Case Study 601 Batch-to-Batch Variations
This case study by Surface Measurement Systems investigates three chemically identical batches (A, B, C) of a quick‑release painkiller supplied by Nycomed Pharma. Using infinite‑dilution Inverse Gas Chromatography (iGC SEA) at 0 % RH and 303 K, the study measures dispersive surface energy (via alkane probes) and specific free energies of desorption for polar probes (dichloromethane, 1,4‑dioxane, ethyl acetate, ethanol). While dispersive surface energies are similar across batches (~43–47 mJ·m⁻²), specific free energies differ markedly, following the order A > B > C. These differences mirror the dissolution rates measured for the batches (A = 95.9 % within spec, B = 84.9 % just outside, C = 32.3 % massively outside). The study concludes that iGC SEA is a sensitive tool for detecting batch‑to‑batch surface‑chemistry variations, that wet processing (used for batches A and B) enhances acidic/basic surface sites and thus dissolution, and that specific free energy values (especially for ethanol, ethyl acetate, and 1,4‑dioxane) can be used to predict whether a batch will meet dissolution specifications.
Topics
Problem Statement: Batch‑to‑Batch Variability in Pharmaceutical Dissolution
Describes the industry challenge of inconsistent dissolution rates among chemically identical drug batches and the need for sensitive analytical techniques.
Application of Infinite‑Dilution iGC SEA for Surface Energy Characterisation
Introduces iGC SEA as a high‑sensitivity method that isolates interactions with the highest‑energy surface sites, enabling detection of subtle surface‑chemistry differences.
Experimental Protocol: Sample Preparation, Column Conditions, and Probe Selection
Details the column packing, dry equilibration, temperature, probe series (alkanes for dispersive energy, polar probes for specific free energy), and analytical software used.
Quantitative Findings: Dispersive Surface Energy Uniformity vs. Specific Free Energy Divergence
Presents measured dispersive surface energies (~43–47 mJ·m⁻²) showing little batch variation, and specific free energies of desorption that differ significantly (A > B > C) across all polar probes.