title: The use of chemically modified cyclodextrins in the development of formulations for chemical delivery systems.
abstract: Retrometabolic drug design provides a highly useful and directed approach for identifying new drug candidates with improved therapeutic indices based on predictable/controlled metabolism and/or site-targeted delivery. In the process, formulation becomes an important and integral concern especially for brain-targeting chemical delivery systems (CDS) based on the need for appropriate dosage form stability, solubility and dissolution characteristics. Adjuncts that have been useful in this regard are chemically modified, water soluble cyclodextrin derivatives such a 2-hydroxypropyl-beta-cyclodextrin (HP beta CD). These starch-derived excipients can interact with drugs via dynamic complex formation resulting in a number of beneficial pharmaceutical effects including increased apparent water solubility and stability as well as improved aesthetic and excipient compatibility properties. This cyclodextrin is approved in a number of product in the US and world-wide. HP beta CD has contributed to the development and preclinical/clinical testing of a number of CDS including E2 (estradiol)-CDS, AZT (zidovudine)-CDS, DEX (dexamethasone)-CDS and a neuropeptide CDS based on an enkephalin derivative. In these contexts, HP beta CD provided for stable and water-soluble dosage forms intended for parenteral administration.
authors.affiliation: Department of Drug Delivery Research, Division of Chem-Pharm Drug Evaluation, Janssen Research Foundation, Beerse, Belgium. mbrewste@janbe.jnj.com
authors.forename: M E
authors.initials: ME
authors.lastname: Brewster
authors.forename: T
authors.initials: T
authors.lastname: Loftsson
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D006801:Humans
chemical_list: D003505:Cyclodextrins; D005079:Excipients