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DDS_Drug-Like Properties_09 - I.Solubility...

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Drug Like Molecular Properties I. Solubility Drugs must be in solution to be absorbed Dose (mg/kg) High Permeability Med Permeability Low Permeability 0.1 1 5 ~20 1 10 ~50 ~200 10 100 ~500 ~2000 Desired Solubility (μg/mL) for Anticipated Dose
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Estimating Solubility of Unionized Compounds (Lemke Method)
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Estimating Solubility Log PC > 0.5 poor aqueous solubility Log S w = -0.01(MP) – log PC +1.05 Where S w = water solubility, MP = melting point, PC = partition coefficient Quantitative Structure Activity Relationships Group Contributions Molecular Surface Area Comparative Molecular Field Analysis (CoMFA) Linear Solvation Energy
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Measuring Solubility Equilibrium Solubility Place “excess” solid drug in a known quantity of aqueous medium (known pH, ionic strength). Gently mix (24 48 hr). Remove an aliquot of suspension, filter, and analyze for drug content. Limitations requires a “large” amount of compound ? Drug stability during equilibration period unknown losses to filter requires an analytical method for quantification
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