Lynn Melling, Contributing Author04.19.17
In 1995, Charlie Thiel, a former chemist at 3M Drug Delivery Systems, met an elderly Australian physician who suffered from asthma. “He gave me a hug and told me, ‘Charlie, if it wasn’t for your invention, I would be dead.’ For Thiel, it was the most important moment of a 46-year career that revolutionized inhalation drug delivery.
In 1956, Charlie Thiel was a chemist on a small team at Riker Laboratories (now 3M Drug Delivery Systems) that invented and developed the first pressurized metered-dose inhalers. The path to this discovery began in April of 1955 with a seemingly innocent question from a 13-year-old girl with asthma. She had grown frustrated with using a squeeze bulb glass nebulizer, which was easily broken and not very effective. “The13-year-old Susie Maison asked her father why they couldn’t put her asthma medication in a spray can, like they do hairspray,” Thiel says. “Her father said, ‘Why not?’” Her father was Dr. George Maison, president of Riker Laboratories.
At the time, Riker was a subsidiary of the Rexall Drug Company, which produced hairspray among other things. Maison asked his head chemist, Irv Porush, to answer Susie’s question. Using suggestions from the hairspray lab down the hall, Porush got to work. Thiel recalls, “Irv had been a chemist for Coca-Cola bottling company, and he knew that those hourglass-shaped green glass bottles that Coke used to come in would hold 13-hundred pounds per square inch pressure. So, Irv bought a case of bottles and a bottle capper and some CFC refrigerants that were considered safe by the Underwriters Laboratory and set to work formulating a metered dose inhaler. In those pressure vessels, he made a formulation that was about 50 percent alcohol and the rest CFC propellant mix.”
Coincidentally, at that same time, metering valves, invented by Philip Meshberg, and small plastic coated aerosol vials had just become available. They were intended primarily for use in perfume bottles. “Irv adapted the metered dose valve and the coated glass vial and put his formulation in it. Then they had a plastics company design a mouthpiece for it,” Thiel says.
Safety tests were conducted in June of 1955 and in March of 1956, the FDA approved the drug applications for what are now known as rescue inhalers. “The product was launched before the end of the month―the whole works, in less than a year,” Thiel says. “The timeline is incredible,” says Steve Stein, lead inhalation research specialist at 3M. Stein has extensive experience in the regulatory process of the inhalation drug delivery industry and says that pace would be unthinkable today. “Nowadays, that process would take close to a decade,” Stein says.
The success of the new delivery system for asthma inhalers led to a desire to apply the technology to other applications such as nasal rhinitis. This, however, was plagued by one big problem. “Here’s where the alcohol comes in. It stings like crazy in your nose,” says Thiel. The team needed to figure out how to get the medicine from inside the MDI canister to inside the patient in a safe, tolerable and effective way. That is when Thiel entered the picture. He had no idea he was about to begin a painstaking process of designing what would become an innovative suspension of the medication in a liquefied gas propellant that would not only dramatically improve the efficiency of this emerging technology, but would literally change millions of lives.
“In June 1956, I was asked to help out as a pair of hands to develop a nasal decongestant spray,” he says. “I had some experience with emulsions but not with making aerosols. I decided, I’ll just dissolve the drug in water and then make an emulsion of the drug in the liquefied gas propellants.”
It didn’t work. So he kept trying, testing out various combinations on himself and his colleagues. “It was a lot of fun. We tried everything on ourselves in those days,” Thiel says. “Some would discharge a foam like shaving cream. Some would sting with a spray. But the weirdest of all, some of the emulsion formulations that I made would result in droplets depositing in the nasal passage that still contained some of the propellant. With that stuff in your nose, holding on to the propellant as it warmed up, bubbles would form in your nose and you had a frying sensation. Believe me, it was a crazy sensation.”
After 114 failed experiments, Thiel was given a new assignment. “Someone in the clinical department wondered if I could put the drug hydrocortisone in my formulation so that it could be used for asthma. The hydrocortisone didn’t dissolve in either the propellant or the water, but it made a decent emulsion-suspension. But when that was sprayed out, it was just too wet to be inhaled. The droplets were too large.” Thiel says.
