Active Pharmaceutical Ingredient (API)/ Excipients Powder Granule Sizing
Drug companies spend years developing formulas for how ingredients should be combined into pills and other medications. They need to ensure the quality of the ingredients, as well as the right proportion of each, is combined to make an effective product. These drug formulas go through years of research and discovery, formulation development, and stability and particle size analysis testing to perfect the formula for the final drug.
Drugs have 5 types of ingredients
- Active Pharmaceutical Ingredient (API) this is the key component that provides the relief
- Excipients are other non-active ingredients in the drug
- Diluents are inactive fillers that help the drug reach a reasonable pill size
- Disintegrating agents help regulate when the tablet will dissolve in your body
- Binders help hold the drug together
The final drug needs to have the same proportion of each type of ingredient for consistency in efficacy and dosage.
Excipients, diluents, binders, and APIs are some of the raw materials combined into the pills you may take every day. These raw materials arrive at a drug manufacturing facility from a raw material supplier and must be tested for quality against specifications. Drug companies test the density and particle size distribution of these ingredients to verify for their drug formulas.
Figure 1: Optimum distribution for each API, excipient, and diluent is analyzed
Think about the life cycle of a drug you take:
- Raw materials are combined into a pill according to a specific formula
- This pill is tested to ensure it meets particle size distributions set in the formula
- The pill is then packaged and shipped all over the world
- You find a container of the pills at your local pharmacy
- When you open the container they’re all solid pills, there are no crumbles of broken pills
- You take the pill and it dissolves to release APIs at the correct time in your body
- The APIs do what they were intended to do so you feel relief
The formula this drug was created from is specific enough to consider the entire life cycle of the drug. The pill doesn’t break apart during shipment because the binders in the pill are balanced to hold the pill together over a certain period of time. The surface area coating of the pill is designed to withstand the journey it takes through your body, possibly withstanding stomach acid and other substances. When you take the pill it dissolves to release APIs at exactly the right time to provide you relief. This specificity is guaranteed via testing each component of the drug ingredients, verifying the proportions of these ingredients and final drug make-up.
Why size analysis matters
If the particle size is less than the formulation calls for, you could have more of the active ingredient working in a drug. Think about the surface area of a bowling ball compared to that of 30,000 marbles. The surface area for the 30,000 marbles is going to be much larger than that of the bowling ball. If you have a smaller size API that would result in a greater impact of it because it would have a larger surface area. The rate of dissolution in the body is determined by the particle size. How fast the API dissolves is increased with the smaller particle size because it has a higher surface area to dissolve. If the surface area is too small it may dissolve in the wrong part of the body. This could be dangerous for patients, which is why it’s so critical to test the particle size of APIs.
How ingredients are tested
Particle size analysis of ingredients using the LS 13 320 series instruments provides a distribution to compare against a pre-set standard for the drug formula. The Dry Powder System (DPS) or “Tornado Module” uses vacuum and cyclonic action to gently pull the particles. The sample is provided into the instrument via a graduated cylinder. The tornado module hovers over the cylinder and rotates the powder, creating a cyclone. The tornado module creates high sheer at a low velocity as the particles are pulled through the center of the nozzle. Shear disperses aggregates, or clumps of particles, so we can analyze their particle size individually.
Users select obscuration prior to running the instrument. The DPS module maintains the determined obscuration through a feedback loop while pulling particles. If obscuration is set too high, multiple scattering occurs due to too many particles going through at one time, which results in an incorrect particle size.
Systems that leverage pressure to push particles frequently have more fracture or breaking of particles. These drugs, or organic molecules, are very fragile, so they’re susceptible to fracture when moving at high velocity and interacting with tubing, right angles, and other instrument components. This fracture of particles affects the particle size being analyzed. It’s important to not fracture particles and count them individually in order to get an accurate understanding of particle size for drug formulation.