Dissolution testing for immediate release solid oral drug products containing highly water soluble drug substances (BCS I or III) may be substituted by disintegration testing, if these products have been demonstrated during development to have consistently rapid drug release characteristics, You should submit a justification if decision taken to replace Dissolution testing by disintegration as a performance test and take approval by the regulatory authority prior to implementation.
Disintegration could substitute dissolution as a performance test if a justification provided by the manufacturer that follow ICH Q6A guideline -
- Containing drugs which are highly soluble throughout the physiological pH range (dose/solubility volume < 250 ml from pH 1.2 to 6.8)
- Rapidly dissolving products (dissolution >80% in 15 minutes)
- Relation between dissolution and disintegration data
Read also: Difference Between Dissolution and Disintegration
According to International Council for Harmonisation (ICH) guideline Q6A, dissolution testing can be replaced by disintegration testing if it can be shown that the active pharmaceutical ingredient is highly soluble and the formulation is rapidly releasing.
This guidance allows disintegration to be used as an alternate method with products that meet the following criteria:
- Solid oral dosage forms intended to be swallowed (chewables and orally disintegrating tables do not apply)
- BCS Class 1 and 3 (high solubility, with high/low permeability)
- Drug cannot have a narrow therapeutic index
- Time to maximum concentration cannot be critical
- Manufacturing and previous dissolution testing support product will meet specifications
- Must meet Q=80% in 15 minutes
Drug products Containing highly soluble drug substances (Dose/solubility volume ≤ 250 ml from pH 1.2 to 6.8), the reason for the 250-ml volume for the dose : solubility ratio is that the drug product is to be ingested with a large glass of water, If the highest orally administered dose can be completely dissolved in this amount of water, independent of the physiological pH value (therefore the determination over the pH range 1–7.5 covering pH of stomach and small intestine), so solubility problems are not expected to hinder the uptake of the API in the small intestine.
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