Crystalline drug, solubility

McFarland, J. W. Du, C. M. Avdeef, A., Factors influencing the water solubility of crystalline drugs, in van de Waterbeemd, H. Lennemas, H. Artursson, P. (eds.), Drug Bioavailability. Estimation of Solubility, Permeability, Absorption and Bioavailability, Wiley-VCH, Weinheim, 2003 (in press). 

Factors Influencing the Water Solubilities of Crystalline Drugs... 

We report here studies conducted with 58 crystalline drug-like compounds. The solubilities are of high quality, having been determined in only three laboratories using the same automated potentiometric method. However, the set is too small to... 

Figure 13. Screw extruders extrude poorly when the proportion of water soluble compounds, such as mannitol or lactose, reaches 50% or higher. Such formulations are better extruded with low-shear basket extruders (28). As the solubility increases from 5% to 30%, the percent of water needed for extrusion could decrease by up to 25%. This has implications for scale-up, as early lots of drug substance may have a different crystallinity or solubility profile than pilot lots.

Nevertheless, since almost all drug compounds are solid at ambient temperature, the calculation of aqueous drug solubility requires knowledge of the chemical potential, Acrystalline state. However, at present, there is no computational method available to reliably predict this chemical potential. Such prediction would involve knowledge about the crystal structure of the compound, which must... 

Molar Volume and Solubility Parameters for Some Liquid Compounds and Crystalline Drug Compounds... 

Selection of a stable crystalline drug form that usually exhibits lower solubility in water. The crystalline form that is physically most stable usually has the highest melting point. 

McFarland JW, Du CM, Avdeef A. Factors Influencing the water solubilities of crystalline drugs. Methods and Principles in Medicinal Chemistry 2003 55 1 163-1 183,... 

For solid dosage forms, the solubility, efficacy, and stability of a drug may depend on the particular crystalline state of the drug. Many crystalline drugs can exist in different crystalline states called polymorphs. It is expected that characterization of the solid dosage forms include not only the chemical identity but the polymorphic... 

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