The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilexetil by associating others assays such as stability determination, polymorphic characterization and in silico calculations of intrinsic solubility, ionized species, and electronic structures using quantum chemistry descriptors (frontier molecular orbitals and Fukui functions). For the complete biopharmaceutical classification, we also reviewed the permeability data available. The polymorphic form used was previously identified as the form I of candesartan cilexetil. The solubility was evaluated in biorelevant media in the pH range of 1.2-6.8 at 37.0°C according to the stability previously assessed. The solubility of candesartan cilexetil is pH dependent and the dose/solubility ratios obtained demonstrated the low solubility of the prodrug. The in silico calculations supported the found results and evidenced the main groups involved in the solvation, benzimidazole, and tetrazol-biphenyl. The human absolute bioavailability reported demonstrates that candesartan cilexetil has low permeability and when associated with the low solubility allows to classify it as class 4 of the Biopharmaceutics Classification System.
The bench top and refrigerator stability of donepezil hydrochloride final stock solution, that is, the mobile phase of the chromatographic method developed, composed of acidified water with acetic acid 0.20% and acetonitrile (70:30 v/v) was evaluated.The stock solution was initially prepared, then, 1 mL was aliquoted and transferred to vials (n = 3) according to the type of stability evaluated, as follows:• Benchtop stability: the effects of ambient temperature isolated and associated with ambient light were evaluated using amber vials and transparent vials, respectively, during the 10-hour period at an average temperature of 22.14 ± 1.48°C. * MP: Mobile phase; ** D: Diluent.
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