Prince Of Spray Drying Returns As Earl Of Dispersion
By Louis Garguilo, Chief Editor, Outsourced Pharma
Tim Scott traces the arc of spray drying from its advent to today's advanced amorphous dispersion technology.
He was co-founder, and president of Pharmatek Laboratories from 1999 until 2016, when he sold the company – a leader in spray-drying knowhow and services – to Catalent.
After Pharmatek, Scott tried his hand at drug discovery, spinning technologies out of his alma mater UC San Diego, including Tega Therapeutics, where he served as president & CEO.
At the same time, DisperSol has changed its name to AustinPx, Pharmaceutics and Manufacturing, to reflect its new direction as a CDMO – with Scott as as president and CEO.
For the first five years of DisperSol's existence, it developed, patented, and focused on selling technology and instrumentation to improve drug bioavailability in poorly soluble molecules, by rendering drugs amorphous.
During the company's second five-year period, it pivoted to progressing two candidates enabled by its proprietary technology into clinical study. Those currently late-stage programs will be licensed out as the focus turns to providing pharmaceutical-chemistry services centered on AustinPx's amorphous dispersion prowess.
"The name AustinPx represents where we come from; the original technology was developed and spun out of University of Texas at Austin," explains Scott.
"Px stands for ‘pharmaceutics.' To our core, we are a pharmaceutics company. Our formulation strategy for each drug is based on the unique physiochemistry of that compound. We have next-generation technology for rendering poorly soluble active pharmaceutical ingredients amorphous."
Scott joined AustinPx after receiving a call last year from Research Corporation Technologies, the main investor in DisperSol. "I loved the technology, and enjoyed meeting the management team. The technology, called KinetiSol, is a new way of creating amorphous dispersions. The industry started with spray drying, and after hot-melt extrusion, in my opinion this is next generation amorphous dispersion."
Scott had originally suggested he join the board, but says "they were eager to flip this technology into a service model and also sell the instrumentation to others. I thought, ‘I've still got some gas in the tank, I'd really enjoy doing this.'"
Below, Scott tells us how he got started and plans to proceed, and provides an important revisitation on the challenges of poor solubility and small-molecule development. In part two, we'll learn how a drug developer changes skin from sponsor to CDMO.
Roots And Shoots
As mentioned above, the technology originated at UT Austin, specifically in the labs of Bill Williams and Jim McGinnity, "two people who have spent their careers developing technologies for improving drug delivery," says Scott. Two of their graduate students repurposed a plastics-recycling technology for pharmaceutical applications – they are DisperSol's founders Chris Brough and Dave Miller, who are still with AustinPx as CTO and CSO, respectively.
Their initial focus changed to developing their own products to demonstrate proof of concept, derisk the regulatory process, and demonstrate the technology worked at commercial scale.
"When I came in," says Scott, "my first thought was this is the natural progression of amorphous dispersion. But the problem was they'd only developed five or six products in the last five years. One way to increase the real value was to greatly increase that number. You could do that by providing the technology and knowhow as a service to the industry, and sell the instruments as well."
The goal, says Scott, is one-hundred molecules over the next three years moving towards the clinic.
"I think that's reasonable based on the high percentage of poorly soluble compounds coming out of discovery, the large number of spray-dried candidates in the clinic, and the thirty or so approved drugs on the market," he says.
The Spray Of The Land
According to a review in ScienceDirect, some 40% of all marketed drugs, and a whopping 90% in the R&D pipeline, are poorly water-soluble. Thus, says Scott, "Spray drying today is incredibly popular," and he believes improved and reliable spray drying by CDMOs and other manufacturers is and has been benefitting – and altering – the way drug discovery and development is approached.
However, while spray drying is an enabling technology, there are major challenges. One of those is the organic solvents and nitrogen used in the process. Large CDMOs that spray dry for their clients regularly use thousands of liters of organic solvents and countless tanks of nitrogen, says Scott.
Obviously, that's not good for the environment, and Scott has already had conversations with pharma companies that don't like the current situation. What they do like is that AustinPx's amorphous dispersion process uses "zero organic solvents, and no nitrogen."
Also needed in current spray-drying processes are certain polymers mixed with the drug substance. Basically, there are three polymers that work well with the organic solvents. A polymer is mixed with the drug substance, which separates when dry – breaks the crystalline structure of the drug – so it's more soluble and therefore more bioavailable.
Scott says the advanced amorphous dispersion system his company utilizes has 20 some polymers that can be used, plus other excipients and lubricants to expand development opportunities.
This all works when materials are run through a KinetiSol – a fusion-based kinetic-mixing instrument with both sheer and blending forces. This instrument (with a relatively small footprint compared to other spray-drying equipment) creates a molten polymer that solubilizes the drug, rendering it amorphous, according to Scott. Other elements, including cyclodextrins [sugar molecules bound together in rings of various sizes], and lubricants enhancing flow can also be introduced to help improve product flow.
Looking more broadly, Scott reenters the service sector at a time when the (misnamed) Inflation Reduction Act (IRA), passed by the U.S. Congress, includes a provision providing the government certain powers to regulate the price of drugs, and subjects small molecules to price regulation after just nine years of exclusivity.
"The IRA can reduce incentives for small-molecule development," says Scott. "The calculus for drug developers has changed."
And that new calculus may well include a look at new technologies to help extend drug exclusivity. Scott thinks he's back in the industry sector with one such technology. Getting it into the hands of developers is his goal.
First, though, he must turn an erstwhile drug-developer into a competent CDMO. We'll cover that next.