Case Study 613 Aspirin Surface Energy and Dissolution
This case study investigates how ball milling alters the surface energetics of aspirin crystals and how these changes affect dissolution behavior. Aspirin powders were milled for 16 hours and sieved into two size fractions (75–106 µm and 150–250 µm). Both milled and unmilled samples were compacted into pellets, characterized for particle size, and subjected to USP II dissolution testing in pH 4.5 buffer while monitoring UV absorbance at 265 nm. Inverse Gas Chromatography Surface Energy Analyzer (iGC‑SEA) was used to generate dispersive surface energy heterogeneity profiles across a range of fractional surface coverages (n/nₘ) using alkanes and polar probes. Particle size analysis showed only minor differences between milled and unmilled powders, and XRD/DSC confirmed no polymorphic transformation or amorphization. iGC‑SEA revealed that milled samples possess higher dispersive surface energy at low surface coverages, likely due to defect sites or exposure of higher‑energy crystal planes created during milling. These elevated surface energies correlate with consistently faster dissolution rates for milled powders across both size fractions, despite similar bulk properties. The study concludes that surface energy heterogeneity, rather than bulk particle attributes, drives the observed dissolution enhancements, highlighting iGC‑SEA as a sensitive tool for detecting surface modifications that are invisible to conventional wetting measurements.
Topics
Experimental Workflow: Milling, Sieving, Compaction, and Dissolution Testing
Detailed protocol for preparing milled and unmilled aspirin powders, including milling duration, size fractionation, pellet formation, USP II dissolution setup, and analytical measurements (UV, particle size, XRD, DSC).
Dispersive Surface Energy Profiles Reveal Higher Energy Sites in Milled Aspirin
iGC‑SEA data showing elevated dispersive surface energy at low fractional coverages for milled samples, interpreted as defect‑related surface heterogeneity.
Linking Elevated Surface Energy to Accelerated Dissolution Rates
Correlation analysis demonstrating that the higher surface energy of milled aspirin drives faster initial wetting and dissolution, independent of bulk particle properties.