Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharides that emerged as industrial excipients in the early 1970s and are currently found in at least 130 marketed pharmaceutical products, in addition to numerous other consumer products. Although CDs have been the subject of close to 100,000 publications since their discovery, and although their structure and properties appear to be trivial, CDs are constantly surprising investigators by their unique physicochemical properties. In aqueous solutions, CDs are solubilizing complexing agents of poorly soluble drugs while they can also act as organic cosolvents like ethanol. CDs and their complexes self-assemble in aqueous solutions to form both nano- and microparticles. The nanoparticles have diameters that are well below the wavelength of visible light; thus, the solutions appear to be clear. However, the nanoparticles can result in erroneous conclusions and misinterpretations of experimental results. CDs can act as penetration enhancers, increasing drug permeation through lipophilic membranes, but they do so without affecting the membrane barrier. This review is an account of some of the unexpected results the authors have encountered during their studies of CDs as pharmaceutical excipients.

Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine

“…Our value of the CAC of pure SBE-β-CD appeared to be the same as it was reported by Loftsson et al [ 43 ]. As follows from Table 1 , CBZ did not influence the CAC of cyclodextrin (the values were within the experimental error).…”

Characterization, Preparation, and Promotion of Plant Growth of 1,3-Diphenylurea/β-Cyclodextrin Derivatives Inclusion Complexes

“…The phase-solubility diagrams are a generalized method also based on the method of Higuchi and Connors et al for predicting the complex formation of CDs and drugs in solution. , Phase-solubility diagrams were prepared based on the solubility changes of the βCD/DPU and HP-βCD/DPU inclusion complexes in solution to calculate stability constants and to predict inclusion molar ratios (Figure ). The solubility diagram is classified into two types: type A (soluble complex) and type B (insoluble complex), with type A represented by A L (linear diagram), A P (positive deviation from linearity), and A N (negative deviation from linearity) and type B by B S (the complex has limited solubility) and B I (the complex is insoluble) .…”

“… 28 Therefore, the inclusion molar ratios of βCD/DPU = 1/1 and HP-βCD/DPU = 1/2 in the solution state are presumed to be βCD/DPU = 1/1 and HP-βCD/DPU = 1/2, respectively. The stability constants ( K s ) and complexation efficiencies (CEs) of βCD/DPU and HP-βCD/DPU were calculated using the method described by Higuchi et al 26 The K s and CEs of βCD/DPU were found to be K 1/1 = 250 M –1 , CE = 2.48× 10 –3 . The K s and CEs of HP-βCD/DPU were found to be K 1/1 = 427 M –1 , CE = 3.93 × 10 –3 and K 2/1 = 196 M –1 , CE = 1.93 × 10 –3 respectively.…”

Encapsulation of Fennel and Basil Essential Oils in β-Cyclodextrin for Novel Biopesticide Formulation

“…The recorded micrographs showed tiny aggregates of particles with lamellate morphology, with no fractures on the surface texture. The detected aggregates can be classified by size as stable microparticles that can precipitate from aqueous media but disassemble upon medium dilution [ 72 ]. The particles were similar to the IC of β-CD containing curcumin, lemongrass oil, geranium oil, eucalyptus oil, clove oil, and oregano oil [ 73 , 74 , 75 ].…”