Method for measuring mucoadhesion of ophthalmica considering regulatory aspects.

In this technical note we present an easy to use method for determining mucoadhesion for ophthalmica, easily applicable in a regulated setting. The determined value of mucoadhesion is a combination value of adhesion and cohesion force, as both are relevant to the retention of a formulation and thus its bioavailability. The method is specifically designed to test two formulations against each other to gain information on bioequivalence. We tested 14 different commercially available ocular formulations as function of their content of hyaluronic acid - a known mucoadhesive. We could find a trend of higher mucoadhesion for formulations with higher contents of hyaluronic acid in control and sample, though some samples deviate from the expected values. Furthermore, we provide background information on the qualification of the device and the method validation according to guidelines.

Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages: an opportunity for an in vitro drug screening assay.

Inflammatory bowel disease (IBD) is a widespread disease, affecting a growing demographic. The treatment of chronic inflammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput. Reliable and valid in vitro assays offer the opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the intestinal barrier and the immune response in IBD. The drug efficacy was analyzed by an LPS-inflammation of the co-culture and drug exposure according to the IBD treatment pyramid. Efficacy was defined as the range between LPS control (0%) and untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α). The release of IL-6, IL-8, and TNF-α was identified as an appropriate readout for a fast drug screening ("yes-no response"). TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine, and infliximab) with an R2 of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate establishing an "Efficacy Outcome Pathways (EOPs)" framework for drug efficacy assays. The in vitro assay offers an easy and scalable method for IBD drug screening with a focus on human data, which requires further validation. Supplementary Information: The online version contains supplementary material available at 10.1007/s44164-022-00035-8.

Development and evaluation of a quality control system based on transdermal electrical resistance for skin barrier function in vitro.

BACKGROUND: In vitro skin permeation experiments are highly relevant for pharmaceutical, cosmetic, agricultural developments, and regulatory evaluation. A key requirement is the skin barrier integrity, that is accompanied by an intact stratum corneum (SC) which implements high skin quality. A variety of integrity tests are currently available, for example, measurement of transepidermal water loss, monitoring the permeation of tritiated water and the measurement of transdermal electrical resistance (TER). MATERIALS AND METHODS: We aimed for a non-destructive examination of barrier integrity as quality control system, based on TER. Therefore, the in-house developed instrument SkinTER measures electrical resistance on excised human skin samples in a non-invasive and easy-to-use pattern. In this proof of concept study, we compared three human in vitro skin models with focus on their TER and permeation properties. The skin integrity was impaired to mimic conditions of skin during age, lifestyle (eg, shaving) or diseases (eg, obesity, psoriasis, and atopic dermatitis). The OECD permeation marker caffeine was correlated to the corresponding TER value. RESULTS: A correlation between both was obtained by having a Pearson coefficient of -0.830. Hereby, a minimum TER value for intact skin samples of ~1.77 kΩ*cm2 was suggested. Intact samples are significantly different (α = ≤0.05) to their impaired counterparts in flux and TER values. CONCLUSION: The new SkinTER instrument gives a quick and non-invasive feedback on skin quality before a permeation experiment.