Introducing Particle Size Determination
Particle Size determination has a significant role in the effectiveness, stability, consistent quality and delivery of medications. Whether dealing with small or large molecule formulations, understanding and controlling particle size is essential for optimizing drug performance. From enhancing bioavailability to ensuring dosage accuracy, the impact of particle size spans various aspects of drug development.
The Impact of Particle Size
If the particles of a drug powder are not dissolved in the formulation their size distribution will affect the efficacy of the formulation. The assortment of such formulations is wide: suspensions, solid oral dosage formulations (tablets, capsules, powders), dry powder inhalers, nasal sprays, topical delivery systems such as creams and ointments, and other delivery devices. The dissolution of drug particles directly affects absorption in the gastrointestinal tract. Inadequate dissolution due to improper particle size distribution can lead to reduced efficacy and unpredictable therapeutic outcomes.
Additionally, particle size plays a crucial role in the stability of pharmaceutical formulations. Smaller particles have a larger surface area, which can accelerate chemical degradation processes, compromising the overall stability of the drug product. Therefore, controlling particle size is essential for maintaining the integrity and shelf-life of pharmaceutical formulations.
The particle size of the protein and peptide formulations is closely linked to their secondary structure, making it central physical property for toxicity, efficacy, and safety of such products.
Formulation scientists aiming at oral formulation should consider different aspects to decide on the drug particle size distribution.
Aspects to consider for drug development
- Particle size reduction. This is vital for enhancing the bioavailability of BCS class 2 and 4 molecules, which are low soluble and have been increasing in number over the past decade. It speeds up dissolution rates, aiding absorption in the gastrointestinal tract, particularly for compounds with low solubility. This optimization boosts drug effectiveness by ensuring better absorption and efficacy.
- Uniform distribution of particles. This is crucial for ensuring consistent dosage within tablets or capsules, thus promoting dose accuracy and patient safety. If the dose is small one large particle can change the content of tablet so that the patient will not get exact amount needed.
- Flowability. Particle size also affects flowability of powder during the manufacturing process. Smaller particles tend to adhere stronger to each other and to container walls, potentially causing challenges in production.
- Stability. Particle size influences the physical and chemical stability of drugs. Smaller particles have a higher surface area, which can accelerate chemical degradation processes, compromising the overall stability of the drug product.
To summarize all these, the effect of particle size distribution must be carefully studied, optimized, specified, and controlled throughout the pharmaceutical value chain. This includes all phases from discovery and clinical studies to marketing applications and commercialization, ensuring the final product meets quality standards and regulatory requirements.
How well will your drug perform?
Overall the particle size distribution affects following drug performance attributes.
- Bioavailability
- Dissolution
- Efficacy of delivery (crucial for dry power inhalers)
- Fine particle dose consistency (crucial for dry power inhalers)
- Appearance
- Flowability
- Content uniformity
- Packing density and porosity
- Processability
Particle Size – not only for quality, but for innovation
Understanding particle size is not only crucial for ensuring the quality and consistency of pharmaceutical products but also for innovating new drug delivery mechanisms. Please find the following examples.
- Targeted Drug Delivery. Nanotechnology utilizes particle size manipulation to create systems capable of targeting specific sites within the body, for improving therapeutic outcomes and – a big benefit for the patient – reducing side effects.
- Enhanced Solubility and Absorption. Techniques like micronization and nanonization are employed to increase the solubility of poorly soluble drugs. They are enhancing their oral uptake and effectiveness.
Conclusion
The determination of particle size is a fundamental aspect of pharmaceutical science that affects nearly every facet of drug development and delivery. It is important to understand this not only from the point of view of the medicine consistent quality but proactively use as a tool and explore the possibilities it gives to improve and enhance the medication to reach the goal.
But besides all this, the most important is to underline, that the determination of Particle Size is of great value for patient security.
The content is based on: Karin Lilitorp, Søren Lund Kristensen & Thomas Andresen: Determination of particle sizes in the PHarmaceutical industry – A practical guide. BoD – Copenhagen, Denmark; 2014.
