Validating Otto: a Franz diffusion cell autosampler to automate in vitro permeation studies

The Franz diffusion cell (FDC) is a common apparatus for evaluating in vitro drug permeation. It has traditionally necessitated manual sampling and refilling, which requires complex scheduling, and is time-consuming and labour-intensive. The aim of this study was to develop and validate a FDC autosampler, Otto, that could be retrofitted to generic FDCs to automate sampling and refilling. Methylene blue (MB) was used as a model drug to assess the volume consistency and accuracy of the samples. Otto achieved highly consistent sample volumes (coefficient of variation, CV = 3.2 %), surpassing the consistency of manual operation (CV = 7.4 %). The amount of MB measured across multiple sampling-refill cycles mirrored the theoretical amount, as well as the amount determined through manual operation. Otto collected up to 100 samples unattended, over 24 h, in an in vitro ibuprofen permeation study. The samples were collected into standard sample vials to integrate seamlessly with downstream analytical equipment. Otto improved the quality of the permeation data over manual sampling, by sampling automatically around the clock to effectively maintain sink condition in the FDC. It therefore offers a cost-effective, performant and reliable automation solution for permeation studies that use the FDC.