How Micronization Yields Soluble, Bioavailable API Particles
Particle size plays a critical role in the formulation of drug products. The size of active pharmaceutical ingredients (APIs) and excipients is an important physical characteristic that is fundamental to all drugs, whether administered orally, topically or parenterally. The size of the active particles, along with particle distribution and the shape of the particles, impacts the aqueous solubility of drug compounds. Solubility, in turn, is a key factor in bioavailability, and hence the effectiveness of the drug.
This link between particle size and product performance is well documented in the literature. We know that reducing particle size is central to formulation of New Chemical Entities (NCEs), particularly those found during drug development to have poor aqueous solubility. Appropriate matching of excipient to active ingredient particle size is an important factor in several process steps after the final API has been developed. Particle size is also important for product stability.
This article focuses on the key role micronization technology plays in developing oral drugs or creams with active ingredients that are right-sized and evenly distributed throughout the vehicle.
Typically, when we talk about micronization, we are talking about reducing the size of particles to less than 20 microns, and producing uniform particles evenly distributed throughout. It is this uniform particle size throughout the distribution that makes each step of the process move along successfully to the next to achieve a quality end product.
PCI Synthesis has extensive solid materials handling capabilities that include various techniques to achieve desired particle size and distribution. One of the products we developed and market, synthetic GMP azelaic acid, is a good example of manipulating particle size for pharmaceutical use.
To achieve effective formulations, PCI Synthesis works closely with its customers to develop particle size specifications that intersect with our manufacturing processes and are also measurable and reproducible.
Particle size analysis
The micronization process begins with particle size analysis, which is integral to formulating and manufacturing many pharmaceutical dosage forms. Our equipment – the advanced, efficient Malvern Mastersizer 2000 – is in constant use for two purposes. Our Quality Control Lab uses the equipment to approve final finished dosage products. It is also a critical instrument during API process development.
The Mastersizer 2000 is equipped with both wet and dry measurement sampling accessories. Whether to measure wet vs. dry really depends on the nature of the material to be analyzed. Many materials need to be measured in a wet dispersion apparatus, usually when the materials themselves will be used in a wet manufacturing process known as wet blending. Certain sticky materials, or those that have a tendency to agglomerate when dry, are also measured in a wet dispersion.
For the purposes of micronization, dry measurement is usually preferable, as it also is for materials used in dry manufacturing processes such as direct compaction, dry blending, or powder coatings.
The Mastersizer can measure materials from 0.02µm to 2000µm. Automation coupled with our SOPs eliminate user variability, providing full validation documentation in compliance with 21 CFR Part 11.
Once the desired process parameters and variables as size of the chamber, feed rate and flow rate of nitrogen gas are determined, micronization proceeds quickly in an automated, heat-free process that avoids creation of any new impurities.
Micronization technology at PCI Synthesis
To meet any specific particle size requirements, our labs and manufacturing facilities are fully equipped with the following advanced equipment:
- Fitzpatrick Fitzmill Model: DASO-6
- Quadro Engineering Comil Models: 194-S, U20
- Sturtevant Micronizer Models: M2, M4
- Sweco Sifter Models: S18, S30
The technology assures that the final finished dosage products can be scaled up and manufactured time and time again.
Why manipulate particle size?
Achieving success with particle size in the laboratory helps create effective pharmaceutical drugs. Do you know someone who had an adverse reaction or no reaction to a drug? Particle size may very well have been the culprit. Being able to reduce particle size can be an important factor.