Bioavailability pharmaceutical cyclodextrins

A good deal of attention recently has been directed towards the use of derivatives of cyclodextrin for the solubilization and stabilization of pharmaceuticals [124 126]. One cautionary note—complexation may adversely affect the dissolution an/or permeability characteristics of the drug, thereby possibly decreasing drug bioavailability. 

Part II starts with the possibilities of ACE for characterizing the relevant physicochemical properties of drugs such as lipophilicity/hydrophilicity as well as thermodynamic parameters such as enthalpy of solubilization. This part also characterizes interactions between pharmaceutical excipients such as amphiphilic substances (below CMC) and cyclodextrins, which are of interest for influencing the bioavailability of drugs from pharmaceutical formulations. The same holds for interactions of drugs with pharmaceutical vehicle systems such as micelles, microemulsions, and liposomes. 

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. 

Complexation is one of several ways to favorably enhance the physicochemical properties of pharmaceutical compounds. It may loosely be defined as the reversible association of a substrate and ligand to form a new species. Although the classification of complexes is somewhat arbitrary, the differentiation is usually based on the types of interactions and species involved, e.g., metal complexes, molecular complexes, inclusion complexes, and ion-exchange compounds. Cyclodextrins (CDs) are classic examples of compounds that form inclusion complexes. These complexes are formed when a guest molecule is partially or fully included inside a host molecule e.g., CD with no covalent bonding. When inclusion complexes are formed, the physicochemical parameters of the guest molecule are disguised or altered and improvements in the molecule s solubility, stability, taste, safety, bioavailability, etc., are commonly seen. 

Ghorab, M.K. Effect of wet granulation of ibuprofen and P-cyclodextrin on complexation, dissolution and bioavailability. Ph.D. diss., Graduate School of Pharmaceutical Sciences, Duquesne University, 2001, p. 7. 

The ever-increasing demands on the performance of pharmaceutical formulations with respect to, e.g., storage stability, increased dosage levels, greater bioavailability, fewer side effects, controlled release, and biological response (e.g., tissue distribution) constitute the main motivation for drug delivery research. In the last few decades, this research has resulted in the development of, e.g., parenteral emulsions, liposomes with improved circulation in the bloodstream, cyclodextrins, and lipoprotein mimics for cancer therapeutics. 

ABSTRACT. Cyclodextrins are applied to facilitate formulation problems, to improve stability and bioavailability Following factors are determining whether or not cyclodextrins can be applied in oral pharmaceutical preparations ... 

However, its low solubility and chemical instability in water have limited the dosage form design and presented a substantial challenge to pharmaceutical scientists (3). Cyclodextrins (CyDs) have been successfully applied to improve the pharmaceutical properties of various drugs (4,5,6). In our preliminary study, it was found that HCFU forms solid complexes with a-, 3 and yCyDs. Thus, the present study dealt with the inclusion complexation of HCFU with three CyDs in an attempt to obtain improved solubility, dissolution rate, chemical stability, and bioavailability of HCFU. 

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