Capsule Dissolution testing: Pre-treatment step and Method validation parameters

Original
dissolution 900 mL of 0.05 M sodium phosphate buffer, pH 7.5, containing 2% (w/w) sodium dodecyl sulfate (SLS)
medium (Tier 1)

Tier 2 with Step 1 (Pre-treatment step) Step 2

pre-treatment
step

Dissolution Medium A: 700 mL 0.05 M sodium phosphate buffer, pH After 15 minutes, add Medium B: 200 mL 0.05 M sodium
medium 7.5, containing 1% of pancreatin phosphate buffer, pH 7.5, containing 9% of SLS (pre-
warmed to 37.0 ± 0.5°C)
Medium volume 700 mL 200 mL (Total medium volume: 900 mL)
Testing time 15 minutes 45 minutes (Total dissolution time: 60 minutes)
What’s happening The enzyme digests the cross-linked gelatin capsule at the Subsequent addition of surfactant/ solubility enhancer
here beginning to ensure opening/ rupture of the capsule shell increases drug solubility and wettability

Method Validation Specificity: Confirm non-interference of the enzyme using pre-treatment procedure
Accuracy
Precision Should not be compromised due to addition of the enzyme
Linearity and Range
Repeatability To be verified at appropriate time points
Solution stability The stability of the enzyme in the pre-treatment dissolution medium needs to be evaluated to
optimize method performance.

Notes  The time period and volume of medium A used in the pre-treatment procedure is defined on a case-by-case basis.
 Addition of medium B should be as gentle as possible to minimize physical disturbance to the dissolution medium
flow.
 Other than adding the enzyme, the dissolution medium for the pre-treatment step and agitation should be same as
that of the original method a.k.a. Tier 1.

Pearl Pereira Nambiar/ Sept 2023