Micronization has become an essential tool for overcoming the solubility challenges that dominate today’s small molecule drug pipelines, with more than 90% of new compounds exhibiting poor solubility. As molecules become increasingly complex and potent, the demand for specialized particle size reduction techniques and containment solutions has grown. Microsize, one of only two dedicated micronization specialists in the United States, brings over 30 years of expertise, cutting-edge capabilities, and a commitment to high-touch service. With one of the largest dedicated facilities globally and proprietary jet milling technology, Microsize offers unmatched scalability and technical insight. In this Q&A with Pharma’s Almanac Editor-in-Chief David Alvaro, Ph.D., TJ Higley, CEO of Microsize, discusses evolving industry needs, the company’s unique capabilities, and the future of micronization in pharmaceutical development.
David Alvaro (DA): To begin, can you introduce us to Microsize and explain some of the long history underpinning the current business?
TJ Higley (TJH): Microsize specializes in particle size reduction — we’re one of only two specialists in the United States providing this service. We’ve been in this space for 30 years, evolving through different ownership structures and becoming a world leader in terms of our experience, breadth of capabilities, and service expertise.
The company was originally established as Powdersize in 1994, and we operated under that name for 20 years. I was part of that journey, and we eventually sold the company to Capsugel, which was later acquired by Lonza. Over time, we transitioned from a small, private company with just a few employees in the early 1990s to a mid-sized business with around 40 employees when it was acquired. That experience gave us insight into operating within a large global pharmaceutical company, from quality and regulatory standards to operational and HR processes.
When we spun the business back out as Microsize in 2022, we took all that expertise and returned to being a privately held company. The biggest advantage of this transition is that we regained the high-touch, personalized service that can sometimes get lost in a large corporate structure. Instead of needing a project of a certain size to get attention, our clients now work directly with our team and subject matter experts, making the process much more hands-on and collaborative.
What sets us apart in this field is our depth of experience and the scale of our operations. We have one of the largest facilities in the world dedicated to this work, with 100,000 square feet of manufacturing space and 14 suites. We’re also one of the only companies globally that designs and builds its own jet mills and jet milling equipment. That means we don’t just provide micronization as a service — we also have uniquely deep technical expertise in the equipment itself, which allows us to optimize every aspect of the process, from gram-level DOE trials to metric ton process validations.
Another key differentiator is that we don’t just work with small molecule APIs (active pharmaceutical ingredients), although that remains the bulk of our business. We also micronize functional excipients like colorants, compressants, lubricants, and disintegrants — essentially every layer of a tablet formulation. Over the years, we’ve worked with everything from highly crosslinked large molecules that are difficult to grind to extremely slippery lubricants and the diverse polymer types in betweeen with unique physical properties. That experience has given us unmatched expertise in how to handle different materials — how best to feed, mill, and collect them — making us one of the most versatile players in the industry.
DA: How have you seen the demand for micronization change over the years?
TJH: The biggest shift has been in the nature of small molecules themselves. When I first started, only about 20% of small molecules faced solubility challenges. Today, that number is above 90% and approaching 100%. That increase has driven a significant rise in demand for micronization services over the years.
Small molecules have become more complex. They’re getting larger in molecular weight, which directly contributes to solubility challenges. As molecular complexity increases, so does the need for specialized particle engineering requirements.
Another major shift involves potency. More molecules today are highly targeted and highly potent, which means that their milling process needs to be contained for safety. Open-air milling is becoming less common fornew chemical entities (NCEs), while investment in specialized containment capabilities is growing. We’ve adapted to this shift by offering high-potency milling at both small and large scales in both development and GMP settings. We recently commercialized an OEB4 high-potency API and now process metric tons of high-potency compounds per year. Since we already have the capital investment and infrastructure in place, outsourcing to a specialist like us becomes an obvious choice for companies working with these types of molecules.
The third key trend is the growing need for more comprehensive analytical characterization. Particle size alone is no longer enough — understanding solid-state properties, morphology, and dissolution behavior is just as important. To meet this demand, we’ve expanded our capabilities to include solid-state analysis, scanning electron microscopy (SEM), and other advanced microscopy techniques.
