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Article / Aug 25, 2023

Nasal-PAMPA: A novel non-cell-based high throughput screening assay for prediction of nasal drug permeability

Authors:
  • Patricia Henriques
  • Joana Bicker
  • Soraia Silva
  • Slavomira Doktorovova
  • Ana Fortuna
Source:
International Journal of Pharmaceutics (2023), 643, 123252

In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA), a high throughput screening tool, has been applied to evaluate drug permeability across several barriers such as the skin or blood-brain barrier. Herein, a new nasal-PAMPA model was optimized to predict nasal permeability, using a biorelevant donor medium containing mucin. The apparent permeability (Papp) of 15 reference compounds was assessed in six different exptl. conditions, and the most discriminating and predictive model was applied to a test drug (piroxicam) and mucoadhesive powder formulations loading the same drug. The model with 0.5% (w/v) mucin in the donor compartment and 2% (w/v) phosphatidylcholine in the lipid membrane accurately distinguished high and low permeable compounds Addnl., it exhibited the highest correlation with permeation across human nasal epithelial cells, R PMI 2650 (R2 = 0.93). When applied to powder formulations, this model was sensitive to the presence of mucoadhesive excipients and the drug solid state. Overall, the nasal-PAMPA model was more rapid than cell-based assays, without requiring specialized training or equipment, showing to be a promising in vitro tool that can be applied in drug and formulation screening for nasal delivery.

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