Higher-impact drugs with fewer doses

 

Vivian Bi, Ashland technical director, discovers unique solutions to drug solubility challenges [tweet this]

 

Sixty-four million Americans – one out of every five people – take at least five different prescription medications a day. Odds are, they’re taking some of them more than once.

What if one dose of a medication was 18 capsules or tablets?

That’s the problem a pharmaceutical company brought to Dr. Vivian Bi, technical director, Contract Research and Solubilization, and her colleagues at the Ashland Specialty Ingredients lab in Wilmington, Del.

“We didn’t like the formulation they had,” says Bi. “It was almost like food; it wasn’t like a drug any more. Eighteen capsules?”

The challenge is widespread
That is the problem with 90 percent of the medications under development today – they are poorly soluble, meaning it’s more difficult for the active ingredient to dissolve and enter the bloodstream. That means it takes more tablets or capsules to deliver the correct dosage. Eighteen, however, would be on the extreme end of the spectrum.

“The customer wasn’t confident we could develop a new formulation in time for the next clinical trial, which was only four months away,” recalls Bi. “We worked very hard and within four months had developed one pill that doubled the exposure of the drug compared to 18 capsules.

“If you think about the patient, that’s a very meaningful impact,” she adds.

Differing medication compounds can make each set of solubility issues a bit different as well, so there is no single solution to the problem. Bi recalls one drug which had to deliver a high dose-per-tablet. Another had a structure that tended to stay crystallized, inhibiting absorption. The challenge for researchers is determining which polymer – or combination of polymers – will effectively combine with the active ingredients to deliver solubility impact without producing undesirable side effects.

“You think of scientists as having a very strong academic background, meaning they know the science behind the technology,” says Dr. Stuart Porter, senior research fellow and technical lead, Ashland Specialty Ingredients. “That’s true for Vivian, but she goes far beyond that. She has broad expertise because of her career in the pharmaceutical industry before joining Ashland. She can explore the full possibility of our polymers and how they can be adapted to solubility solutions.”

Broad experience on a big stage
Prior to joining Ashland in 2011, Bi worked in research and development, focusing on formulation, for three major pharmaceutical companies. That experience and knowledge was invaluable when she was faced with especially pesky drug candidates. For one extremely poorly soluble compound, she incorporated cross-linked povidone into water-soluble polymers. The water-soluble polymer enhanced dissolution and the cross-linked povidone helped with keeping the active ingredient stable.

“It was kind of like creating a solid wall around the active ingredient to stop the molecules from moving around,” she recalls. “It kept the molecules from realigning themselves and turning into a crystalline material.”

The solution was unique enough that a patent application has been filed.

“We’ve had a number of customers comment on the breakthrough work she has done,
says Deneen Law, director, Global Marketing and Innovation, Pharmaceutical and Nutrition, Ashland Specialty Ingredients. “Vivian understands both the polymers and the chemistry, as well as the final formulation. She has actually been in the position of our customers and I think that’s what sets her apart when it comes to being a solutions provider.

“She has helped customers more quickly develop formulations, reduce the costs of screening formulations and select the right process for solubility,” Law adds.

Going far outside of the box
Bi credits unconventional thinking with igniting her innovative skills.

“I have crazy ideas all the time in daily life and also at work. For example, I would think about some equipment to help me wrap gifts for my children when they were young,” she says. “I would think about what could keep their heads up straight in the car when they fell asleep so they would not get uncomfortable.

“Sometimes in the lab, the typical technology does not work. Being a formulator myself, I try to be playful or entertain different ideas. Typically people will give up and say, ‘OK, there is no good polymer that will be suitable.’ I like to use combinations to help us to achieve complicated goals,” she says.

Bi’s sometimes non-traditional approaches have enhanced the company’s reputation,
says Porter.

“She has expanded our capabilities,” he says. “We’re a company that can do things a little differently. I think that speaks well of us if you have a problem and are looking for a solution.

“She is a consummate team player. You know you can always count on her to provide insight and suggestions in a way that helps you solve problems and move forward. Every time I’ve gone to her and said, ‘How can we adapt what you know to what I’m trying to do?’ She is extremely willing to do that,” he adds.

Law agrees that the breadth of knowledge, experience and teamwork sets Bi apart.

