Preparation and Evaluation of Inclusion Complexes of Commercial Sunscreens in Cyclodextrins and Montmorillonites: Performance and Substantivity Studies

Herein we describe inclusion complexes of commercial sunscreens in cyclodextrins and montmorillonites to generate new sunscreen derivatives with optimized functional properties such as water resistance and skin adherence. Four cyclodextrins (α-, β-, and γ-cyclodextrin, and β-dimethyl cyclodextrin) and two montmorillonites (sodium and alkylammonium) were investigated for encapsulating some commercial sunscreens. Our results reveal a good yield and inclusion products with functional properties obtained by using kneading technique on Eusolex® 2292 and Eusolex® 6007 in β-cyclodextrin and solubilization method on Eusolex® 6007 and NeoHeliopan® MA in montmorillonite. In addition, molecular modeling studies indicated flexibility as important for the intercalation of the host molecule.     

Analytical study of photodegradation of inclusion complexes of nimodipine with alpha-, gamma-cyclodextrin, methyl-beta-cyclodextrin, and hydroxypropyl-beta-Cyclodextrin

The inclusion behavior of alpha-cyclodextrin (alpha-CD), gamma-cyclodextrin (gamma-CD), hydroxypropyl-beta-cyclodextrin (HP-betaCD), and methyl-beta-cyclodextrin (M-betaCD) with nimodipine (NM) in solution and in the solid state was investigated. Inclusion complexes of nimodipine with cyclodextrins (at a molar ratio of 1:1) in the solid state were obtained by the kneading method. Photochemical stability of NM in the solid inclusion complexes was assessed by IR spectrometry. The modified derivatives of beta-CD and alpha-CD were found to slow the photodegradation rate, whereas in the presence of gamma-CD the photodegradation of NM was a bit faster than in the corresponding physical mixture. Photochemical degradation of NM in liquid inclusion complexes was monitored by UV spectroscopy. According to the slowing effect on photodegradation of NM in the inclusion complexes, the studied cyclodextrins can be ordered as gamma-CD < alpha-CD < HP-betaCD < M-betaCD.     

蒙脱土有机改性对丁基橡胶复合材料微观结构与性能的影响

采用季铵盐有机改性蒙脱土(OMMT)与丁基橡胶(IIR)机械共混和硫化制备成复合材料。研究了蒙脱土有机改性前后对复合材料的微观结构、力学和芥子气防护性能的影响。透射电镜(TEM)和X射线衍射(XRD)显示IIR/OMMT复合材料为插层型纳米复合材料,而IIR/MMT为未插层的微米复合材料。复合材料的微观结构和填料的界面活性对其力学性能影响重大,IIR/OMMT复合材料的力学性能明显优于IIR/MMT复合材料的力学性能。添加有机或无机蒙脱土都可使芥子气在丁基橡胶中的扩散系数显著降低。而芥子气在IIR/OMMT中的扩散系数更低,这显示出IIR/OMMT复合材料的芥子气防护性能更加优异。     

Pharmaceutical Uses of Cyclodextrins and Derivatives

Due to their particular conformation, cyclodextrins have the remarkable characteristic of being able to include various kinds of molecule inside their hydrophobic cavity, conferring on them an environmental hydrophily. These inclusion compounds have completely new pharmacotechnical properties, but the most important ones concern increases in water solubility and bioavailability. When administered orally, the inclusion compounds decompose, allowing the free active ingredient to be absorbed by the gastro-intestinal mucosa. However, a certain proportion of inclusion compound is absorbed without any dissociation.

Some cyclodextrin derivatives are very interesting because of their very high water solubility, and also because of their low parenteral toxicity compared with the original β-cyclodextrin. However, in parenteral administration, it is absolutely necessary to study the pharmacokinetic and pharmacological characteristics of the inclusion compound, which must be considered as the true active ingredient.     

Influence of cyclodextrin complexation on the in vivo photoprotective effects of oxybenzone

The objective of the current study was to investigate the influence of cyclodextrin complexation on the in vivo photoprotective effects of a model ultraviolet (UV) absorber, oxybenzone, and to compare these novel sunscreens to a commercial SPF 30 sunscreen product. Aqueous-based solutions and suspensions containing 2.7 mg/mL oxybenzone and up to 20% (w/w) hydroxypropyl-β-cyclodextrin (HPCD) were prepared. The sunscreens were applied to the dorsal skin of SKH-1 hairless mice and the animals were exposed to up to two minimal erythemal doses (MEDs) of UV radiation. Control animals received no sunscreen treatment. Lipid damage, as quantified by decreases in the lipid melting temperature of the epidermis, was determined using differential scanning calorimetry immediately after UV exposure. The number of sunburn cells (SBCs) and the extent of edema were measured 24 hours postexposure. Results showed that all oxybenzone-containing formulations decreased the number of SBCs formed, diminished swelling, and reduced the physical damage to the skin structure, in comparison to control. Thus, complexation did not prevent oxybenzone from reacting with light. The 20% HPCD formulation exhibited more substantial photoprotection at UV exposures of one or two MEDs, as evidenced by the formation of fewer SBCs. The 5% HPCD formulation also provided substantial protection against epidermal lipid damage. These studies demonstrate that inclusion of HPCD in sunscreen formulations may enhance the in vivo photoprotective effects of the UV absorbers. No single HPCD-containing sunscreen, however, was found to be equivalent to a commercially available sunscreen product for all biomarkers investigated.     

