Β-cyclodextrin Inclusion Complex Research Articles

One-pot method for the synthesis of β-cyclodextrin and covalent organic framework functionalized chiral stationary phase with mixed-mode retention mechanism

As a welcomed porous material, covalent organic frameworks (COFs) have many advantages and are widely used in various aspects. Particularly, COFs have aroused great attentions of scientists in chromatographic separation field due to their outstanding advantages, such as high stability, large specific surface area and multiple voids. However, endowing COFs with chirality to construct chiral stationary phase (CSP) function is still facing many challenges. Here, we firstly prepared a β-cyclodextrin (β-CD) and covalent organic framework functional silica CSP named as COF@CD@SiO2 by one-pot method to perform high performance liquid chromatography (HPLC) chiral separation. The morphology and structure of the synthesized stationary phase were investigated by a variety of characterization methods including Fourier transform infrared spectrometry (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), N2 adsorption experiment, powder X-ray diffraction (XRD) and elemental analysis (EA). The prepared stationary phase realized fast separation of six enantiomers in a short time. The separation mechanism was mainly ascribed to the inclusion complexation of β-cyclodextrin and the mutli-interaction sites from COFs material. In conclusion, the prepared chiral column can be used to achieve fast separation of enantiomers with good stability and reproducibility. These results can open new avenue for using chiral COFs in liquid chromatographic separation.

DEVELOPMENT AND CHARACTERIZATION OF TACROLIMUS TABLET FORMULATIONS FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism. Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics. Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87. Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism.

Formulation of ternary genistein β-cyclodextrin inclusion complex: In vitro characterization and cytotoxicity assessment using breast cancer cell line

Genistein (GT) is a poorly water-soluble flavonoid and reported for different biological activity. The present work was designed to prepare the inclusion complex using β-Cyclodextrins (β-CDs) as complexing agent and D -α-Tocopherol polyethylene glycol 1000 succinate (TPGS) as ternary substance to enhance the solubility and in vitro activity. The inclusion complex was prepared by solvent evaporation method and characterized for different physicochemical parameters. The selected GT ternary inclusion complex was further evaluated for in vitro antioxidant and cell viability study against breast cancer cell line. The phase solubility study result data revealed significantly marked enhancement in the solubility of GT. The complexation efficiency (CE) and stability constant (Ks) of GTBIC and GTTIC2 was found to 0.31% and 0.48% as well as 419.67 M-1 and 654.98 M-1, respectively. The saturation solubility results depicted a significant (p < 0.05) enhancement in the saturation solubility (2.61 and 5.27-fold) of GT. Genistein ternary inclusion complex (GTTIC2) prepared with TPGS (0.05%, w/w) showed the maximum release pattern 96.5 ± 3.98% in 90 min. The DSC and XRD spectra showed the transformation of crystalline GT into the amorphous state after complexation. The infrared (IR) and nuclear magnetic resonance (NMR) spectra confirms the formation of inclusion complex by showing changes in the characteristic peaks. GTTIC2 formulation exhibited significantly greater in-vitro antioxidant and cell viability activity against MCF7 cell than pure GT. The improved activity can be attributed to the enhanced solubility of Genistein by effective complexation in β-CDs and TPGS.

Silver Abietate and β-Cyclodextrin Inclusion Complex Doped Poly(vinyl alcohol) Nanowebs.

In this study, guesthost inclusion complexes of silver abietate with β-cyclodextrin were prepared by kneading and physical mixing techniques, and analyzed via fourier transformed infrared spectroscopy (FTIR) and thermogravimetric analyser (TGA). The 1:1 and 1:2 stoichiometry of the guesthost were prepared. Obtained FTIR and TGA results showed that formation of silver abietate:β-cyclodextrin (Ag-A:β-CD) inclusion complexes occurred at a mass ratio of both 1:1 and 1:2. Furthermore, prepared Ag-A:β-CD (1:2) inclusion complex was doped in Poly(vinyl alcohol) nanofibers during electrospinning process for obtaining nanowebs. The formation of nanowebs were investigated under scanning electron microscope (SEM), X-Ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR) and thermogravimetric analyser (TGA). The results confirmed Ag-A:β-CD inclusion complex containing Poly(vinyl alcohol) (PVA) nanoweb production.

