Hydrophobic drugs bioavailability

X. Z. Qu et ah, Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biontacromolecules, 7(12), 3452-3459 (2006). 

It is well appreciated that dietary fat retards proximal gastrointestinal transit. For hydrophobic drugs with low aqueous solubility, dissolution becomes the rate-limiting process the appreciation that fat might increase bioavailability by increasing time available for dissolution and that mixed triglycerides often provide a better solvent than aqueous media has not been lost on formulation scientists. 

Liversidge, G. G and K. C. Cundy (1995). Particle size reduction for improvement of oral bioavailability of hydrophobic drugs I. Absolute bioavailability of nanocrystalline danazol in beagle takbgii.Pharm., 125 91-97. 

Schwarz, J., Lee, M., Weisspapir, M., Zhang, Q., and Lu, W. Increased bioavailability of coenzyme Q-10 in self-emulsifying controlled release tablet New type of delivery system for hydrophobic drugs. Int. Symp. Contr. Rel. Bioact. Mater. 28 824—825, 2001. 

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. This results in the enhancement of drug bioavailability by improving aqueous solubility and the physical and chemical stability of the drug, masking undesired side effects such as irritation, taste, or odor, and overcoming compatibility problems or interactions between drugs and excipients. 

Fig. 2 Comparison of dissolution (A) and bioavailability (B) of capsules containing a high dose hydrophobic drug. Key , fresh capsule A, capsules stored for 11 mo at room temperature. The plot shows that while dissolution is affected on prolonged storage, there is no corresponding change in bioavailability profiles. (From Ref p. 16, by courtesy of Wiley-Liss Inc., a subsidary of John Wiley Sons Inc.)...

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and oral bioavailability, of a range of hydrophobic drugs (77-80), however, commercialization has been limited because of... 

In the context of drug-like substances, hydrophobicity is related to absorption, bioavailability, hydrophobic drug-receptor interactions, metabolism and toxicity. Closely related to log P is the octanol-water distribution coefficient (logDpn), accounting for partition of pH-dependent mixture of ionizable species. Ionization of any compound makes it more water soluble and then less lipophilic. The log D can be calculated from log Pand acid dissociation constant pJC, by the following expression [Cronin, Aptula et al, 2002b Livingstone, 2003] ... 

Upld Technologies. It has been known for a long time that lipid-based formulations can significantly improve the bioavailability of hydrophobic drugs by facilitating drug dissolution, dispersion, and solubilization, either... 

Lipid suspensions are also known to enhance the bioavailability of hydrophobic drugs. Unlike lipid solutions, suspended drug needs to undergo additional dissolution before the absorption. Therefore, factors such as drug particle size and amount suspended may also influence the bioavailability. 

Frenkel, Y.V. et al. Concentration and pH dependent aggregation of hydrophobic drug molecules and relevance to oral bioavailability. J. Med. Chem. 2005, 48, 1974-1983. 

Drug molecules have to be dissolved in the GI tract to be absorbed. Poor aqueous solubility of hydrophobic drugs, which usually results in low bioavailability, has been one of... 

This inclusion in cyclodextrin leads to changes in the physicochemical properties of guest molecules, and can eventually have considerable therapeutic potential by improving its aqueous solubility, dissolution, stability and hence the bioavailability of guest molecule (hydrophobic drugs). Using this inclusion complexation technique, drugs with poor aqueous solubility can be formulated as nasal sprays, parenteral solutions, eye drops, etc. 

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