API Micronization: Precision and Experience Matter

Micronization:  Precision and Experience Matter

By Guy Samburski, Senior Director of Technology R&D, TAPI

 

 

Whether it is a cholesterol-lowering tablet, an inhalation treatment for asthma, or chemotherapy to fight cancer, medicines available today are required to work quickly and more effectively than ever before. To manufacture drug products that absorb properly, it is essential to start with active pharmaceutical ingredients consisting of particles that are the proper size. Larger particles can be reduced through a process called micronization.

 

Micronized APIs can often help manufacturers overcome formulation challenges in a range of drug products, including:

  • There is an increase in number of new dosage forms which contain BCS 4 molecules (with low permeability and low solubility properties), mainly for Cancer and CNS

 

  • Inhalation therapy: including dry powder inhalers, metered-dose inhalers and nasal spray

 

  • Topical delivery dosage forms: including gels, transdermal patches, special ophthalmic preparations

 

All require small and accurate particles for effective particle size distribution (PSD).

 

Expert know-how makes the difference

Micronization requires expensive, highly-sophisticated equipment and knowledgeable experts running it to meet precise particle size specifications. We have built this in-house capability to handle micronization because we find it important to the integrity and quality of the result. Today nearly all of our manufacturing plants around the world have this capability and qualified experts on site who carefully oversee the process.  

 

The most commonly-used technique today is air jet mill micronization, which is also used most frequently at TAPI. This process uses pressurized gas to move particles at a high speed, forcing them to collide with each other and break into smaller, uniform-size particles. It’s ideal for heat-sensitive products because the temperature remains relatively constant throughout the process. Jet milling requires highly-skilled operators and specialized process engineers to produce material that meets the customer’s exact specifications.

 

Cryogenic micronization is a relatively new process and can be more effective for some materials. TAPI R&D has capabilities to use this method, which produces finer particle size for compounds that are sticky or tend to aggregate. In cryogenic micronization, an air jet mill is chilled to extremely low temperatures with liquid nitrogen, which makes the material very brittle while maintaining its crystallinity.

We have built this in-house capability to handle micronization because we find it important to the integrity and quality of the result. 

In-house micronization yields high quality results

Several engineers and 70 operators run TAPI's largest micronization facility at our API manufacturing site - Teva Tech in Israel. They oversee eight micronizers and many mills of various types. In our experience, handling micronization in-house has many benefits including:

Better quality control. Because the product is manufactured on site, we can control the quality in every step of the process, making sure the micronized material is handled and stored properly, and ensuring our stringent standards are met.

Shorter turnaround time. Micronizing a product on site can eliminate downtime caused by possible production or shipping delays from a third party.

Flexibility to generate samples. If a pharmaceutical manufacturer is not sure what size particle will work best in their dosage form, we can produce samples with different particle sizes for testing, then scale up when the customer is ready for production.

Industry expertise. TAPI has gained extensive experience in micronization over the years. Our R&D subject matter experts support our knowledgeable on-site teams and ensure they stay current on the latest industry trends and technology.

 

From time to time, customers have unique API needs that standard micronization techniques won’t address. Some of the challenges we’ve handled include:

  • Obtaining extremely small particles with a narrow particle size distribution (PSD) range and a high specific surface area with an opposed-jet micronizer

 

  • A special micronizer design to handle high electrostatic charged particles

 

  • Micronization of highly sticky material

 

In every case, we collaborate closely with the customer to develop a specialized solution that delivers a product that will work for them.

 

Although micronization has been around for many years, pharmaceutical manufacturers rely on it more today than ever before. Whether a drug product is a tablet, ointment, inhaled medication or another dosage form, particle size often matters because it can play a key role in how effectively medicines work. Even more important than the technology is the knowledge and experience of the expert overseeing it. Make sure your API provider has the know-how to deliver. In the end, it is patient wellbeing which may benefit..

 

Guy Samburski is Senior Director of Technology R&D for Teva Pharmaceutical Industries, Ltd. with more than 20 years of experience supporting pharmaceutical manufacturers with formulation, physical properties and other technological issues.

To learn how TAPI’s team of experts can meet your specialized needs, please contact us.