Here are 10 practical tips you need to know:
Eligibility: The BCS pathway is for Immediate-release oral products for systemic action – not MR/ CR, or other administration routes.
Methodology: Equilibrium solubility experiments using shake-flask method- you need to sample over time until the concentration stabilizes. Alternative methods can be used- but with clear justification.
Dose-based solubility classification: “Highly soluble” = highest single therapeutic dose is completely soluble in ≤ 250 mL aqueous media across pH 1.2 – 6.8 at 37 ±1°C. If the ‘highest single therapeutic dose’ doesn’t meet the 250 mL criterion, but the highest reference product strength does, ICH M9 allows the pathway with supporting justification.
pH Control: Adjust buffers at 37°C, verify pH after API addition and at the end of the equilibrium solubility study to ensure the study is conducted under the specified pH. pH should be adjusted if necessary.
Fix wetting mechanically, not chemically: Floaters or agglomerates? Use glass microspheres/ sonication. No surfactants or organic solvents allowed as they bias the solubility claim.
Filter effects: Check filter effects by targeting 98 – 102% recovery. Otherwise switch filter type or centrifuge.
Prove equilibrium: Don’t assume “24 h”. Sample across time (e.g., 2–72 h) until consecutive points don’t meaningfully deviate (~10% is a useful guide). These experiments should demonstrate that solubility is maintained over the relevant timeframes to accommodate the expected absorption duration.
Stability: Monitor stability across pH using a validated stability indicating method (often HPLC); If the API shows > 10% degradation over the solubility assessment, solubility can’t be adequately determined and the API cannot be classified.
Samples: Minimum 3 replicates at each solubility condition/ pH. Classification is based on the lowest solubility in the pH range
Literature references: Literature can support your work. But it doesn’t replace a properly executed equilibrium solubility dataset.
Read also: BCS Classification of Drugs and Its Significance
Resource Person: Pearl Pereira Nambiar
