Development of a buccal in vitro permeation method – exploring aQbD implementation

• Published in: International journal of pharmaceutics Vol. 643; p. 123255
• Main Authors: Sena, Ariana, Costa, Alain, Bastos, Francisca, Pinto, Ana Catarina, Vitorino, Carla, Nunes, António, Simões, Sérgio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.08.2023
• Subjects: Analytical quality by design; Buccal mucosa; Critical method parameters; In vitro permeability; Permeation method; Buccal mucosa; PBS; CAA; Na2HPO4; Permeation method; Analytical quality by design; CMV; DS; ICH; UFLC; Critical method parameters; HCl; QbD; MODR; KCl; In vitro permeability; NaCl; DoE; ATP; HPLC; aQbD
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.123255

[Display omitted] •aQbD flowchart as a guidance for permeation method development;•Identification of critical parameters and impact assessment on in vitro buccal permeation method;•Optimization of study conditions to achieve an accurate and precise permeation profile;•Knowledge from this assessment can be adapted to other in vitro and ex vivo methods. The buccal mucosa is arising within the pharmaceutical landscape as an attractive option for local and systemic drug delivery, mostly due to its high vascularization, inherent permeability and robustness. Still, one of the major challenges in bringing oromucosal preparations to market remains the accurate evaluation of permeability. During pre-clinical drug development, in vitro permeation assessment is essential, and methodologies, based on the selection of a proper membrane in a diffusion cell, have become appealing alternatives to the conventional cell-based models. The development of such methods is being constrained by the number of variables - related to study conditions, setup and formulation - that need to be optimized to accurately estimate buccal permeation. The gap of knowledge over the mentioned variables may lead to long costly developments and poorly accurate methods, especially if the empirical analytical approach is used. In this paper, a systematic risk-based analytical quality by design approach was applied to the development of a buccal in vitro permeation method, ensuring that all sources of variability affecting permeation process were identified, explained and managed by appropriate measures. Researchers are guided through a step by step model, successfully demonstrating with experimental data the impact of critical variables on method’s performance.