Finding the way to the best result
“Bioavailability enhancement (increasing the amount of drug that enters circulation with an active effect) is a significant need of most of our customers. Vivian has been able to offer our customers and Ashland a wealth of knowledge, helping to access and screen polymers to find the best solubilizer,” she says. “She is truly an expert in solid dispersion and solubility technologies.”

To Bi, it’s a matter of looking forward to finding the answers.

“After I got into the industry, I was lucky enough to touch every single aspect of pharmaceutical development,” she says. “All the way from drug discovery to pre-formulation to clinical studies and research. Typically, people work in one area for a very long time…I’m focused, yet still have a broad range.

“I like to think positively…about what we can do to make a situation better…We consider ourselves a solutions destination,” she adds. “I’ll hear or see the ‘ah-ha’ moment from the customer and that certainly makes me happy.”

Meet Vivian Bi

Medicines are better today because Vivian Bi decided not to go to medical school.

“When I was young, I always wanted to be a medical doctor and in high school I was invited to visit a medical school,” she recalls. But after seeing dissected cadavers in an anatomy lab, she decided it wasn’t for her.

“But I still had an interest in the human body, so I thought, ‘OK, pharmacy is a close relative,’” she says. “I chose industrial pharmaceutics. After I got into the formulation area, I really started to love to use the equipment to see the outcome.”

She grew up in Chengde, in Heibe province in northern China. “It is cold; very, very cold,” she says. She spent a lot of time with her grandmother, who lived nearby.

“I had a very happy childhood. There was a small river and I would go with the neighborhood children and catch small fish and frogs. Those are things that will stay forever in my memory.”

Richard, Brianna, James and Vivian

She and her husband, James, a software engineer, have a son, Richard, 18, and daughter, Brianna, 8.

She loves to garden and dreams of being a landscaper after she retires. She learned to ski after a college professor “almost pushed me into a club, and it became a long-lasting hobby.”

She is particularly fond of the movie version of “The Sound of Music.”

“I don’t remember how many times I have watched it, by myself and with my daughter,” she says. “I can sing most of the songs and I love Maria, the positive way she sees the world and how much she can influence other people.”

Classical music is a passion, especially with her son playing violin and her daughter learning piano. Johan Bach, Antonio Vivaldi and Friedrich Burgmüller are on the playlist.

As Maria sang in the movie, those are a few of her favorite things.

At her son Richard's high school graduation

Education

  • Bachelor of Science, engineering, Shenyang Pharmaceutical University, China.
  • Doctorate in pharmaceutical science, Meijo University, Japan.

Selected patents and publications

  • Highly loaded amorphous efavirenz composition and process for preparing the same, with M.A. Rahman, J.D. Lester, T. Durig and R. Bull, U.S. Patent No. 9,114,170, Aug. 25, 2015.
  • “The Effects of Screw Configuration and Polymeric Carriers on Hot Melt Extruded Taste Masked Formulations Incorporated into Orally Disintegrating Tablets,” with J.T. Morott, M. Pimparade, J.B. Park, et. al., Journal of Pharmaceutical Sciences,  2015.
  • “Investigation of the Interactions of Enteric and Hydrophilic Polymers to Enhance Dissolution of Griseofulvin Following Hot-Melt Extrusion Processing,” with R.C. Bennett, J.M. Keen, S. Porter, et. al., Journal of Pharmacy and Pharmacology, 2015.
  • “Formation Mechanism of Wet-Compressed Fast Disintegrating Tablets Containing a Poorly Water-Soluble Model Drug,” Journal of of Drug Delivery Science and Technology, 2006.
  • “A Comparative Study on the Metastable Equilibrium Solubility Behavior of High-Crystallinity Carbonated Apatites Using pH and Solution Strontium as Independent Variables,” Journal of Colloied and Interfacial Science, 2005.

Selected awards

  • Academic Achievement Award, Sixth Pharmaceutical Life Cycle Management Symposium, Japan, 2012.
  • Pharmaceutical and Analytical Development Innovation Award, AstraZeneca, 2009.
  • Speed and Quality Challenge Award, AstraZeneca, 2007.

Memberships

  • Steering Committee, Lipid-Based Drug Delivery Systems Focus Group, American Academy of Pharmaceutical Scientists.
  • Controlled Release Society.

Traveling with her family