In Vitro Dissolution of Insulin Crystal Polymorphs at Model Conditions Relevant to In Vivo Environment

Abstract

In vivo dissolution of crystalline insulin formulations is an important step for insulin absorption in the subcutaneous therapy of diabetes, which is the most widespread. Here, data on the in vitro dissolution of three different crystalline forms of commercial porcine insulin are reported. The aim of this study was to create a model framework of in vivo dissolution of insulin crystalline formulations. In situ insulin crystal dissolution was studied at conditions of continuous undersaturation (i.e., in the absence of any free insulin around the crystals) in several types of model flood liquids, at different flooding flow rates relevant to blood capillary flows, and at a dissolution system temperature of 36 °C. Insulin crystal dissolution rate depends strongly on the flooding liquid composition and crystal type, the effects of pH and flooding flow rate being less pronounced. Results of the present study suggest a possibility for purposeful control over in vivo dissolution rates through development of particular insulin crystalline-based formulations.