Determining Factors for Particle Size of a Tablet Formulation
What are the determining factors for achieving the correct particle size distribution of a tablet formulation? I recall some 30 years ago being taught that the general rule of thumb is: particle size distribution needs to be small enough to go through an 18 mesh screen yet big enough as to not go through a 200 mesh screen. While machine type and condition play a role, the following list of items should also be considered.
Flowability: Generally speaking the smaller the particle the worse the flow. Compare powdered sugar with granular sugar. The fine small particles in powdered sugar aide dissolution but not flow.
Feeder clearance: Particle size must be larger than the feeder clearance to prevent leakage.
Die table run-out: If die table run-out increases, feeder clearance and particle size must also increase proportionately. To check run-out, use a dial indicator to determine the variation of the die table.
Die fill: Wide variations in particle sizes can cause inconsistent fill volumes.
Weight control: Final volume is final weight. Larger particles pulled out of the die can reduce the final weight. Fine particles require more precise scrape-off and increase the need for a good scraper blade.
Compressibility: Improves with increased particle size and decreases as particles become smaller and smaller. Small particles have less ability to lock together during compaction.
Hardness: Smaller particles are more sensitive to over-compression.
Ejection force: Small particles decrease interstitial space and increase drag and friction.
Lubrication levels: In general higher percentages of small particles require increased quantities of lubricant. Magnesium stearate is the most commonly used lubricant and should be de-agglomerated before use.
Disintegration & Dissolution: Small particles decrease disintegration time, and increase dissolution.
Friability: Larger particles usually lock together better which results in reduced friability while small particles often increase the potential for failure (higher friability).
Electro Static effects: Electro static charge is increased as the percentage of small particles increases.
Dust control: Fine particles create a dusty operation, creating a need for frequent production stoppages and press clean-ups.
Environmental conditions: Many products are hygroscopic and sensitive to heat. Variations in room conditions can result in poor flow, compression and ejection conditions.
Lamination & Capping: Small particles are the heart of the most common defects.
Punch lubrication: Dust and super fine particles become airborne and combine with the oils and greases which can produce black specks in tablets.
Tooling condition: Punch tip & die clearance are designed to control air release allowing for improved compaction.
Machine condition: Cleaning and maintenance are downtime issues. A high percentage of fine particles and dust increases the potential for greater wear, increased cleaning frequency, reduced yield, greater particle segregation, and more tablet defects.
Cost: Fines (small dusty particles) increase operating costs, require increased levels of dust collection, decreased yields, increased frequency of cleaning, and generate greater machine & tool wear. Reducing fines will improve tablet quality.
Summary: Establishing an appropriate particle size distribution will improve tablet quality and will reduce overall costs in the long run. Fine dusty particles are the source of most tablet defects.
Posted by Mike on March 9th, 2009 :: Filed under Tableting
Tags :: compressibility, disintegration and dissolution, dust control, electrostatic effects, flowability, friability, hardness, lamination and capping, Particle Size, particle size distribution, punch lubrication, tablet, tablet formulation, tablet press, weight control