Dissolution-permeation approach for biopharmaceutical evaluation: a feasibility study using naproxen

Abstract

Objective: Dissolution and/or release profile alone are insufficient to predict the in vivo absorption of poorly soluble drugs. Thus, permeation test becomes a critical component for biopharmaceutical assessment. Currently, none of the dissolution-permeation systems include the compendial dissolution, or provide large acceptor volumes, or are compatible with ex vivo membranes. Addressing the limitations of the existing dissolution-permeation testing systems, we propose the integration of the Ussing (permeability) chamber to the dissolution apparatus. Methods: The assembled dissolution-permeation system evaluated the effect of 5% and 10% soy L-a-phosphatidylcholine in dodecane (LiDo) and permeable membrane material on apparent permeability coefficients of naproxen, a BCS II class drug. Results: Naproxen release from the tablets reached approximately 100% within 30 minutes. Naproxen Papp across a 0.45 µm PVDF membrane was 0.91 ± 0.35 × 10-8 cm/s for 5% LiDo, and 0.75 ± 0.23 × 10-8 cm/s for 10% LiDo. The 0.20 µm PC membrane with 5% LiDo showed a Papp of 1.99 ± 0.57 × 10-8 cm/s. Conclusion: The proposed compendial dissolution-permeation system with an Ussing chamber allowed for the simultaneous determination of dissolution and permeability of naproxen. All Papp values obtained were approximately 100-fold lower than those reported in the literature. The results may have been influenced by the differences in sink conditions and permeable membrane composition. The use of a PC membrane resulted in higher permeability, compared to the PVDF membrane. Adequately improved, this methodology could be transferred for the ex vivo membrane dissolution-permeability testing.