Willow Slusser, Nov 17, 2022 11:00:00 AM
Pharmaceutical products consist of active ingredients (APIs) and excipients — inert substances such as fillers, coloring agents, preservatives, etc. APIs and excipient formulations work concurrently within a product, with the particle sizes driving pharmaceutical blending and, ultimately, pharmaceutical quality.
How is particle size related to pharmaceutical product quality?
There is a lot made of particle size in pharmaceutical products, and rightly so. Particle size dictates how APIs and excipients behave which, in turn, determines drug efficacy. In short, a pharmaceutical must deliver predictable, repeatable outcomes. Anything less is a failure and potentially harmful.
Likewise, particle size distribution plays a pivotal role in pharmaceutical product quality. Essentially, the finer the particle size the greater the surface area covered. And more surface area coverage means enhanced product quality and performance.
Often, jet milling micronization is used to reduce particle sizes for best blending results, but exact grinding methods are aligned with pharmaceutical applications. The final form the pharmaceutical product takes can also partially decide how particle size impacts these factors and overall quality:
1. Compression
Tablets are formed by the application of pressure. How strong and how long compression cycles last depends directly on particle size and distribution. If there is an imbalance, tablet weight, quality, and dosing can be substandard.
2. Dissolution
Pharmaceutical products such as tablets and time-release capsules are somewhat performance-dependent on their ability to dissolve. Tablets generally need a certain particle size formulation in order to maintain proper shape. Particles that are too small can lead to over-compression and an inability to dissolve. Time-release capsules, too, need precision particle size in order to effectively introduce the product when and as needed, according to the formulation.
3. Bioavailability
Ingestible or topical pharma products generally need to be absorbed into the bloodstream or circulatory system to provide the intended dosage. Larger particles can inhibit bioavailability — how much medication and time it takes for a patient to receive appropriate effects.
4. Flowability
How APIs and excipients move through equipment and within capsules, liquids, etc., is all related to proportional particle size. Ingredient separation is indicative of improper flowability. For example, a liquid formulation with flowability issues may need to be vigorously shaken to partially reintegrate particles. This results in a suboptimal user experience and potential dosing and quality issues.
5. Shelf life
Particle size distribution is particularly impactful when it comes to shelf life. It influences the performance of the APIs, certain production decisions such as filtration and drying rates, and material stability during storage. Maximizing all of these factors adds up to product integrity and duration of effectiveness.
Quality processing partner, quality outcomes
Just as no two pharmaceutical drug formulations are the same, so it is with pharmaceutical ingredient blending. The constant in pharmaceutical blending, however, is the impact of drug stability, visual appeal, and efficacy.
Controlling all of these factors to consistently meet industry standards and product quality expectations is the responsibility of your toll processing partner. Their approach to raw materials milling and pharmaceutical blending processes will evidence itself in quality outcomes.
Be confident in your choice of processors. Ask these key questions of your current or prospective processing partner:
Can your process controls be audited, validated, and qualified?
If there is hesitation or a lack of demonstrated, documented proof about any part of this question — move on. The risk is too great.
Do your clean room protocols and cleaning best practices support pharma grade processing?
Multi-level cleaning protocols in clean room environments are a must, as is cGMP certification. Both reinforce the toll processor’s commitment to maintaining pharmaceutical product quality, strength, and purity.
What equipment is available for pharmaceutical blending projects?
For most pharmaceutical products, a double-ribbon blender’s low shear provides appropriate dry blending homogenization, consistency, and accuracy. However, it’s common practice to also use continuous, tumble, and vertical cone blenders. Micronization during raw material grinding prior to blending may be accomplished with jet milling.
Pharmaceutical quality and pharmaceutical blending are not mutually exclusive. Working with a toll processor with particle reduction expertise and an excellent reputation in the pharmaceutical industry is necessary for quality outcomes. It’s also a good start in finding the right toll processing partner.
Compare options with confidence using the Blending for Pharmaceuticals: A Guide for Selecting Your Trusted Toll Processor. Click the button below to download your copy now.