We’ve also built an ecosystem around this with a partner called Solubility Company, which developed a proprietary technology called single-particle analysis (SPATM). This allows us to characterize solubility and dissolution in a novel way using only micrograms of API. It works in any screening environment desired — biorelevant buffer systems, different temperatures, pH ranges, and organic solvents — so we can assess solubility under virtually any condition, all in-house.
This technology also helps us optimize micronization from the start. Before we even begin the process, we can determine the intrinsic dissolution rate of a drug substance and predict the ideal particle size needed to achieve the best dissolution. Many companies have a target particle size in mind but don’t know what dissolution performance that size will yield. We take the guesswork out of it, reducing development time and trial iterations while ensuring that the final particle size meets the necessary specifications for a drug’s CMC (chemistry, manufacturing, and controls) package.
DA: Have the primary advancements in the past three decades been on the analytical side, or has there been significant innovation in milling technologies as well?
TJH: Micronization/milling technology has remained fundamentally the same since the 1970s. Jet mills, for example, have largely retained their core design. However, because we manufacture our own jet mills, we offer more flexibility than most service providers. Our range includes sizes from 1-inch all the way up to 30-inch mills, giving us broader capacity and the ability to tailor the milling process based on a material’s specific handling requirements.
That said, there has been some innovation in nanosizing technologies. One example is SoluMatrix, a dry powder nanosizing process developed within the last decade. It’s a novel milling approach, and we hold “right to use” licenses for it as part of our service offerings.
Still, when it comes to pharmaceutical applications, the primary milling methods remain hammer milling, pin milling, and jet milling — these continue to be the backbone of drug substance micronization.
DA: When customers come to Microsize, do they typically have a specific milling technology in mind, or are they more focused on the target particle size and performance attributes and leave the choice of technology up to you?
TJH: Most customers are agnostic about the specific milling technology — they’re primarily looking for the best way to enhance solubility. Because of that, we rarely use hammer milling, which is a coarser method. The real choice typically comes down to pin milling versus jet milling.
In most cases, the decision is based on the material’s characteristics and the required processing volume. Jet milling is a gentler process — it operates at ambient conditions and is highly efficient for throughput. Pin milling, on the other hand, generates heat and can be problematic for low-melting-point APIs or cohesive powders, as the tight tolerances between the rotor and stator can lead to blockages and material buildup.
If both methods can achieve the same particle size, we almost always recommend jet milling because it’s the more reliable and process-friendly option.
DA: You mentioned that one of the advantages of Microsize is that your smaller size gives you the ability to have a higher touch and more direct engagement with clients. But do you think that your experience as part of a larger organization before the spinout also given you more agility in terms of adapting to the needs of larger client companies?
TJH: Most clients come to us when they reach their first GMP need for early-phase clinical trial material. Once they’ve identified that they have a DCS (Developability Classification System) Class 2A compound with dissolution rate limitations, they typically recognize that micronization is the best solution. At that point, they engage with us to produce clinical trial material, explore different particle size ranges, and build out their CMC package.
This applies to both Big Pharma and smaller companies, but our seamless scalability makes us particularly attractive to large pharmaceutical companies. Because we have mills in every size range, clients don’t need to retransfer their process or revalidate when they scale up. That continuity streamlines development, reduces risk, and minimizes supply chain complexity.
That said, most of our inbound projects come from small to mid-sized pharma, simply because that’s where the majority of molecules originate. But we’re also an ideal partner for tech transfers of commercialized micronization processes. We operate some of the largest jet mills in the space and have the capacity to handle high-volume production. In many cases, we can offer faster turnaround times, higher throughput, and significant cost-of-goods (COGS) reductions compared with in-house operations or smaller providers. For companies looking to transfer an already-validated process, we provide a highly efficient, scalable solution.
DA: You mentioned that most customers begin working with you when they are first preparing for GMP. Is that ideal, or would there be benefits to earlier engagement?
