Design and Evaluation of Cyclodextrin-Based Drug Formulation

Kaneto Uekama
2004 Chemical and pharmaceutical bulletin  
Introduction Cyclodextrins (CyDs) were first isolated in 1891 as degradation products of starch and were characterized as cyclic oligosaccharides. 1) The a-, b-, and g-CyDs are the most common natural CyDs, consisting of six, seven, and eight glucose units, respectively (Fig. 1) . 2) Recently, various kinds of CyD derivatives such as hydrophilic, hydrophobic and ionic derivatives have been developed to extend physicochemical properties and inclusion capacity of natural CyDs. [3] [4] [5] [6] [7]
more » ... [8] [9] [10] They are applicable as a functional drug carrier to control the rate and/or time profile of drug release. [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] Hydrophilic CyDs can modify the release rate of poorly water-soluble drugs, which can be used for the enhancement of drug absorption across biological barriers, serving a potent drug carrier in the immediate release formulations. 15, 19, [21] [22] [23] [24] Amorphous CyDs such as 2-hydroxypropyl-b-CyD (HP-b-CyD) are useful for inhibition of polymorphic transition and crystallization rates of poorly water-soluble drugs during storage, which can consequently maintain the higher dissolution characteristics and oral bioavailability of the drugs. 25-32) On the other hand, hydrophobic CyDs may serve as sustained release carriers for the water-soluble drugs 33-38) including peptide and protein drugs. 39, 40) The delayed release formulation can be obtained by the use of enteric type CyDs such as Ocarboxymethyl-O-ethyl-b-CyD. 41,42) A combined use of different CyDs and/or pharmaceutical additives will provide more balanced oral bioavailability with prolonged therapeutic effects. [43] [44] [45] [46] The most desirable attribute for the drug carrier is its ability to deliver a drug to targeted site. The CyD/drug conjugate can survive passage through stomach and small intestine, but the drug release will be triggered by enzymatic degradation of CyD ring in colon. 47-56) Such CyD conjugate can be a versatile means of constructing a new class of colon-targeting prodrug. Moreover, CyD/cationic polymer conjugates may be novel candidates for non-viral vectors to enhance the gene transfer of plasmid DNA. 57-59) On the basis of the above-mentioned knowledge, the advantages and limitations of CyDs in the design of advanced dosage forms will be discussed. 900 The pharmaceutically useful cyclodextrins (CyDs) are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in design and evaluation of CyDbased drug formulation, focusing on their ability to enhance the drug absorption across biological barriers, the ability to control the rate and time profiles of drug release, and the ability to deliver a drug to a targeted site.
doi:10.1248/cpb.52.900 pmid:15304981 fatcat:4jnx5gnchzadvbmtvhtew4oqcm