Purpose Currently, the FDA allows biowaivers for Class I\n(high solubility and high permeability) and Class III (high solubility\nand low permeability) compounds of the\nBiopharmaceutics Classification System (BCS). Scientific evidence\nshould be provided to support biowaivers for BCS Class\nI and Class III (high solubility and low permeability)\ncompounds.\nMethods Data on the effects of excipients on drug permeability\nare needed to demonstrate that commonly used excipients\ndo not affect the permeability of BCS Class III compounds,\nwhich would support the application of biowaivers to Class III\ncompounds. This study was designed to generate such data by\nassessing the permeability of four BCS Class III compounds\nand one Class I compound in the presence and absence of five\ncommonly used excipients.\nResults The permeability of each of the compounds was\nassessed, at three to five concentrations, with each excipient\nin two different models: Caco-2 cell monolayers, and in situ rat\nintestinal perfusion. No substantial increases in the permeability\nof any of the compounds were observed in the presence of\nany of the tested excipients in either of the models, with the\nexception of disruption of Caco-2 cell monolayer integrity by\nsodium lauryl sulfate at 0.1 mg/ml and higher.\nConclusion The results suggest that the absorption of these\nfour BCS Class III compounds would not be greatly affected\nby the tested excipients. This may have implications in\nsupporting biowaivers for BCS Class III compounds in\ngeneral.
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