Pharmaceutical Uses of Cyclodextrins and Derivatives

Abstract

Due to their particular conformation, cyclodextrins have the remarkable characteristic of being able to include various kinds of molecule inside their hydrophobic cavity, conferring on them an environmental hydrophily. These inclusion compounds have completely new pharmacotechnical properties, but the most important ones concern increases in water solubility and bioavailability. When administered orally, the inclusion compounds decompose, allowing the free active ingredient to be absorbed by the gastro-intestinal mucosa. However, a certain proportion of inclusion compound is absorbed without any dissociation.

Some cyclodextrin derivatives are very interesting because of their very high water solubility, and also because of their low parenteral toxicity compared with the original β-cyclodextrin. However, in parenteral administration, it is absolutely necessary to study the pharmacokinetic and pharmacological characteristics of the inclusion compound, which must be considered as the true active ingredient.     

Inclusion complexes of fluorofenidone with β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Background: Fluorofenidone is a novel antifibrotic drug and its aqueous solubility is low. Aim: This study was to prepare and characterize inclusion complexes of fluorofenidone (AKF-PD) with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Method: The AKF-PD/cyclodextrins (CDs) inclusion complexes were prepared by coprecipitation and freeze-drying, respectively. The solubility enhancement of AKF-PD was evaluated by phase solubility method. Inclusion complexation in solid phase was studied by X-ray diffraction (XRD) and differential thermal analysis (DTA). The dissolution profiles of AKF-PD/CDs inclusion complexes were investigated and compared with those of their physical mixtures and AKF-PD alone. Results: The phase solubility diagrams of AKF-PD with β-CD and HP-β-CD were of A_L-types, and the solubility of AKF-PD could be increased by 51.5% for β-CD at 0.014 M and 794.0% for HP-β-CD at 0.254 M. The results from XRD and DTA suggested that AKF-PD could form inclusion complex with β-CD or HP-β-CD. The dissolution rate of AKF-PD from the inclusion complexes was much more rapid than AKF-PD alone. Conclusions: The formulation of AKF-PD/CDs inclusion complexes showed superior performance in improving dissolution properties of AKF-PD.     

Solubility and Dissolution Rate of Progesterone-Cyclodextrin-Polymer Systems

ABSTRACT

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.     

Enhanced Aqueous Solubility of Phenolic Antioxidants Using Modified β-Cyclodextrins

Abstract

Phenolic antioxidants are useful additives with a possible role in cancer chemoprevention. This study describes inclusion complexation between phenolic antioxidants (butylated hydroxyanisole, BHA; butylated hydroxytoluene, BHT) and hydroxypropyl-β-cyclodextrins (HPB) or hydroxyethyl-β-cyclodextrin (HEB) and their characterization by phase solubility analysis, Xray diffraction and infrared (IR) spectroscopy. The complexes were prepared by shaking an aqueous mixture of the antioxidant with each of the cyclodextrins (1:1 molar) at 40 °C for six days and lyophilizing the resulting clear solution. Each of the complexes dissolved instantaneously in water. Phase solubility analysis indicated a more pronounced increase in the aqueous solubility of BHA compared to that of BHT. Xray diffraction patterns of the antioxidant-cyclodextrin complexes indicated a shift from crystalline pattern of the antioxidant to an amorphous pattern for the complexes. Also, the IR spectra of the BHA-cyclodextrin complexes indicated an almost complete disappearance or at least a shift in the -C-O-C- stretch (1200 cm^-1) compared to the corresponding stretch observed for BHA alone or a physical mixture (1:1) of BHA and each of the cyclodextrins. Furthermore, the sharp -OH absorption (3600 cm^-1) is retained in a physical mixture of BHT with either cyclodextrin (1:1) whereas this stretch is not observed in the IR spectra of either BHT-cyclodextrin complexes. These evidences indicate the formation of an inclusion complex between the antioxidants and each of the cyclodextrins.     