Effect of hydrophilic polymer on solubility and taste masking of linezolid in multi-component cyclodextrin inclusion complex: Physicochemical characterization and molecular docking

The current work deals with the effect of hydrophilic polymer in a multi-component β-cyclodextrin (βCD) inclusion complex for enhancement of solubility and taste masking ability of linezolid (LZ). The phase solubility studies indicated the formation of 1:1 M stoichiometric ratio of LZ to βCD in all complexes in presence or absence of hydrophilic polymer (HPMC e5LV). The high stability constant (Ks; 1089 M−1, 1393 M−1), complexation efficiency (CE; 3.347, 3.761) and more negativity of Gibbs free energy (ΔG; −238.69, −1019.61) of ternary complexes in presence of 2.5% w/v and 5% w/v of HPMCe5LV was compared with binary system (Ks, 1024 M−1: CE, 2.571: ΔG, −59.91), which resulted in the improved complexation stability and solubilizing efficiencies. Solid inclusion complexes of LZ-βCD were prepared in 1:0.3 M ratio by kneading, co-evaporation, physical mixing and microwave irradiation methods with or without addition of HPMC e5LV. The drug content, solubility, dissolution and taste masking of LZ in ternary complexes were significantly higher (p < 0.05) than the binary complexes. The lowest MDT value (0.34 ± 0.007), highest value of DE (30mts) (28.9 ± 0.05) and R (15mts) (70.33 ± 0.57) were observed in case of solid inclusion complexes prepared by microwave irradiation method. The negative binding affinity found in molecular docking indicated the high stability of the ternary complex. No interaction was found in LZ, βCD and HPMC e5LV when analyzed by FTIR study. XRD and DSC results revealed that more amorphization of LZ in presence of βCD and HPMC e5LV. It infers that the multi-component system by microwave irradiation method can be a promising approach for increasing solubility with better palatability.

Eucalyptol/ β-cyclodextrin inclusion complex loaded gellan/PVA nanofibers as antifungal drug delivery system

Fungal infections pose a serious threat to humankind due to the toxicity of conventional antifungal therapy and continuous emerging incidence of multidrug resistance. Essential oils fascinated researchers because of their broad antimicrobial activity and minimal cytotoxicity. However, hydrophobic, volatile and low water solubility of essential oils hinder their applications in pharmaceutical industries. Therefore, in this study we have loaded eucalyptol/ β-cyclodextrin inclusion complex to gellan/polyvinyl alcohol nanofibers (EPNF) to eradicate Candida albicans and Candida glabrata biofilms. The electrospun nanofibers characterized by various physicochemical techniques and it was observed that EPNF possess highly hydrophilic surface property that facilitate rapid drug release. EPNF inhibited approximately 70% biofilm of C. albicans and C. glabrata. Time kill results depicted that eucalyptol (EPTL) encapsulation in the nanofibers prolonged its antifungal activity than the pure EPTL. Electron microscopy studies revealed that EPNF disrupted the cell surface of Candida. Collectively the current study suggested nanofiber encapsulation enhanced antibiofilm activity of eucalyptol and these nanoscale systems can serve as an alternative therapeutic strategy to treat fungal infections. Further, the developed nanofibrous materials can be applied as cost effective coating agent for biomedical implants.

Advancing insights on β-cyclodextrin inclusion complexes with SSRIs through lens of X-ray diffraction and DFT calculation

Depression—the global crisis hastened by the coronavirus outbreak, can be efficaciously treated by the selective serotonin reuptake inhibitors (SSRIs). Cyclodextrin (CD) inclusion complexation is a method of choice for reducing side effects and improving bioavailability of drugs. Here, we investigate in-depth the β-CD encapsulation of sertraline (STL) HCl (1) and fluoxetine (FXT) HCl (2) by single-crystal X-ray diffraction and DFT complete-geometry optimization, in comparison to the reported complex of paroxetine (PXT) base. X-ray analysis unveiled the 2:2 β-CD–STL/FXT complexes with two drug molecules inserting their halogen-containing aromatic ring in the β-CD dimeric cavity, which are stabilized by the interplay of intermolecular O2–H⋯N1–H⋯O3 H-bonds, C3/C5–H⋯π and halogen⋯halogen interactions. Similarly, the 1:1 β-CD–tricyclic-antidepressant (TCA) complexes have an exclusive inclusion mode of the aromatic ring, which is maintained by C3/C5–H⋯π interactions. By contrast, the 2:1 β-CD–PXT complex has a total inclusion that is stabilized by host–guest O6–H⋯N1–H⋯O5 H-bonds and C3–H⋯π interactions. The inherent stabilization energies of 1 and 2 evaluated using DFT calculation suggested that the improved thermodynamic stabilities via CD encapsulation facilitates the reduction of drug side effects. Moreover, the SSRI conformational flexibilities are thoroughly discussed for understanding of their pharmacoactivity.

