A more prevalent use of biologics (which mostly cannot be orally administered) together with improved patient compliance (compared to intravenous injections) led to an increase in drug products administered subcutaneously [1]. Hence, an in vitro assay that can quantify the release of such drug products will be of great appeal in formulation development and quality control. Agarose hydrogels have been postulated to mimic certain characteristics of the subcutaneous tissue by creating a diffusion barrier [2]. This study aims at the development and optimisation of a biopredictive in vitro gel-based release assay by customization of the USP dissolution apparatus 4. Our “gel-in-cell” model employs an agarose gel in a modified flow-through cell, and was used to assess the release of insulin and the preservative m-cresol, which served as a small-molecular standard, from commercial insulin formulations, Actrapid® and Apidra®, across the agarose gel layer. Our results indicate that the model was capable of quantifying the release of insulin and m-cresol. The release of insulin from Apidra® was faster than that of Actrapid® which reflected the relative in vivo performances of the two insulin formulations [3]. The release of m-cresol was similar for both insulin formulations which was expected. The difference factors (f1) and similarity factors (f2) of insulin and m-cresol were also calculated to give some insight into the discriminatory ability of the assay. This model is in its early development stage and further modifications are expected to reflect more characteristics of the physiological environment and cater for subcutaneous drug products with different release mechanisms.

References:

1. Bittner, B., W. Richter, and J. Schmidt, Subcutaneous Administration of Biotherapeutics: An Overview
of Current Challenges and Opportunities. BioDrugs, 2018. 32(5): p. 425-440.
2. Leung, D.H., et al., Development of a Convenient In Vitro Gel Diffusion Model for Predicting the In
Vivo Performance of Subcutaneous Parenteral Formulations of Large and Small Molecules. AAPS
PharmSciTech, 2017. 18(6): p. 2203-2213.
3. Soeborg, T., et al., Absorption kinetics of insulin after subcutaneous administration. Eur J Pharm Sci,
2009. 36(1): p. 78-90.