Relationship between drug percolation threshold and particle size in matrix tablets

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Previous qualitative research indicated particle size significantly affects percolation thresholds.
• Existing theoretical models offer only qualitative explanations for this phenomenon.
• Quantitative data is needed to fully understand particle size influence on drug release.

Purpose of the Study:

• To conduct the first quantitative investigation into the influence of particle size on drug percolation thresholds.
• To establish a precise relationship between drug particle size and percolation threshold values.

Main Methods:

• Matrix tablets were prepared using potassium chloride (KCl) as the model drug and Eudragit RS-PM as the matrix.
• Five distinct KCl particle size fractions were utilized, while Eudragit RS-PM particle size remained constant.
• In-vitro drug release assays were performed, and drug percolation thresholds were calculated using the Bonny and Leuenberger method.

Main Results:

• A direct linear relationship was identified between the particle size of the drug (KCl) and its corresponding percolation threshold.
• This quantitative finding supports and expands upon previous qualitative observations.

Conclusions:

• The study confirms the significant impact of drug particle size on percolation thresholds.
• This linear relationship has critical implications for the design of pharmaceutical solid dosage forms.
• Percolation threshold may become a valuable preformulation parameter if this linear behavior is broadly applicable.