Formation and stabilization mechanism of β-cyclodextrin inclusion complex with C10 aroma molecules

The formation and stabilization mechanisms of inclusion complexes (ICs) between β-cyclodextrin (β-CD) and five C10 aroma molecules were simultaneously investigated using experimental methods and molecular dynamics (MD) simulation. XRD, thermodynamic, FTIR and NMR analyses confirmed the formation of inclusion complexes, which had a new crystal structure and better thermal stability. MD simulation based on the molecular level including molecular structure (RMSD and Rg), solubility (RDF and SASA), interaction energy (Coul, vdW and H-bonds), and solvation and binding free energy, further clarified the properties of the inclusion complexes. The aroma molecules cause conformational changes in the inclusion complexes. The solubility of the inclusion complexes was lower than that of β-CD. The main driving force for the spontaneous entrance of aroma molecules into the cavity is van der Waals interactions. H-bonds are closely related to conformational changes, interactions and solubility.

Enantioseparation of phenethylamines by using high-performance liquid chromatography column permanently coated with methylated β-cyclodextrin.

Cyclodextrins and their derivatives have been used for chiral high-performance liquid chromatography selectors, while they are costly to use as mobile phase additives in high-performance liquid chromatography. Here, we report application of phenyl column coated permanently with methylated β-cyclodextrin for chiral high-performance liquid chromatography. A 0.1% (v/v) phosphoric acid solution containing 1M NaCl and 0.5% (w/v) methylated β-cyclodextrin was subjected to a phenyl column at a flow rate of 0.5mL/min at 30°C for 2 h. Using the precoating phenyl column, all the enantiomers of the four phenethylamines (norepinephrine, epinephrine, octopamine, and synephrine) were successfully separated simultaneously by high-performance liquid chromatography with a mobile phase without methylated β-cyclodextrin at a flow rate of 0.2mL/min at 30°C. The enantioseparation ability was retained for successive analyses during 1 week. It is suggested that inclusion complex of methylated β-cyclodextrin with a phenyl group on the surface of the stationary phase could be formed and that the inclusion complex could form the ternary complex with the injected analytes. The longer retention time of (S)-enantiomers of analytes than corresponding (R)-enantiomers for high-performance liquid chromatography could be explained from the higher stability of the methylated β-cyclodextrin complexes with (S)-enantiomers, which were confirmed by capillary electrophoresis and 1 H NMR spectroscopy experiments.

β-Cyclodextrin Inclusion Complexes with Catechol-Containing Antioxidants Protocatechuic Aldehyde and Protocatechuic Acid-An Atomistic Perspective on Structural and Thermodynamic Stabilities.

Protocatechuic aldehyde (PCAL) and protocatechuic acid (PCAC) are catechol derivatives and have broad therapeutic effects associated with their antiradical activity. Their pharmacological and physicochemical properties have been improved via the cyclodextrin (CD) encapsulation. Because the characteristics of β-CD inclusion complexes with PCAL (1) and PCAC (2) are still equivocal, we get to the bottom of the inclusion complexation by an integrated study of single-crystal X-ray diffraction and DFT full-geometry optimization. X-ray analysis unveiled that PCAL and PCAC are nearly totally shielded in the β-CD wall. Their aromatic rings are vertically aligned in the β-CD cavity such that the functional groups on the opposite side of the ring (3,4-di(OH) and 1-CHO/1-COOH groups) are placed nearby the O6–H and O2–H/O3–H rims, respectively. The preferred inclusion modes in 1 and 2 help to establish crystal contacts of OH⋅⋅⋅O H-bonds with the adjacent β-CD OH groups and water molecules. By contrast, the DFT-optimized structures of both complexes in the gas phase are thermodynamically stable via the four newly formed host–guest OH⋯O H-bonds. The intermolecular OH⋅⋅⋅O H-bonds between PCAL/PCAC 3,4-di(OH) and β-CD O6–H groups, and the shielding of OH groups in the β-CD wall help to stabilize these antioxidants in the β-CD cavity, as observed in our earlier studies. Moreover, PCAL and PCAC in distinct lattice environments are compared for insights into their structural flexibility.

