You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: ["Chemical"].

Please return the output as a JSON object of the format: {"Chemical": ["Arsenic", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].

Only output the JSON object and do not include any additional text.

Abstract:

New formulation approaches to improve solubility and drug release from fixed dose combinations: Case examples pioglitazone/glimepiride and ezetimibe/simvastatin. Low aqueous solubility is often a limiting aspect to the bioavailability of poorly soluble, but highly permeable drugs (class II compounds according to the Biopharmaceutics Classification System - BCS) administered in single drug products or as fixed dose combinations. The aim of the present series of experiments was to improve the solubility and dissolution of two fixed dose combination formulations (FDC), each consisting of two BCS class II drugs. The first FDC contained a weak acid (glimepiride) and a weak base (pioglitazone), while the second FDC contained two compounds (simvastatin and ezetimibe) that are essentially non-ionised over the physiological pH range. The formulation approaches used were as follows: (a) an inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD), (b) a solid dispersion with Soluplus®, a new highly water soluble polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer and (c) a ternary inclusion complex with both HP-β-CD and Soluplus®. Solid state analysis was performed for the pure drugs, and all formulations using powder X-ray diffraction (PXRD). The in vitro performance of the different formulation approaches, as gauged by solubility and dissolution experiments, was compared with that of the marketed products containing the respective fixed dose combinations, Tandemact® 30mg/4mg tablets and Inegy® 10mg/40mg tablets. The FDCs of the pure drugs and the marketed products showed very poor (and especially for pioglitazone, strongly pH-dependent) dissolution. By contrast, all binary and ternary inclusion complexes showed enhanced release for both drugs in the FDC. The ternary inclusion complex generated synergistic improvement in solubility and dissolution results for both FDCs. For example, in pH conditions of the fasted small intestine after a test duration of 240min, we observed 100% dissolution of both drugs from the ternary pioglitazone/glimepiride (30mg/4mg) complex formulation, whereas from the marketed formulation less than 5% pioglitazone, and only 25% glimepiride dissolved. Using the same conditions, 60% ezetimibe and 85% simvastatin dissolved from the ternary ezetimibe/simvastatin (10mg/40mg) complex formulation, whereas with less than 5% ezetimibe and 10% simvastatin dissolved after 240min, the marketed FDC formulation showed poor dissolution. Based on the results of the present study, the bioavailability of both drugs in the fixed dose combination is likely to be increased after oral administration of the new formulations, especially when the fixed dose combination is formulated as a ternary complex consisting of HP-β-CD and Soluplus®.
{"Chemical": ["Inegy", "polyvinyl acetate", "hydroxypropyl-\u03b2-cyclodextrin", "Tandemact", "ezetimibe", "polyvinyl caprolactam", "pioglitazone", "glimepiride", "polyethylene glycol", "Soluplus", "simvastatin", "HP-\u03b2-CD"]}