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The presentation discusses the factors controlling bioequivalence and the relevance of dissolution in the context of pharmacokinetics. It highlights the dependence of the PK profile of locally acting OIDPs on factors such as deposition, particle dissolution, drug solubility and permeability, and particle clearance.
The presentation points out that low solubility drugs with slower dissolution show PK sensitivity to regional deposition. It suggests that demonstrating PK and Dissolution equivalence may help to lessen the reliance on PD/clinical. However, it also notes that current dissolution models lack discriminatory capability, ruggedness, and stability, making it difficult to investigate the dissolution of the aerosol dose.
The presentation also discusses a claim by GSK that when salmeterol and fluticasone propionate were administered in combination by the inhaled route, the pharmacokinetics of each component were similar to those observed when the drugs were administered separately. However, the presentation shows that the Cmax was found to be significantly higher after administration of the combination-based product, and both AUC and Cmax would fail the bioequivalence PK test.
The presentation concludes with a summary of the development of an aerosol collection system (UniDose) that deposits the whole impactor stage mass (ISM) uniformly over a high surface area filter for dissolution studies. It notes that UniDose has significantly increased the discriminatory capability, ruggedness, and stability of aerosol dissolution testing. It also suggests that it’s possible to investigate the impact of raw material critical material attributes and formulation processing on dissolution, but utility to support IVIVC requires more work and input of clinical data.
