Abstract
A microscopic mass balance approach has shown that the initial saturation (Is), absorption number (An), dose number (Do), and dissolution number (Dn) are four fundamental dimensionless parameters that can be used to estimate the fraction dose absorbed (F) of suspensions of poorly soluble drugs in humans. The dissolution number of a drug increases with decreasing its particle size. The effect of micronization onF for suspensions was investigated in terms ofDn. About 90% of maximalF can be achieved atDn≈2. Increasing the solubility of a drug results in better oral absorption through increasingDn and decreasingDo. The fractions dose absorbed of digoxin, griseofulvin, and benoxaprofen agree with predictedF values using estimated parameters. Drugs with lowDo and lowDn can be more completely absorbed by reducing particle size, while absorption of drugs with highDo and lowDn is limited by solubility and requires higher solubility to enhance the fraction dose absorbed in addition to micronization. Solubility at the physiological pH should be used for the estimation of the fraction dose absorbed.
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Oh, DM., Curl, R.L., Yong, CS. et al. Effect of micronization on the extent of drug absorption from suspensions in humans. Arch. Pharm. Res. 18, 427–433 (1995). https://doi.org/10.1007/BF02976347
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DOI: https://doi.org/10.1007/BF02976347