Antioxidant activity of β-cyclodextrin inclusion complexes containing trans-cinnamaldehyde by DPPH, ABTS and FRAP.

This study was carried out to observed β-cyclodextrin (β-CD) inclusion complexes containing trans-cinnamaldehyde (CIN) by using DPPH, ABTS and FRAP assay. Antioxidative ability was compared between pure CIN and β-CD-CIN inclusion complexes and particle size, encapsulation efficiency, and temperature-dependent release of inclusion complexes were investigated. High concentration of β-CD (1.8%) as well as guest oil 1:3 molar ratio (β-CD:CIN) influenced on particle size bigger during self-assembly process. And particle sizes were increased as storage period. In the antioxidant capacity results, pure β-CD (1.8%) was antioxidative without CIN especially at FRAP assay. Antioxidant activity dramatically increased after 1:1 molar ratio (1.8% β-CD:CIN), especially at DPPH assay and ABTS•+ assay. In this study, β-CD complexation enhanced CIN solubility and affected increase the antioxidant activity of the CIN. Moreover, we need to consider that molar ratio of between β-CD concentration and CIN is effective manufacturing condition to improve antioxidant activity of β-CD-CIN inclusion complexes.

Ultrasonication-assisted host–guest inclusion complexes of β-cyclodextrins and 5-hydroxytryptophan: Enhancement of water solubility, thermal stability, and in vitro anticancer activity

The use of ultrasonic waves for the preparation of inclusion complexes in pharmaceutical industries has increased, owing to their versatility, promising nondestructive capability, and short reaction time. 5-Hydroxytryptophan (5-HTP), a precursor of serotonin, is used therapeutically, in the clinical setting, for psychiatric disorders such as anxiety and depression. In this study, 5-HTP is used as a guest molecule to prepare β-cyclodextrins (CDs; β-CD, HPβ-CD, and SBEβ-CD) inclusion complexes with the assistance of the ultrasonic method. The solubility of 5-HTP increases linearly as the concentration of CDs increased, confirming the 1:1 stoichiometry of the complex, obtained using UV–visible and fluorescence spectroscopy. The structural characteristics of the solid inclusion complexes are analyzed using various spectroscopic and microscopic techniques such as FTIR spectroscopy, PXRD, TGA, and FE-SEM. Molecular modeling elucidates the most stable inclusion model and phase solubility studies indicate that 5-HTP and SBEβ-CD form a 1:1 inclusion complex with an apparent stability constant of 1592.5 M−1. Furthermore, in vitro cytotoxicity studies show that the CDs:5-HTP complex has a better antitumor efficacy than pure 5-HTP. Thus, ultrasonication can be utilized as an advanced, time-saving, and cost-effective method for the generation of CDs:5-HTP inclusion complexes, resulting in the potential development of anticancer drugs.

Optimally controlled morphology and physico-mechanical properties of inclusion complex loaded electrospun polyvinyl alcohol based nanofibrous mats for therapeutic applications

Hydrophilic polyvinyl alcohol (PVA) based electrospun nanofibrous mats (ENMs) are recently being used for the designing and fabrication of active wound dressing materials. Thus, in this study an inclusion complex (IC) of curcumin (CUR) and β-cyclodextrin (β-CD) was optimally incorporated in electrospun PVA nanofibers, to obtain uniform bead-free nanofibers with minimum average diameter and variation using Taguchi’s design of experiments (DOE). The optimum level parameters were ascertained using Taguchi’s methodology, to obtain IC loaded PVA based bead-free ENMs, by varying IC (∼20, ∼40, and ∼60 wt.%) loading, applied voltage, solution concentration, and N, N-dimethylformamide (DMF) content in the electrospinning solution mixture. Validation experiments revealed a good agreement between the predicted and experimental values of fiber diameter, diameter-variation, and bead-numbers. Analysis of variance (ANOVA) showed a major influence of IC loading on the average fiber diameter and the number of bead defects, for IC-loaded PVA based ENMs. However, the DMF content of the solvent mixture significantly influenced the diameter variations of ENMs. The surface morphologies of ENMs were analyzed using Scanning Electron Microscopy (SEM) whereas the microstructural aspects were studied by Wide-Angle X-ray Diffraction (WAXD) and Fourier transform infrared (FT-IR) spectroscopy. The thermal properties were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) whereas the mechanical properties were measured by using uniaxial tensile testing and dynamic mechanical analysis (DMA). The variation in properties of IC loaded PVA based ENMs were correlated with neat PVA based ENMs fabricated using a similar set of optimized electrospinning process parameters. The study conceptually demonstrated the optimal designing of structurally-engineered hydrophilic IC loaded PVA based ENMs by using the Taguchi approach based on orthogonal DOE as potential drug release substrates.

