A Modelling-based comparison of IVRT and synthetic-membrane permeation for early formulation screening

Abstract

The development of topical drug formulations typically requires reliable assessment of both drug release and permeation characteristics. In vitro release testing (IVRT) is routinely used for quality control and early screening, while in vitro permeation testing (IVPT) has been commonly used as the standardised approach for evaluating skin permeation performance. However, the extent to which IVRT can anticipate IVPT outcomes remains insufficiently quantified when both experiments are conducted under same conditions. Here, using fifteen ibuprofen formulations previously characterised by IVPT on a Strat-M membrane, we performed IVRT with a nylon membrane and examined the IVRT–IVPT relationship from correlation, predictability and structural-consistency perspectives. IVRT release rate exhibited a strong positive association with IVPT steady-state flux (Pearson r = 0.95, R² = 0.92, p < 0.001), and largely preserved formulation ranking (five of the top six IVRT formulations were also top-ranked in IVPT). Gaussian process regression further revealed a highly aligned similarity structure between IVRT- and IVPT-based models (kernel alignment = 0.97). This suggests that both experimental models capture an almost identical structural representation of the formulation space, even though their response variables differ. Combined with repeatability and discriminatory capability of IVRT, these results support IVRT as an initial screening tool prior to conducting more resource-intensive permeation evaluations.