Functional substrates for the gradual release of agents

This work describes the functionalization of a natural and a man-made textile substrate, namely cotton and polyamide 6.6, with inclusion agents, β-cyclodextrins (β-CDs) that are able to release gradually to the user active ingredients. In this study we used aescin (aesculus hippocastanum extract), which is a natural agent with benefits for the treatment of varicose veins.¹H NMR and UV–vis data supported the role of β-CDs as an aescin complexing agent, and the covalent nature of the linkage between β-cyclodextrins and the textile substrates, which showed a wash fastness to more than 45 washing cycles.     

超分子化学与环糊精

超分子化学是上世纪八十年代末兴起的一门新兴边缘学科,它的发展为各个学科的研究和新技术、新材料的研发开拓了一个崭新的领域。环糊精是超分子化学的重要研究内容之一。本文对环糊精的来源和分子结构特点作了简单介绍,论述了环糊精及其衍生物任超分子化学领域中的地位和作用,显示出超分子化学及环糊精研究和应用的无限潜力。     

Macromolecular recognition by cyclodextrins. Interaction of cyclodextrins with polymethacrylamides bearing hydrophobic amino acid residues

The interaction of cyclodextrins (CDs) with poly(N-methacryloyltryptophan) (pMTrp) and with poly(N-methacryloylphenylalanine) (pMPhe) was investigated as a simple model system of macromolecular recognition of proteins. The association constants (K) for the model compounds, sodium salts of tryptophan and phenylalanine, are not so different (i.e. 43 and 16 M⁻¹ for α-CD, 59 and 69 M⁻¹ for β-CD, and 12 and 3 M⁻¹ for γ-CD, respectively). On the other hand, there is a significant difference in the apparent K values for pMTrp and pMPhe (i.e. the K values for pMPhe are considerably smaller than ca. 10 M⁻¹, whereas those for pMTrp are 30, 83, and 11 M⁻¹ for α-, β-, and γ-CDs, respectively). These observations indicate that a subtle difference in polymer side chains can be critical in macromolecular recognition.     

Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes

The aim of this study was to investigate the usefulness of combined application of quality by design tools such as central composite design (CCD), response surface methodology (RSM), and artificial neural networks (ANN) in the characterization, modeling, and optimizaton of spray drying of a poorly soluble drug : cyclodextrin complex. Models were developed by RSM and ANN from different pools of data. The model with best predictability was the ANN multilayer perceptron (MLP)1 model developed from the largest group of data (R ² for response yield 0.854, moisture content 0.886). On the other hand, analysis of equations derived from the application of RSM contributed in better understanding the complex relationships between input and output variables. By application of a desirability function approach, optimal process parameters that resulted in the best process yield (86%) and minimal moisture content in the powder (3.3%) were established (25% feed concentration, 180°C inlet air temperature, 10% pump speed).     

Multicomponent complexes of piroxicam with cyclodextrins and hydroxypropyl methylcellulose

The purpose of the study was to investigate the effect of hydroxypropyl methylcellulose (HPMC) on the complexation of piroxicam (PX) with β-cyclodextrin (β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) in solution and in the solid state. Phase solubility study revealed a positive effect of the polymer on the drug complexation. Improvement in stability constants values, K_s, of ternary complexes clearly proves the benefit of the HPMC addition for promoting higher complexation efficiency. Solid binary and ternary complexes were prepared by spray drying. Drug-CD and drug-CD-polymer interactions were studied in the solid state by differential scanning calorimetry (DSC), zeta-potential measurements, and particle size distribution. A marked increase in the PX dissolution rate was observed even in binary and ternary complexes. The presence of HPMC in ternary complexes slightly retarded the release of PX. Cyclodextrin complexation increased the PX concentration gradient over the semipermeable membrane, resulting in an increased PX flux. The retarded diffusion of PX to the membrane interface decreased the PX flux values of the ternary complexes.     

