Particle size reduction techniques such as micronization are an essential aspect of pharmaceutical manufacturing operations – and their importance continues to grow.
Micronization and other particle reduction techniques are a mainstay in addressing poor drug solubility. Once an exception rather than a rule, most new drug compounds today are highly insoluble. Reducing the size of particles increases the dissolution rate which improves bioavailability, and hence efficacy.
Micronization has become the go-to strategy to deal with poorly soluble compounds.
Since it is an inexpensive means of achieving increased bioavailability during efficacy trials, many small companies with limited budgets will micronize poorly soluble APIs. In some cases, it is far more practical than spending significant capital on formulation R&D at an early stage.
Challenges with Particle Size Reduction and Drug Compounds
Micronization generally is not without its risks. Changing a compound’s particle size can change a drug’s properties (e.g., surface area and porosity), altering performance characteristics, stability and downstream processability. Manufacturing techniques must be carefully chosen to avoid impacts on safety or efficacy.
Targeting Not Just Size, But the Size Distribution of Particles
When considering a drug compound’s target particle size, it is important to ascertain both the ideal physical size of each particle as well as the tightness of the distribution of those particles (particle size distribution, or PSD). For example, drug compounds often require a particle size range of 2-20 microns, with a very narrow distribution to minimize both fines and oversized particles.
Selecting the Right Particle Size Reduction Technique
There are a wide range of particle size reduction techniques available to the pharma industry, but when the altered drug property issues discussed above come into play (and they often do), the options narrow considerably.
One technique we frequently employ is wet mill micronization, which is tailor-made for those compounds vulnerable to the impacts of processing.
Advantages of Wet Mill Micronization
Wet-milling is a method of reducing the particle size of an API in suspension. It can readily achieve particle sizes (10-15 microns of mean volume) near to those of jet-mill micronization – without many of the disadvantages. Some of the advantages of wet-milling are:
Wet-Milling at Regis
At Regis, wet-milling is performed as a ‘unit operation’ in the same location as the synthesis. After wet-milling in our suites, and subsequent drying, the product is submitted to QC for full release.