TJH: In an ideal world, we’d love to engage with clients earlier, but there’s a hesitation. Many companies have their own small-scale jet mills for early-phase work and assume that handling it in-house is faster than outsourcing. It’s usually only when they scale up and realize their equipment isn’t sufficient — or when they need GMP compliance — that they look for a specialist like us. That’s the most common tipping point.
That said, with new analytical tools, there’s a strong case for involving us earlier. Through our partnership with Solubility Company, we can characterize solubility at the microgram level, allowing us to assess formulation strategies much earlier — during lead discovery when only milligram quantities of API are available. That means companies can make more informed decisions upfront about whether micronization is the right approach or if they need a more complex and costly alternative like spray drying or hot melt extrusion.
Even though early-stage engagement is valuable, our core business remains first-in-human GMP manufacturing. Beyond that, we also see significant opportunity in supporting companies as they scale to commercial volumes. Many organizations start with in-house development but later struggle with production demands as their program ramps up over four or five years. At that stage, we can step in, take on the commercial manufacturing, and free up their internal capacity so they can focus on their next pipeline projects.
DA: For a non-technical reader, what’s the best way to understand whether micronization is appropriate or if a program needs to pursue one of those amorphous solid dispersion approaches like hot melt extrusion or spray drying?
TJH: The best way to look at it is that the molecule itself dictates the right technology. There’s a classification system, and for a DCS Class 2A (low solubility, high permeability) molecule — where solubility is the primary issue — micronization is almost always the best choice. However, if a molecule falls into Class 3 (high solubility, low permeability) or 4 (low solubility, low permeability), other technologies, like spray drying or hot melt extrusion, may be more appropriate. In some cases, we can step outside of our core focus, but we prefer to stay in our lane and do what we do best — micronization. If a molecule requires it, we believe Microsize is the best partner to execute that process.
Where we really differentiate ourselves is in experience, scale, and capabilities. We’ve been in this space for 30 years, making us one of the most experienced providers in the United States. We also have significant scale — about 70% of our work is with commercial API production, so we’re built for seamless scalability from early development through commercialization. Another key advantage is that we manufacture our own jet mills, giving us greater flexibility, customization, and efficiency compared with companies relying on third-party equipment.
Additionally, we offer much more than just particle size reduction. We’ve integrated advanced characterization technologies, allowing us to assess not just particle size but also shape, solid-state properties, dissolution, and solubility — through our partnership with Solubility Company. This gives our clients a clearer picture of how their drug substance will behave and allows us to de-risk projects early in development.
Some companies specializing in spray drying or hot melt extrusion claim they can solve Class 2 solubility challenges, but in most cases, that’s overkill. Those methods require developing complex analytical methods and take weeks to characterize, whereas micronization is a straightforward, well-established process that delivers results much faster. Additionally, amorphous solid dispersions tend to be less stable than crystalline forms, meaning there’s a risk of recrystallization, hot spots, and performance inconsistencies over time. Scalability is another challenge — finding capacity for spray drying or hot melt extrusion can be a nightmare.
With micronization, you get a stable, homogeneous crystalline form with a predictable, well-understood process. It’s a headache-free solution that’s scalable and widely accepted from a regulatory perspective. If your problem is a Class 2 molecule, micronization is almost always the most efficient, reliable, and cost-effective approach.
DA: Beyond the obvious practical advantages to Microsize itself, how does having that in-house capability to manufacture your own jet mills provide unique benefits to your customers?
TJH: The biggest advantage is that we’re true specialists, and that depth of expertise allows us to troubleshoot problems earlier and more effectively than most. We’ve seen just about every type of molecule, formulation challenge, and process variability out there, so we can anticipate and solve issues before they become roadblocks.
When you work with a generalist, you typically get a one-size-fits-all solution, and you’re forced to work around its limitations. But because we manufacture our own jet mills, we have far more flexibility to tailor the process to each molecule’s specific needs. That means we can scale more efficiently, increase throughput, reduce variability, and ensure better reproducibility.
