Whenever I think about transitioning a New Compound Entity to the clinic, it strikes me that it is like finding a diamond in the rough and transforming it into a ring. The Discovery group finds the diamond, while the Crystallization and Particle Engineering teams cut and polish the diamond. Finally, the Formulators set the diamond into the ring.
Micronization is, essentially, the place where Drug Substance meets Drug Product. At Lonza, we have the skills and expertise to cover the entire space. We can synthesize the API, we can conduct crystallization trials, and can micronize the material. We can also develop the formulation and deliver the supply to the clinic or provide these services on a commercial scale.
Micronization is an incredibly important step in transitioning a compound from the initial discovery into the clinic. This manufacturing technique produces APIs less than 20 microns in average particle size.
There are a few key benefits of micronization:
- Firstly, improved bioavailability. Put simply, when a material is micronized, you are breaking it up into smaller pieces, effectively increasing its surface area. This allows the material to dissolve faster, have a higher Cmax, and improve overall exposure.
- The second benefit is downstream processing. Material coming out of a crystallization rarely has a uniform particle size distribution at the desired particle size. Micronization increases the material's homogeneity before it moves on to the step where the drug product is made, leading to more uniform products.
Micronization is also important to the delivery of medicines via nonoral routes. Inhaled medication, long-acting injectables, coated implants, and ocular delivery has been steadily growing over the past few years. The inhalation delivery relies on ensuring the correct particle size and aerodynamic diameter of the drug, as this attribute ensures proper delivery and operation of the inhalation device. Additional delivery modalities rely on specific particle size criteria to control the product performance.
Micronization also poses some challenges. The bulk properties of the micronized material are different when compared to non-micronized material. The flow properties of the micronized materials may be poor and are often accompanied by a build-up of electrostatic charge due to the increased surface area. Other challenges include the conversion of the API to a different crystalline polymorph or the formation of amorphous content.
Therefore, the optimal working conditions need to be determined for each process. For us, the whole journey always begins with a conversation about the goals of the micronization campaign. It continues with performing a specific risk assessment to identify all possible critical process parameters, such as the variability of raw material size, water content specifications, and knowledge about the solid-state changes. Generally, a one-factor-at-a-time approach is used to select the initial processing parameters. Design of experiments (DoE) is performed at later stages of development to define each product's design space and the normal operating range.
We can help our customers address all challenges related to jet-milling and micronization of their API, define the best working conditions suited for their target profile, and assist with scaling up the jet milling process. We take opportunities to improve the yield and throughput of material during scaling up.
Whenever we start a new project with a client, we take the time to really get to know what their goals and needs are. People are at the heart of every business relationship, and that is why we are the perfect partner for everyone, from the smallest biotech company all the way through to the largest pharmaceutical businesses.
Our Monteggio, Switzerland site offers world-class capabilities and enables a wide range of particle sizes and distributions to be created. We have the flexibility to meet every client's needs – and to fit every stage of the development journey, from clinical trials to commercialization.
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Lonza Group Ltd has its headquarters in Basel, Switzerland, and is listed on the SIX Swiss Exchange. It has a secondary listing on the Singapore Exchange Securities Trading Limited (“SGX-ST”). Lonza Group Ltd is not subject to the SGX-ST’s continuing listing requirements but remains subject to Rules 217 and 751 of the SGX-ST Listing Manual.
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