Date Published: February 13, 2019
Publisher: Springer International Publishing
Author(s): Chiau Ming Long, Kin Tang, Hitesh Chokshi, Nikoletta Fotaki.
The aim of this study is to investigate the dissolution properties of poorly soluble drugs from their pure form and their amorphous formulation under physiological relevant conditions for oral administration based on surface dissolution ultraviolet (UV) imaging. Dissolution of two poorly soluble drugs (cefuroxime axetil and itraconazole) and their amorphous formulations (Zinnat® and Sporanox®) was studied with the Sirius Surface Dissolution Imager (SDI). Media simulating the fasted state conditions (compendial and biorelevant) with sequential media/flow rate change were used. The dissolution mechanism of cefuroxime axetil in simulated gastric fluid (SGF), fasted state simulated gastric fluid (FaSSGF) and simulated intestinal fluid (SIF) is predominantly swelling as opposed to the convective flow in fasted state simulated intestinal fluid (FaSSIF-V1), attributed to the effect of mixed micelles. For the itraconazole compact in biorelevant media, a clear upward diffusion of the dissolved itraconazole into the bulk buffer solution is observed. Dissolution of itraconazole from the Sporanox® compact is affected by the polyethylene glycol (PEG) gelling layer and hydroxypropyl methylcellulose (HPMC) matrix, and a steady diffusional dissolution pattern is revealed. A visual representation and a quantitative assessment of dissolution properties of poorly soluble compounds and their amorphous formulation can be obtained with the use of surface dissolution imaging under in vivo relevant conditions.
The amorphous form has attracted increasing interest within the pharmaceutical field because its higher solubility could achieve better dissolution rate and absorption rate and increase the bioavailability of poor water-soluble compounds (1). The solubility increment of amorphous forms over crystalline states depends on the potential energy difference between these physical states (2,3). It was estimated that 10–1600 folds of solubility increment can be achieved by applying the amorphous form (4).
Surface dissolution UV imaging methodology that could be used to understand the mechanism of CA and ITR (pure APIs and their amorphous formulations) dissolution was developed in this project. From the surface dissolution UV imaging testing, the UV images of absorbance maps and contour concentration lines of the dissolved CA during the studies with media and flow rate change (SGF/SIF) revealed that CA dissolved from the compact surface as aggregates and formed a supersaturated CA solution that subsequently precipitated out. Similarly, for ITR, the supersaturation of ITR after media change drastically increased the recrystallisation of ITR on the surfaces of the ITR pure API and Sporanox® compacts which could lead to ITR crystal growth. The UV images obtained from these studies provided a visual representation and a qualitative as well as quantitative assessment of the differences in dissolution rates and concentration for the model compounds used.