Abstract
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.
Highlights
Guest Editor: Sandra KleinThe 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]
From the physical stability point of view, the drug which is formulated in an amorphous state should be preserved and stabilised to exert its solubility advantage even during the dissolution process [5]
There are only a handful of oral pharmaceutical products containing amorphous active pharmaceutical ingredient (API) that have been successfully marketed despite several decades of effort in research and development; examples include cefuroxime axetil (CA) [6], itraconazole (ITR) [7], quinapril [8], etravirine [9], zafirlukast [10] and rosuvastatin [11]
Summary
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]. From the physical stability point of view, the drug which is formulated in an amorphous state should be preserved and stabilised to exert its solubility advantage even during the dissolution process [5]. The limited commercial success indicates the challenges with the stability of the
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