The invisible science behind every puff that revolutionized inhalation drug delivery
When you press down on an asthma inhaler and hear that familiar hiss, you're experiencing the culmination of decades of pharmaceutical innovation. Behind that life-saving puff stands the often-invisible work of scientists like Dr. Paul B. Myrdal, whose pioneering research in inhalation drug development and solubility prediction touched countless lives through improved medical treatments 1 . His career spanned industry and academia, resulting in developments that helped make inhalers more effective, reliable, and accessible 1 .
This is the story of how a curious scientist from Wisconsin revolutionized the way we deliver medicine to the human body—one microscopic particle at a time.
Developed groundbreaking models for predicting drug solubility that transformed pharmaceutical development.
Contributed to the world's first CFC-free steroid MDI, earning 3M's Technical Circle of Excellence award.
Paul Myrdal's path to scientific prominence began at the University of Wisconsin Madison, where his future in sciences was set in motion. A pivotal moment came when he met his future wife, Kelly Jo Koch, in freshman chemistry class. When Kelly transferred to the University of Arizona to complete her PharmD, Paul followed, completing his BS in Molecular and Cellular Biology in 1989 1 .
1989 - 1995
Myrdal joined the laboratory of Dr. Samuel Yalkowsky, where his graduate work focused on the science of solubility and the application of physical chemical properties to calculate aqueous solubility. These early investigations led to seminal publications on two important systems: the Unified Physical Property Estimation Relationships (UPPER) and the Aqueous Functional Group Activity Coefficients (AQUAFAC) 1 .
1995 - 2000
Dr. Myrdal brought his expertise to Minnesota Mining and Manufacturing Company (3M), where he spent five years working on the preformulation and development of multiple different HFA-based metered dose inhaler programs 1 . His work included formulation development, manufacturing process scale-up, and solid-state characterization of different drug substances 1 .
At 3M, Myrdal contributed to developing the manufacturing process for the world's first CFC-free steroid MDI, Qvar® (beclomethasone dipropionate HFA inhalation aerosol). This innovation earned him 3M's coveted Technical Circle of Excellence award in 1998 1 .
2000 - 2018
Myrdal returned to the University of Arizona College of Pharmacy as an Assistant Professor, where he spent the next 18 years building a respected research program focused on inhalation formulation development 1 . During his academic career, he directly supervised 8 Ph.D. students and served on the graduate committees of more than 15 Ph.D. graduates 1 .
At the heart of many of Myrdal's contributions was the complex challenge of solubility prediction—accurately forecasting how and to what extent a drug compound will dissolve in different media. This work is fundamental to pharmaceutical development because a drug's effectiveness often depends on how readily it dissolves and becomes available to the body 1 .
Aqueous Functional Group Activity Coefficients - estimated aqueous solubility based on molecular structure 1 .
Unified Physical Property Estimation Relationships - calculated physical properties of chemical compounds 1 .
Myrdal's early work on AQUAFAC and UPPER provided researchers with practical tools to estimate aqueous solubility based on a compound's molecular structure 1 . These systems allowed scientists to predict solubility without conducting time-consuming laboratory tests for every compound.
Screen potential drug candidates more efficiently in early development stages
Understand the contribution of different functional groups to overall solubility
Predict solubility without time-consuming laboratory tests for every compound
| Contribution | Description | Significance |
|---|---|---|
| AQUAFAC | Aqueous Functional Group Activity Coefficients | Estimated aqueous solubility based on molecular structure |
| UPPER | Unified Physical Property Estimation Relationships | Calculated physical properties of chemical compounds |
| Qvar® Development | First CFC-free steroid metered dose inhaler | Eliminated ozone-depleting propellants from medical inhalers |
| Novel Solubility Measurement | Method for determining solubility in HFA propellants | Enabled accurate formulation of inhalation medicines |
One of Myrdal's most innovative contributions came from addressing a fundamental problem in inhalation drug development: how to accurately measure the solubility of drug compounds in HFA propellants. These measurements were notoriously difficult because HFA propellants are volatile and require specialized high-pressure equipment to handle. Without reliable solubility data, formulators struggled to create consistent, effective inhalers 1 .
