Cinnarizine is a lipophilic active ingredient with poor aqueous solubility. In vivo data show a significant impact of food on its bioavailability. We developed an analytical method based on high performance liquid chromatography (HPLC) and evaluated the release of cinnarizine from tablets in media, simulating the presence of lipids in food. The developed analytical method was evaluated according to the Guidelines for validation of analytical methods ICH Q2(R2). We developed an appropriate sample preparation process for subsequent HPLC analysis. The release of cinnarizine was tested in 0.01 M HCl, phosphate buffer pH 6.8, and in SMOFlipid® mixtures with 0.01 M HCl, and with phosphate buffer pH 6.8. Dilutions were selected based on the literature, where a similar lipid medium was used in the preparation of biorelevant media to simulate the gastric fed state conditions. Dissolution tests were performed on an apparatus II at 75 rotations per minute. The concentration of the released cinnarizine was calculated using the calibration curves, prepared in each of the tested media. We analyzed the percentage of cinnarizine released in the upper lipid and lower aqueous phase of release samples. With a mass balance analysis in selected release samples, and in standard solutions, we have confirmed that the sum of percentages of cinnarizine in individual phases, approaches 100 % of the total amount of cinnarizine at each release time-point. We concluded that the release of cinnarizine in SMOFlipid® mixtures with 0.01 M HCl is faster than in mixtures with phosphate buffer pH 6.8, due to the good solubility of cinnarizine in HCl and the poor solubility in phosphate buffer. The lipids present in SMOFlipid® affect the release of cinnarizne from tablets and the distribution of cinnarizine between the aqueous and lipid phase. In less diluted SMOFlipid® mixtures with HCl, more lipids are present which slow down the release slightly. More cinnarizine is distributed into the lipid phase, but due to its good solubility in media containing HCl, a significant amount of cinnarizine is also distributed into the aqueous phase. The less diluted are SMOFlipid® mixtures with phosphate buffer, the faster is the observed release, and the higher is the percentage of cinnarizine released. In all mixtures with phosphate buffer, practically all of the cinnarizine is distributed into the lipid phase. We have proven that with different proportions of lipids and pH values of the media, we can influence the release of cinnarizine. This leads us to conclusion that by the use of the tested media, it is possible to achieve an in vitro release profile of cinnarizine, that may be representative for the fed state in vivo.
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