutical Materials Science: Application to the Development of Pharmaceutical Solids”
2. It will be pass/fail, pass if you attend and participate in the “Fun Work” at, and for, the Thursday and Friday 1:30 - 3:00 sessions; fail if you don’t…but then don’t sign up.
3. You will have fun putting into action what you are learning. The class will be split into two groups and you will be assigned either a weak base or weak acid drug to develop a manufacturable and marketable formulation. An example of the type of information you will receive is in the two attachments along with a third attachment which will help to guide your thinking. You will also be provided an excel calculator called eTab, which is a tool that models the mechanical properties of solid mixtures, given that you have the measured or estimated physicomechanical properties of the drug and various excipients. Greg has also prepared a short (10 min) video which you can use as a guide for the use eTab, although much of it is self-explanatory.
4. You will have an appreciation not only of how complex making a solid dosage form which is manufacturable really is, but you will have a better sense of how to use principles of material sciences to guide rational scientific decisions. Although, you should get this from the presentation parts as well.
5. This will be an example of fun learning activity that will probably carry with you wherever you might end up!!
6. A brief look at the top 300 prescribed drugs, greater than 90-95% are oral dosage forms. For info about the top 300 prescribe drugs, see Top 300 of 2020 (ClinCalc).

About John L. Haslam

Colleagues described John as a hands-on, tireless inquisitor whose curiosity led to all kinds of formulations and drug delivery systems and devices as well the ability to make and modify the equipment necessary to analyze the performance of these dosage forms and systems. His contributions to young scientists, as he patiently worked with graduate students in the Department of Pharmaceutical Chemistry, was exemplary of the giving person that he was.