HFA propellants are volatile and require specialized high-pressure equipment, making solubility measurements extremely challenging.
In 2004, Dr. Myrdal and his student Amit Gupta published a novel method for determining solubility in aerosol propellants that addressed these challenges 1 . Their approach involved:
Creating a calibrated chamber capable of containing HFA propellants under pressure
Developing a sampling system that could withdraw precise samples without losing propellant
Using HPLC (High-Performance Liquid Chromatography) to analyze dissolved drug concentration
Establishing temperature control to study solubility across different environmental conditions
The method provided reliable, reproducible solubility measurements for various drug compounds in HFA propellants. This data proved crucial for:
This methodological breakthrough removed a significant bottleneck in inhalation product development and represented the kind of practical innovation that characterized much of Myrdal's career—solving everyday problems with sophisticated science.
| Research Focus | Key Finding | Application |
|---|---|---|
| Solubility Prediction | Developed AQUAFAC models for estimating aqueous solubility | Early-stage drug candidate screening |
| Propellant Solubility | Created reliable method for measuring drug solubility in HFA propellants | Formulation of metered-dose inhalers |
| Ethanol Cosolvent | Balanced ethanol concentration with product performance in HFA systems | Optimized spray characteristics and drug delivery |
| Lung Cancer Therapies | Investigated 5-lipoxygenase inhibitors delivered via inhalation | Potential new treatment avenues for lung cancer |
The field of inhalation drug development relies on specialized materials and methods. Myrdal's work exemplified the interdisciplinary nature of this research, which combines elements of chemistry, physics, engineering, and biology. Below are key components from the inhalation scientist's toolkit that featured prominently in Myrdal's research:
| Tool/Material | Function | Example in Myrdal's Work |
|---|---|---|
| HFA Propellants | Environmentally-friendly propellant replacing CFCs | Development of Qvar® and other HFA-based inhalers |
| Ethanol Cosolvent | Enhances drug solubility in propellant systems | Optimized concentration for product performance |
| 5-Lipoxygenase Inhibitors | Potential therapeutic compounds for lung conditions | Investigated for lung cancer prevention in animal models |
| Novel Excipients | Inactive substances that enhance drug delivery | Developed biocompatible excipients for HFA MDIs |
| AQUAFAC Models | Computational prediction of solubility | Estimated aqueous solubility of new drug candidates |
| Metered Dose Inhaler Hardware | Physical device components | Studied effects on aerosol size distributions |
Environmentally-friendly alternative to ozone-depleting CFCs
Enhanced drug solubility in propellant systems
Potential therapeutic compounds for lung conditions
Dr. Paul Myrdal passed away on May 19, 2018, but his scientific legacy continues through the inhalation technologies he helped develop and the scientists he mentored 1 . Throughout his career, he published over 50 peer-reviewed manuscripts, served on editorial boards, and was co-inventor on multiple patents 1 .
Directly supervised 8 Ph.D. students and served on committees for more than 15 Ph.D. graduates, influencing the next generation of pharmaceutical scientists.
Authored over 50 peer-reviewed manuscripts that continue to be cited by researchers in pharmaceutical science and inhalation technology.
Perhaps less visible but equally important was Myrdal's dedication to mentoring students and colleagues. Those who worked with him remembered his ability to "make a colleague or student pause and reconsider their conclusion or data" and his willingness "to always have time to discuss a question (about science or life) over a beer at a conference" 1 .
This combination of scientific excellence and personal mentorship created a legacy that extends far beyond his publications and patents. As noted in his memorial, "It is through these valuable contributions to science and the careers of so many peers that Paul's legacy will be remembered for years to come" 1 .