The dried granulation was mixed with talc and magnesium stearate in a cone blender for 2 min after each addition. The tablets were manufactured with a single-punch tableting machine, Diaf (Denmark), to a weight around 400 mg. Appropriate settings were applied to ensure a good hardness and weight of the tablets. Hardness and friability were measured according to US Pharmacopeia methods. All tablets achieved a hardness

over 5 kp and a friability less than 1%, except for those containing high amounts of SDS (≥10 wt%), which were www.selleckchem.com/products/LBH-589.html too soft (hardness <5 kp) and had a poor friability (>1%). Dissolution experiments were carried out at 37 °C in a USP dissolution apparatus II (Prolabo Intelligent dissolution tester Novakemilab, Sweden) with a paddle speed of 100 rpm. Samples were continuously withdrawn and transferred by means of a pump to a spectrophotometer (Cary 50 Bio UV–visible,

Varian, Australia) which measured the ibuprofen concentration in the vessels as the absorption at λ = 222 nm. From the measured UV absorbance the concentration of ibuprofen and, hence, the fraction released in the dissolution medium, could be determined. Each USP vessel was filled with 800 mL of dissolution medium. The media used were 0.1 M phosphate buffered solution, pH 7.2, and GSK J4 mouse water deionised in a Milli-Q water apparatus. The pH of the water solution was not monitored during why dissolution nevertheless it is likely that pH

will change during dissolution. Tween80 and bile salts were added to buffered solution in the following concentrations 10 g/L and 7.14 g/L respectively (similar to the conditions in the intestine at fed state [60]). For SDS varying amounts were added, yielding concentrations between 0–10 mM (phosphate buffered solution) and 0–20 mM (Milli-Q water). The amount of SDS added to the tablets represents a concentration in the bath of maximum 0.4 mM, which is below the CMC for SDS. Tablets were weighed prior to the start of the experiments. From this the total amount of ibuprofen in a tablet was calculated. For tablets dissolving in Tween80 and crude bile salts the absorption from the spectrophotometer could not be used due to the large absorbance from the solutions. Instead aliquots (V = 1 mL) were manually withdrawn from each vessel at specified time intervals and analyzed with HPLC (HP Series 1050), using a flow of 0.4 mL/min on a reversed phase Acclaim RLSC C18 2.2 μm, 120 Å, 2.1 × 50 mm2 column. The HPLC detected the ibuprofen as the UV absorption at λ = 222 nm. For samples containing Tween80, an isocratic solution with 40% ACN and 60% water with 0.1% acetic acid was used. Samples containing bile salts were mixed with AcN prior to analysis (50/50 mixture) and analysed with an isocratic solution of 35% ACN and 65% water with 0.1% acetic acid.