Enhanced Aqueous Solubility of Phenolic Antioxidants Using Modified β-Cyclodextrins

Phenolic antioxidants are useful additives with a possible role in cancer chemoprevention. This study describes inclusion complexation between phenolic antioxidants (butylated hydroxyanisole, BHA; butylated hydroxytoluene, BHT) and hydroxypropyl-β-cyclodextrins (HPB) or hydroxyethyl-β-cyclodextrin (HEB) and their characterization by phase solubility analysis, Xray diffraction and infrared (IR) spectroscopy. The complexes were prepared by shaking an aqueous mixture of the antioxidant with each of the cyclodextrins (1:1 molar) at 40 °C for six days and lyophilizing the resulting clear solution. Each of the complexes dissolved instantaneously in water. Phase solubility analysis indicated a more pronounced increase in the aqueous solubility of BHA compared to that of BHT. Xray diffraction patterns of the antioxidant-cyclodextrin complexes indicated a shift from crystalline pattern of the antioxidant to an amorphous pattern for the complexes. Also, the IR spectra of the BHA-cyclodextrin complexes indicated an almost complete disappearance or at least a shift in the -C-O-C- stretch (1200 cm^-1) compared to the corresponding stretch observed for BHA alone or a physical mixture (1:1) of BHA and each of the cyclodextrins. Furthermore, the sharp -OH absorption (3600 cm^-1) is retained in a physical mixture of BHT with either cyclodextrin (1:1) whereas this stretch is not observed in the IR spectra of either BHT-cyclodextrin complexes. These evidences indicate the formation of an inclusion complex between the antioxidants and each of the cyclodextrins.     

Effects of Grinding with Microcrystalline Cellulose and Cyclodextrins on the Ketoprofen Physicochemical Properties

Ground mixtures of ketoprofen (KETO) with native crystalline β-cyclodextrin, amorphous statistically substituted methyl-β-cyclodextrin, and microcrystalline cellulose were investigated for both solid phase characterization (differential scanning calorimetry (DSC) powder X-ray diffractometry, and infrared (IR) spectrometry) and dissolution properties (dispersed amount and rotating disk methods) to evaluate the role of the carrier on the performance of the final product. The effects of different grinding conditions, partial sample dehydration, and 1 year storage at room temperature were also investigated. The results pointed out the importance of the carrier nature on the efficiency of the cogrinding process. Both cyclodextrins were much more effective than was microcrystalline cellulose, even though no true inclusion complex formation occurred by mechanochemical activation. The best results were obtained from ground mixtures with methyl-β-cyclodextrin, which showed the best amorphizing and solubilizing power toward the drug and permitted an increase of approximately 100 times its intrinsic dissolution rate constant, in comparison with the approximate 10 times increase obtained from ground mixtures with β-cyclodextrin.     

Cyclodextrins,Their Value in Pharmaceutical Technology

Cyclodextrins are cyclic oligosaccharides consisting of a variable number of glucose units (usually 6 to 81. The ring formed by cyclodextrins is externally very hydrophilic and relatively apolar internally. In liquid or solid medium, these molecules are capable of forming inclusion compounds with many other molecules. The inclusion compounds thus formed display interesting properties in comparison with the starting molecule.

In fact, inclusion may increase the stability of the guest molecules. Greater stability may be shown towards heat, resulting in lower volatility or higher thermal resistance. Greater stability may also be oxidation resistance. It may also concern the products in solution, whose hydrolysis may, in certain cases, be inhibited to varying degrees. For relatively insoluble active ingredients, inclusion may improve the solubility or dissolution rate. Depending on the stability constant of the inclusion compound formed, a better passage of the active ingredient through membranes may be observed. In vivo, this may be reflected by an increase in bioavailability, with a simultaneous increase in therapeutic effectiveness.     

Examination of ionic liquids and their interaction with molecules, when used as stationary phases in gas chromatography.

Stable room-temperature ionic liquids (RTILs) have been used as novel reaction solvents. They can solubilize complex polar molecules such as cyclodextrins and glycopeptides. Their wetting ability and viscosity allow them to be coated onto fused silica capillaries. Thus, 1-butyl-3-methylimidazolium hexafluorophosphate and the analogous chloride salt can be used as stationary phases for gas chromatography (GC). Using inverse GC, one can examine the nature of these ionic liquids via their interactions with a variety of compounds. The Rohrschneider-McReynolds constants were determined for both ionic liquids and a popular commercial polysiloxane stationary phase. Ionic liquid stationary phases seem to have a dual nature. They appear to act as a low-polarity stationary phase to nonpolar compounds. However, molecules with strong proton donor groups, in particular, are tenaciously retained. The nature of the anion can have a significant effect on both the solubilizing ability and the selectivity of ionic liquid stationary phases. It appears that the unusual properties of ionic liquids could make them beneficial in many areas of separation science.     

