Cyclodextrins as Functional Excipients: Methods to Enhance Complexation Efficiency

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 9; pp. 3019 - 3032
• Main Authors: Loftsson, Thorsteinn, Brewster, Marcus E.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Biological and medical sciences; Chemistry, Pharmaceutical; complex; complexation efficiency; cyclodextrin; Cyclodextrins - chemistry; dissolution; Drug Carriers; Excipients - chemistry; General pharmacology; inclusion compounds; Medical sciences; Models, Chemical; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; preformulation; Solubility; solubilization; Technology, Pharmaceutical - methods; complexation efficiency; solubilization; cyclodextrin; complex; dissolution; solubility; inclusion compounds; preformulation; Complexation; Pharmaceutical technology; Vehicle(excipient); Solubility; Solubilization; Dissolution; Cyclodextrin; Efficiency; Oside polymer; Inclusion compound; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23077

Cyclodextrins have gained currency as useful solubilizing excipients with an ever increasing list of beneficial properties and functionalities. Although their use in liquid dosage forms including oral and parenteral solutions is straightforward, their application to solids can be confounded by the added bulk that is contributed to the formulation. This factor has limited the use of cyclodextrin in tablets and relates systems mainly to potent drug substances. Increasing the ability of cyclodextrins to complex with drug through a manipulation of their complexation efficiency (CE) may expand the use of these materials to the increasing list of drug candidates and marketed drugs who may benefit from this technology. This brief review assesses tools and materials that have been suggested for increasing the CE for pharmaceutically useful cyclodextrins and drugs. The relative importance of impacting the drug solubility (S0) and phase-solubility isotherm slope is discussed in the context of drug ionization and salt use; the impact of polymers, charge interactions, and charge shielding; and the coincidental formation of other complex types in the media. The influence of drug form as well as supersaturation is also discussed in the context of the responsible mechanisms along with aggregation, inclusion, and noninclusion complex formation.