How Jet Milling Improves Pharmaceutical Particle Size Reduction

Pharmaceutics, like all branches of pharmacology, is heavily regulated. Remaining compliant centers around maintaining the highest standards of quality, safety, and reliability. 

Active pharmaceutical ingredients (APIs) and excipients in product formulations need to unfailingly perform to these standards. Otherwise, patients, healthcare professionals, and pharmaceutical manufacturers could be put at considerable risk.

To ensure consistent product performance and efficacy, active pharmaceutical ingredients (APIs) and excipients must behave in predictable, repeatable ways. Particle size reduction directly impacts the bioavailability, solubility, flowability, texture, and shelf life of pharmaceuticals — making your toll processing partner’s expertise in particle technology and jet milling central to successful, compliant outcomes.

Jet Milling and Particle Size Reduction

In broadest terms, particle size reduction makes solid particles uniformly smaller in order to work most effectively in delivering specific pharmaceutical product characteristics such as compression, dissolution, and flowability. Jet milling is a common solution.

Jet mill particle size reduction uses high-pressure, compressed gas to create high-velocity collisions between particles of raw material. These collisions fracture the particles into smaller pieces.

Final particle size dictates which of the two jet mill models will be used:

• Fluid bed jet mills (FBJMs) have built-in air classifiers that can be precisely adjusted to the desired particle size and shape
• Circular (or spiral) jet mills have internal classification action within the grinding chamber

Jet milling doesn’t generate heat like mechanical milling methods do, so softer powders and sensitive materials such as those often found in pharmaceuticals are good candidates. As particles are reduced to a finer scale for formulations, managing how they are processed is imperative to ensure proper efficacy and yield. That’s where particle size classification and distribution come in.

The Science of Particle Size Classification

Particle size classification is an exercise in separating particles that meet specified size and shape requirements from other particle groups during particle size reduction. How the particles are classified depends on the milling method used, but common practices include:

• Air classification uses high-speed, nozzle-fed gas to accelerate particles, causing collisions and fracturing within a spiral jet mill until the particles reach a size that meets the preset air classification specifications
• Fluidization suspends particles in a grinding chamber pressurized by forced gas and gravity. Particles in the desired size range are collected in a classifier, and the balance is released for further jet milling until they meet requirements
• Screening passes particles through a mesh or screen to separate particles for size classification
• Sieving is much like screening, but the method relies on particles being shaken in a mesh sieve to separate particles for size classification

Particle size classification isn’t arbitrary. The highly precise process is a necessary step in reaching desired particle size distribution and, ultimately, product efficacy.

The Importance of Particle Size Distribution

Dosing can be ineffective if the amount of an active ingredient in a drug is misaligned within the formulation. Users may not get the full benefit of the pharmaceutical, which can cause frustration and brand mistrust.

It’s only through particle size classification and strict attention to particle size distribution that these challenges can be overcome. Particle size distribution ensures that active ingredients are incorporated into a formulation in the quantity and density required for optimal product quality and performance. Essentially, the smaller the particle size the greater the surface area covered. 

How Particle Classification and Distribution Work Together

Particle size classification and particle size distribution aren’t mutually exclusive. Effective distribution can’t happen without classification, and neither one can be accomplished without the help of an experienced toll processing partner.

Having a toll processor handle particle size classification and distribution is more than a value-add. Particle classification and distribution inextricably link the quality and performance of pharmaceuticals. A toll processor that demonstrates excellence in proven methods of particle size reduction augments the desired outcomes and can also help steer clear of possible obstacles such as flowability concerns.

Inaccurate particle classification, poor particle size distribution, and potential particle clumping (or agglomeration) can all impede flowability. This performance failure can lead to ingredient separation and sedimentation, potential dosing issues, and a lackluster user experience that could mitigate brand success.

A toll processor with jet milling expertise can help prevent adverse outcomes. Being able to back that expertise with practical knowledge and experience in the pharmaceutical industry makes them a standout choice for partnering with pharmaceutical manufacturers.

5 Ways CPS Helps Pharmaceutical Manufacturers Leverage Jet Milling

Custom Processing Services has a proven track record with pharmaceutics.

Over the years we have identified ways that our jet milling services optimize pharmaceutical particle size reduction and benefit manufacturers in 5 key ways:

1. Enhanced product properties and performance: The average particle size range for jet milling is 1 to 10 microns (referred to as micronization) — and capabilities can also accommodate much smaller particles measured in nanometers, or larger particles in excess of 10 microns. Fine particle size reduction increases the surface area and, ultimately, improves performance of dissolution rate, appearance, taste, texture, and other properties the manufacturer might identify.
2. Virtually no contamination risk: Jet milling doesn’t depend on mechanical processes or grinding media to achieve particle size reduction. High pressure compressed air powers high velocity collisions that cause particle fractures and ultimately smaller, uniform particle size. 

Without moving parts in the grinding chamber, there is no wear and tear on the equipment that may introduce foreign matter, and the simplified mill design is easy to clean and sanitize. Contamination risk is negligible, and virtually eliminated with the extra measures taken for pharmaceutical particle size reduction, specifically clean room procedures, stainless steel equipment, and the use of purified/pressurized air during jet milling.

1. Consistent, repeatable outcomes: CPS is outfitted with the most up-to-date jet milling equipment and advanced technologies. As such, even the finest of particle size reduction projects are handled with ease, and manufacturers are assured of consistent, repeatable outcomes — a mainstay in pharmaceutical product performance.

Further, CPS has a variety of smaller scale equipment that lends itself to in-house sample testing. Manufacturers can run tests on a small batch of raw materials to better understand behaviors and make adjustments prior to larger production runs, or use the testing to keep large-scale particle size reduction projects on track with targeted results.

1. Improved quality control: Trained designers, engineers, and operators make up the core of the CPS team, and our GMP facility makes them even more effective. Underpinning everything is CPS certifications: GMP ISO 9001, FSSC 22000, Hemp US FDA cGMP, PA Certified Organic, Kosher, and Halal. Regimented certification and regulatory compliance procedures, documentation, and reporting translate to strict quality control at every process step.
2. Streamlined management of supply chains and costs: CPS offers end-to-end custom toll processing services that can help pharmaceutical manufacturers take products from raw materials to end users without having to manage vast supply chains. Engineering, lab, repackaging, logistical services, and other in-house capabilities create time and cost efficiencies that other toll processors may not be able to offer.

Pharmaceutical manufacturers can’t take a lax approach to achieving product formulation goals — or to the toll processor they entrust with particle size reduction. There is simply too much at stake.

In conjunction with expertise in precise particle size reduction, pharmaceutics regulations typically require manufacturers partner with a toll processor that’s in compliance with the FDA’s Current Good Manufacturing Practices (cGMP). Objectively evaluate cGMP milling service providers and explore their efficiencies using the information in the Food & Pharma Guide to Jet Milling & Advanced Particle Size Reduction. Download your copy to get the details.