Our ability to customize extends down to the finest details. We can adjust nozzle angles and diameters, modify venturis to optimize powder feed, and even switch out chamber materials — using stainless steel or ceramic, depending on the application. We also have mills of every size, allowing us to seamlessly scale from small development batches to commercial volumes without having to switch to a different supplier or revalidate the process.
Ultimately, having this level of control gives us a much broader toolbox to work with, which translates to better outcomes for our clients. We’re not locked into a single way of doing things — we can adapt and optimize based on the unique properties of each drug substance. That’s a huge differentiator.
DA: Is there anything else you can share about your U.S. facility?
TJH: Absolutely. One of the key aspects of our facility is that we have a dedicated developmental wing that operates separately from our GMP manufacturing areas. This includes Ph.D.-level onboarding scientists, dedicated suites, separate equipment, an independent analytical lab, and its own data network.
By keeping non-GMP development completely separate, we create a streamlined, highly technical onboarding process where our team can work closely with clients in a way that speaks their language. At the same time, because development and GMP manufacturing are housed within the same facility, the tech transfer process is seamless. We’ve structured everything physically, digitally, and from a quality systems perspective to ensure a smooth transition from early-stage work to full GMP production without any disruptions or cross-mixing.
DA: How would you characterize Microsize’s company culture and the team you have assembled?
TJH: One of the biggest strengths of Microsize is the experience level of our team. Despite being a small company, our employees have incredible longevity — our average tenure is approaching two decades. That applies across the board, from floor-level operators to project managers, plant managers, and even executive leadership, including our COO and myself. That kind of stability is rare, and it speaks to both our work environment and the team-based culture we’ve built.
One thing we consistently hear from clients is how clean and well-organized our facility is. Given that we work at a scale that generates a lot of fine powders, people are often surprised at the level of precision and care we maintain. We take pride in that — it’s part of our DNA.
Another key differentiator is how easy we are to work with. Most of our employees don’t just stick to a single role — they have a broad understanding of the entire operation, which makes everything more efficient. Clients don’t have to navigate a maze of silos to get answers. Whether they’re here for a quality audit, a process development trial, or just checking in on their project, they’ll get clear, informed responses quickly. Even at the executive level, we’re hands-on — I can step in and have a meaningful conversation on almost any aspect of the business because I’ve been involved in all of it.
DA: As BCS Class 2 compounds continue to dominate pipelines, how do you see demand for micronization evolving over the next few years? Will Microsize remain focused on its core capabilities, or are you exploring adjacent areas to expand into?
TJH: We’re definitely committed to our core competency — micronization will be in high demand for the foreseeable future and will always be our primary focus, so that’s where we’ll continue to invest and grow. That might mean scaling up our operations and expanding our number of containment suites to keep pace with increasing demand.
At the same time, we’re building an ecosystem around micronization by incorporating ancillary solubility-enhancing technologies. One example is SoluMatrix, a dry powder nanosizing process. While it’s owned by a partner, we run it in-house because of our hands-on approach and strong facility infrastructure.
We’re also working with Austin PX, which has transferred its proprietary Kinetisol technology into our facility. Kinetisol is a novel method for producing amorphous solid dispersions, and they’ve chosen to work with us because of our high-touch service, quality systems, and facility capabilities. Rather than trying to develop these technologies ourselves, we’re leveraging our expertise and infrastructure to support them, allowing us to remain focused on what we do best while expanding our service offerings.
Additionally, we’ve collocated Solubility Company’s advanced characterization technology within our facility. This integration significantly compresses timelines, enabling us to go from understanding a drug substance’s properties to performing optimization trials and full-scale production — all under one roof. What typically requires three different vendors can now be handled in a single, seamless workflow.
This ecosystem approach is something we’ll continue to build on. We’re open to additional partnerships in the bioavailability enhancement space and will keep adding complementary technologies through collaborations rather than vertically integrating everything ourselves. That way, we can maintain our focus on micronization while offering clients a broader range of solutions.