Physicochemical properties of organoclay filled polylactic acid/natural rubber blend bionanocomposites

A novel toughened polylactic acid (PLA) bionanocomposite with tuneable properties was successfully prepared by melt mixing PLA with natural rubber and several montmorillonites (MMTs). The organoclays were preferentially located at the interface acting as compatibilisers between both polymer phases. This location resulted in a marked improvement of the physical and mechanical properties of the system. Moreover, these properties can be controlled as a function of the nanofiller nature and the mixing procedure used.     

Characterization of sodium dodecyl sulfate modified iron pillared montmorillonite and its application for the removal of aqueous Cu(II) and Co(II)

Anionic surfactant modified Fe-pillared montmorillonites were prepared by Fe-hydrate solution and sodium dodecyl sulfate (SDS) solution. These organo–inorgano complex montmorillonites were divided into three types (CM1, CM2 and CM3) depending on different intercalation processes. X-ray diffraction spectra, the Fourier transform infrared (FTIR) spectra were used to analyze the structure of the raw and modified montmorillonites. X-ray photoelectron spectra of the simples have been studied to determine spectral characteristics to allow the identification of Fe(III) hydroxide. The specific surface area of the host montmorillonite (M0) is 73.2 m²/g, while for the modified montmorillonites it is 114.0 m²/g, 117.2 m²/g, and 115.8 m²/g, respectively. The mesopore volumes of the montmorillonites decrease after modification. Ions of copper and cobalt were selected as adsorbates to evaluate the adsorption performance of each montmorillonite. The adsorption data was analyzed by both Freundlich and Langmuir isotherm models and the data was well fit by the Langmuir isotherm model. The adsorption was efficient and significantly influenced by metal speciation, metal concentration, contact time, and pH. Higher adsorption capacity of the modified montmorillonites were obtained at pH 5–6. The results of desorption indicated that the metal ions were covalently bound to the modified montmorillonites.     

环糊精基复合吸附剂的制备及对水中有机污染物去除的研究进展

目前水环境中有机物污染问题日趋严重,在诸多水处理技术中,吸附法具有成本低、效率高、简单易操作等优点,研发高效吸附剂是决定高效能吸附处理过程的关键因素。环糊精因其价格低廉、无毒、环境友好等优势在水污染处理领域具有广阔的应用前景。环糊精具有外部亲水、内部疏水的圆台状独特结构,利用内腔可与极性分子形成主-客体包含物,因此,被用于水溶液中有机污染物的去除,其外部结构中存在大量羟基,表现出良好的亲水性和优异的化学反应特性,能够实现对溶液中有机污染物的高效去除,通过多种化学修饰或各种材料的有效复合,达到环糊精基复合吸附剂的高效功能化拓展。本文总结了多种环糊精基复合材料的制备方法,重点综述其对水体中有机污染物高效吸附去除的应用研究,探讨环糊精基复合材料的研究趋势和研究热点,对其未来研究方向进行展望。     

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.     

Effect of the presence of excess ammonium ions on the clay surface on permeation properties of epoxy nanocomposites

Epoxy nanocomposites with commercially and self-modified montmorillonites of different cation exchange capacities carrying ammonium modifications of various chemical architectures were synthesized using solution casting approach. The commercially treated montmorillonites were observed to contain a large excess of unbound ammonium ions on the surface, which had a negative impact on the permeation properties of the composites owing to the suspected interactions of these unbound ammonium ions with the epoxy polymer. The permeation behavior was significantly improved when self-modified clays free of any excess ammonium modification were used. The microstructure development was unaffected by the physical state of the clay surface indicating that the potential changes in the polymer properties at the interface as well as interfacial interactions in the composites carrying the commercially modified clays may have led to increase in the free volume. Optimal preparation of the clay surface holds the key to achieve enhancement in the composite performance.     

Sulfobutylether-β-cyclodextrin/chitosan nanoparticles enhance the oral permeability and bioavailability of docetaxel

The aim of this research is to develop novel chitosan nanoparticles including cyclodextrins complexes for docetaxel (DTX), evaluate the performance of nanoparticles which could enhance the oral permeability and bioavailability of DTX in vitro and in vivo. DTX/sulfobutylether-β-cyclodextrin inclusion complexes were made and it was the main ingredient to prepare the DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles due to their promising physicochemical properties. DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles were prepared by the ionic gelation of chitosan with tripolyphosphate in the presence of cyclodextrins. Results indicated that DTX/sulfobutylether-β-cyclodextrin inclusion complexes and docetaxel/sulfobutylether-β-cyclodextrin/chitosan nanoparticles both had good performances in the studies of release and the rat small intestinal absorption in vitro. DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles showed preferable capability in improving the small intestinal absorption and inhibiting the efflux of DTX. In pharmacokinetics study, the DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles increased the AUC_0→t and decreased the clearance significantly, and the oral relative bioavailability of the DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles was as high as 1447.53% compared to the pure DTX formulation. The DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles prepared in this study have a good prospect for oral administration as an alternative of current DTX formulations.