Then finally, he made a breakthrough. Thiel recalls, “I just happened to look at the label on the bottle of hydrocortisone and it said ‘microfine’. If I can make a suspension, would the powder disperse in the liquefied propellant?’ But it would need a surfactant to disperse the tiny drug particles. I tried one of my surfactants. A surfactant is like a detergent thing that kept the emulsions together,” Thiel says. “The first thing that I tried worked! It made a good suspension when it was in the formulation, and then when you fired it from the mouthpiece, a beautiful, dry fog came out.”
The discovery was profound. “It increased the amount of drug that was delivered to the lung dramatically,” says Steve Stein. “In some of the early studies of the inhalers, doctors would take patients who weren’t really being helped by any other available therapies and they then would have them try the metered-dose inhaler. The vast majority of them were significantly helped,” Stein says. “These were the hardest to help patients. That shows how important a breakthrough it was.”
Today, the metered-dose inhaler is still widely used. “When you think of the modern pharmaceutical aerosol industry, I think the work Charlie and the other scientists at Riker did really started it,” Stein says. “It was the first convenient, portable, user-friendly system available. According to IMS data in 2014, more than 2,000 people are taking doses from a metered-dose inhaler every second.” While it is impossible to estimate how many lives have been saved, Thiel is humbled by the thought of saving just one.
Thiel says there is still much room for improvement when it comes to inhalation drug delivery. He says many patients still have difficulty synchronizing their inhalation with the discharge of the inhaler, so they don’t receive the proper dose. He adds, many healthcare professionals haven’t received proper training in how patients should use them. Thiel says, “My wife had bronchitis and was prescribed a rescue inhaler. The pharmacist tried to show Carol how to use it. I think a person might get more drug in their left ear than in their lungs.”
Thiel and Stein say such problems are being addressed and innovation continues. For instance, the 3M Intelligent Control Inhaler is being developed to visually instruct patients how to use it and ensures they receive the proper dose. The 3M Intelligent Control Inhaler is an example of future inhalers that will be capable of linkingto mobile devices. “I think it’s important that these solutions will enable a patient to show their doctor how well they are using their metered-dose inhaler,” Thiel says.
Thiel retired in 2000, after 46 years in the field. He says, “working at a place like 3M, I was never bored and had the creative freedom to try new things.” Thiel continues, “People asked me, ‘Why did you stay so long?’ I said, ‘It was hard to leave. 3M provided a beautiful laboratory and paid me to play in it.’”
Charlie Thiel
Coca-Cola and Coke are registered trademarks of the Coca-Cola Company © 2017
3M is a trademark of the 3M Company © 2017
In 1956, Charlie Thiel was a chemist on a small team at Riker Laboratories (now 3M Drug Delivery Systems) that invented and developed the first pressurized metered-dose inhalers. The path to this discovery began in April of 1955 with a seemingly innocent question from a 13-year-old girl with asthma. She had grown frustrated with using a squeeze bulb glass nebulizer, which was easily broken and not very effective. “The13-year-old Susie Maison asked her father why they couldn’t put her asthma medication in a spray can, like they do hairspray,” Thiel says. “Her father said, ‘Why not?’” Her father was Dr. George Maison, president of Riker Laboratories.
At the time, Riker was a subsidiary of the Rexall Drug Company, which produced hairspray among other things. Maison asked his head chemist, Irv Porush, to answer Susie’s question. Using suggestions from the hairspray lab down the hall, Porush got to work. Thiel recalls, “Irv had been a chemist for Coca-Cola bottling company, and he knew that those hourglass-shaped green glass bottles that Coke used to come in would hold 13-hundred pounds per square inch pressure. So, Irv bought a case of bottles and a bottle capper and some CFC refrigerants that were considered safe by the Underwriters Laboratory and set to work formulating a metered dose inhaler. In those pressure vessels, he made a formulation that was about 50 percent alcohol and the rest CFC propellant mix.”
Coincidentally, at that same time, metering valves, invented by Philip Meshberg, and small plastic coated aerosol vials had just become available. They were intended primarily for use in perfume bottles. “Irv adapted the metered dose valve and the coated glass vial and put his formulation in it. Then they had a plastics company design a mouthpiece for it,” Thiel says.
Safety tests were conducted in June of 1955 and in March of 1956, the FDA approved the drug applications for what are now known as rescue inhalers. “The product was launched before the end of the month―the whole works, in less than a year,” Thiel says. “The timeline is incredible,” says Steve Stein, lead inhalation research specialist at 3M. Stein has extensive experience in the regulatory process of the inhalation drug delivery industry and says that pace would be unthinkable today. “Nowadays, that process would take close to a decade,” Stein says.
