Cyclodextrins in Parenteral Formulations

Most drugs have very limited solubility in water and some can be extremely difficult to formulate as parenteral solutions where the dose should preferably be dissolved in couple of ml of aqueous media without use of organic solvents and surface active agents, or application of somewhat extreme techniques such as prodrug formation. Thus, pharmaceutical formulators are constantly looking for new, biologically acceptable, and low-cost armamentarium for parenteral formulation development. Cyclodextrins (CDs) are enabling pharmaceutical excipients that can temporarily camouflage undesirable physiochemical drug properties such as low aqueous solubility through formation of drug/CD inclusion complexes. CDs are cyclic oligosaccharides that have similar physiological and biological properties like linear saccharides of comparable molecular weight. Due to their very favorable toxicological and pharmacokinetic profiles their usage in parenteral drug formulations is frequently preferred over other solubilizing techniques. Here the physiochemical and biological properties of CDs are reviewed as well as their pharmacokinetics after intravenous administration. Their regulatory status is briefly reviewed and their tendency to self-assemble to form clusters or aggregates discussed. Finally, some examples are given of how CDs are applied in aqueous parenteral formulations, how their solubilizing effect has been enhanced and how their target concentration is determined.