Cyclodextrins as pharmaceutical solubilizers.
Cyclodextrins are useful functional excipients that have enjoyed widespread attention and use. The basis for this popularity from a pharmaceutical standpoint, is the ability of these materials to interact with poorly water-soluble drugs and drug candidates resulting in an increase in their apparent water solubility. The mechanism for this solubilization is rooted in the ability of cyclodextrin to form non-covalent dynamic inclusion complexes in solution. Other solubilizing attribute may include the ability to form non-inclusion based complexes, the formation of aggregates and related domains and the ability of cyclodextrins to form and stabilize supersaturated drug solutions. The increase in solubility also can increase dissolution rate and thus improve the oral bioavailability of BCS Class II and IV materials. A number of cyclodextrin-based products have reached the market based on their ability to camouflage undesirable physicochemical properties. This review is intended to give a general background to the use of cyclodextrin as solubilizers as well as highlight kinetic and thermodynamic tools and parameters useful in the study of drug solubilization by cyclodextrins.
Brewster
Marcus E
ME
Chemical and Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. mbrewste@prdbe.jnj.com
Loftsson
Thorsteinn
T
D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods
D003505:Cyclodextrins; D005079:Excipients; D004364:Pharmaceutical Preparations; D012996:Solutions