The success of the new delivery system for asthma inhalers led to a desire to apply the technology to other applications such as nasal rhinitis. This, however, was plagued by one big problem. “Here’s where the alcohol comes in. It stings like crazy in your nose,” says Thiel. The team needed to figure out how to get the medicine from inside the MDI canister to inside the patient in a safe, tolerable and effective way. That is when Thiel entered the picture. He had no idea he was about to begin a painstaking process of designing what would become an innovative suspension of the medication in a liquefied gas propellant that would not only dramatically improve the efficiency of this emerging technology, but would literally change millions of lives.
“In June 1956, I was asked to help out as a pair of hands to develop a nasal decongestant spray,” he says. “I had some experience with emulsions but not with making aerosols. I decided, I’ll just dissolve the drug in water and then make an emulsion of the drug in the liquefied gas propellants.”
It didn’t work. So he kept trying, testing out various combinations on himself and his colleagues. “It was a lot of fun. We tried everything on ourselves in those days,” Thiel says. “Some would discharge a foam like shaving cream. Some would sting with a spray. But the weirdest of all, some of the emulsion formulations that I made would result in droplets depositing in the nasal passage that still contained some of the propellant. With that stuff in your nose, holding on to the propellant as it warmed up, bubbles would form in your nose and you had a frying sensation. Believe me, it was a crazy sensation.”
After 114 failed experiments, Thiel was given a new assignment. “Someone in the clinical department wondered if I could put the drug hydrocortisone in my formulation so that it could be used for asthma. The hydrocortisone didn’t dissolve in either the propellant or the water, but it made a decent emulsion-suspension. But when that was sprayed out, it was just too wet to be inhaled. The droplets were too large.” Thiel says.
Then finally, he made a breakthrough. Thiel recalls, “I just happened to look at the label on the bottle of hydrocortisone and it said ‘microfine’. If I can make a suspension, would the powder disperse in the liquefied propellant?’ But it would need a surfactant to disperse the tiny drug particles. I tried one of my surfactants. A surfactant is like a detergent thing that kept the emulsions together,” Thiel says. “The first thing that I tried worked! It made a good suspension when it was in the formulation, and then when you fired it from the mouthpiece, a beautiful, dry fog came out.”
The discovery was profound. “It increased the amount of drug that was delivered to the lung dramatically,” says Steve Stein. “In some of the early studies of the inhalers, doctors would take patients who weren’t really being helped by any other available therapies and they then would have them try the metered-dose inhaler. The vast majority of them were significantly helped,” Stein says. “These were the hardest to help patients. That shows how important a breakthrough it was.”
Today, the metered-dose inhaler is still widely used. “When you think of the modern pharmaceutical aerosol industry, I think the work Charlie and the other scientists at Riker did really started it,” Stein says. “It was the first convenient, portable, user-friendly system available. According to IMS data in 2014, more than 2,000 people are taking doses from a metered-dose inhaler every second.” While it is impossible to estimate how many lives have been saved, Thiel is humbled by the thought of saving just one.
Thiel says there is still much room for improvement when it comes to inhalation drug delivery. He says many patients still have difficulty synchronizing their inhalation with the discharge of the inhaler, so they don’t receive the proper dose. He adds, many healthcare professionals haven’t received proper training in how patients should use them. Thiel says, “My wife had bronchitis and was prescribed a rescue inhaler. The pharmacist tried to show Carol how to use it. I think a person might get more drug in their left ear than in their lungs.”
Thiel and Stein say such problems are being addressed and innovation continues. For instance, the 3M Intelligent Control Inhaler is being developed to visually instruct patients how to use it and ensures they receive the proper dose. The 3M Intelligent Control Inhaler is an example of future inhalers that will be capable of linkingto mobile devices. “I think it’s important that these solutions will enable a patient to show their doctor how well they are using their metered-dose inhaler,” Thiel says.
Thiel retired in 2000, after 46 years in the field. He says, “working at a place like 3M, I was never bored and had the creative freedom to try new things.” Thiel continues, “People asked me, ‘Why did you stay so long?’ I said, ‘It was hard to leave. 3M provided a beautiful laboratory and paid me to play in it.’”
Charlie Thiel
Coca-Cola and Coke are registered trademarks of the Coca-Cola Company © 2017
3M is a trademark of the 3M Company © 2017