Investigation of the piroxicam/hydroxypropyl-β-cyclodextrin inclusion complexation by means of a supercritical solvent in the presence of auxiliary agents

The complexation of piroxicam and 2-hydroxypropyl-β-cyclodextrin by means of supercritical CO₂ has been investigated. The experiments were carried out by varying the temperature, pressure and contact time and introducing two different auxiliary agents: polyvinyl pyrrolidone or l-lysine.Cyclodextrins, which are widely used to solubilize a large variety of poorly soluble drugs, are often used in combination with some auxiliary agents to enhance the complexation efficiency of the conventional techniques. While many recent literature works report that supercritical carbon dioxide is a clean, non-toxic alternative to organic solvents, the use of auxiliary agents in the supercritical complexation process has been scarcely examined and still needs to be investigated.The inclusion complexes obtained in this work were analysed by means of the ‘differential solubility method’, differential scanning calorimetry and Fourier transform infrared spectroscopy. The results showed that the supercritical treatment could be successfully employed below 140-150 °C without incurring thermal degradation of the samples. While 66% inclusion efficiency could be obtained at 140 °C and 30 MPa for a mixture of piroxicam/2-hydroxypropyl-β-cyclodextrin (1:2 molar ratio), higher percentages of complexation (95% in the ternary samples with polyvinyl pyrrolidone and 89-91% in those with l-lysine) could be obtained at a lower temperature (130 °C) when auxiliary agents were employed.     

Synthesis and characterization of biodegradable hydrogels based on photopolymerizable acrylate-terminated CL-PEG-CL macromers with supramolecular assemblies of α-cyclodextrins

A series of polypseudorotaxanes were synthesized from α-cyclodextrins (α-CDs) threaded onto photopolymerizable CL-PEG-CL oligomers bearing acrylate terminals. The corresponding supramolecular structured hydrogels were prepared from these polypseudorotaxanes in a mixed solvent of H₂O and DMSO via in situ photopolymerization under UV irradiation. The structure and properties of the gels were characterized by FTIR, TGA-DTG and WAXD. The results show that α-CDs are threaded and immobilized onto the network chains of the hydrogel with crosslinking junctions as stoppers topologically, and the feed molar ratio of α-CDs to the macromers affects the hydrogel structure and the water distribution in the hydrogel. These supramolecular structured hydrogels may be good candidates for biomaterial applications.     

Solubility and dissolution rate of progesterone-cyclodextrin-polymer systems

This contribution focused on the solubility improvement of the poorly water-soluble steroid hormone progesterone which, in its natural state, presents a reduced oral bioavailability. In the first part of this study, two simple, reproducible methods that were candidates for use in the preparation of inclusion complexes with cyclodextrins were investigated. Solubility capacities of the progesterone complex with hydroxypropyl-β-CD (HPβ-CD), hydoxypropyl-γ-CD (HPγ-CD), permethyl-β-CD (PMβ-CD), and sulfobutylether-β-CD (SBEβ-CD), prepared by the freeze-drying and precipitation methods, were evaluated by Higuchi phase solubility studies. The results showed that HPβ-CD and PMβ-CD were the most efficient among the four cyclodextrins for the solubilization of progesterone, with the highest apparent stability constants. Therefore, dissolution studies were conducted on these latest progesterone/cyclodextrin complexes and physical mixtures. Two additional natural cyclodextrins, β-CD and γ-CD, were taken as references. Hence, the influence of more highly soluble derivatives of β-CD (HPβ-CD, PMβ-CD) on the progesterone dissolution rate, in comparison to pristine β-CD, alongside an increase in the cavity width for γ-CD versus β-CD, were investigated. The dissolution kinetics of progesterone dissolved from HPβ-CD, PMβ-CD, and γ-CD revealed higher constant rates in comparison to β-CD. Therefore, the aim of the second part of this study was to investigate the possibility of improving the dissolution rate of progesterone/β-CD binary systems upon formation of ternary complexes with the hydrophilic polymer, PEG 6000, as β-CD had the smallest progesterone solubility and dissolution capacity among the four cyclodextrins studied (β-CD, HPβ-CD, HPγ-CD and PMβ-CD). The results indicated that dissolution constant rates were considerably enhanced for the 5% and 10% progesterone/β-CD complexes in PEG 6000.

The interaction of progesterone with the cyclodextrins of interest on the form of the binary physical mixtures, complexes, or ternary complexes were investigated by differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR). The results proved that progesterone was diffused into the cyclodextrin cavity, replacing the water molecules and, in case of ternary systems, that the progesterone β-cyclodextrin was well dispersed into PEG, thus improving progesterone bioavailability for subsequent oral delivery in the same way as derivatized cyclodextrins. The present work proves that ternary complexes are promising systems for drug encapsulation.