Effect of the Croton rhamnifolioides Essential Oil and the Inclusion Complex (OEFC/β-CD) in Antinociceptive Animal Models

This study aims to evaluate the antinociceptive effect of the C. rhamnifolioides leaf essential oil (OEFC) and the β-cyclodextrin inclusion complex (COEFC) and investigate the pain signaling pathways involved in the antinociceptive response. The effects of the OEFC and COEFC on the central nervous system (CNS) were determined by open field and rota-rod assays, and the antinociceptive effect was evaluated via the acetic acid-induced abdominal contortions, formalin, and hot plate models. Swiss (Mus musculus) male mice (20–30 g) were used in both trials. The OEFC (200 mg/kg/v.o-orally) and COEFC (83.5 mg/kg/v.o.) did not present alterations in the CNS. The OEFC (25, 50, 100, and 200 mg/kg/vo.) and COEFC (8.35, 41.75, and 83.5 mg/kg/v.o.) demonstrated antinociceptive effects in the abdominal contortions, formalin, and hot plate tests. The OEFC (25 mg/kg/v.o.) and COEFC (8.35 mg/kg/v.o.) doses showed that the antinociceptive effect involves the activation of the opioid, cholinergic, and vanilloid systems, as well as the L-arginine/NO and α-2 adrenergic receptor pathways. The antinociceptive potential the OEFC and COEFC demonstrate possible alternatives for the therapy of pain. However, the COEFC presented more significant effects at lower doses than the isolated OEFC, where this action may be justified by the properties and advantages of the complexation.

Antinociceptive and anti-inflammatory effect of Lippia pedunculosa Hayek essential oil and its β-cyclodextrin inclusion complex

Lippia pedunculosa Hayek (EOLp) presents tripanocid and amebicid effects. However essential oil needs to be further studied in experimental models of analgesia and inflammation once the prevalence of pain in the population generates great suffering and disability and the drugs most often used have undesirable side effects. We also evaluated whether the inclusion complex formulation EOLp/β-cyclodextrin (β-CD) was able to improve the antinociceptive activity of the EOLp alone. Data were evaluated by analysis of variance (ANOVA), followed by Tukey’s test. Differences were considered significant if p&lt;0.05. EOLp presented better antinociceptive effect when compared to the EOLp/β-CD inclusion complex. Thus, cyclodextrins appear not to be efficient for essential oils with peroxide substances. However, in peritonitis, EOLp reduced total leucocyte migration and IL-1β levels in the peritoneal fluid, which confirmed its anti-inflammatory effect. The observed effects suggest that EOLp is the best promising option for the treatment of inflammation and pain-related disorders.

Enhancing stability and antioxidant efficacy of fisetin by encapsulating as β-cyclodextrin inclusion complex with porous polylactic acid film from breath figure

This research aims to investigate the scope of fisetin (FIT)/β-cyclodextrin (β-CD) inclusion complexes with the ratios of 1:2 and 2:1 mole by means of freeze-drying, kneading and physical mixing methods (controlled process). Moreover, the complex compounds are analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The results show that the most suitable preparation method of fisetin (FIT)/β-CD complex is the freeze-drying method with the fisetin (FIT) to β-CD ratio at 1:2. The emission of FIT/β-CD was investigated and it is found that the emission rate of freeze-dried FIT/β-CD in 1:2 ratio by freeze-drying method is lower than that by kneading and physical mixing methods. These results lead to an initiation of the innovative active packaging materials with synthetic polylactic acid (PLA) porous film by breath figure (BF) method in order to entrap FIT/β-CD inclusion complex. The honeycomb structure with and without the FIT/β-CD complex were analyzed by Scanning Electron Microscopy (SEM). Thereafter, the effectiveness of Antioxidant Activities (%AA) of the porous PLA films is measured by the anti-oxidation caused by 2,2-diphenyl-1-picrylhydrazyl (DPPH method). The result shows that PLA entrapping complex fisetin is more effective than PLA entrapping pure fisetin, by result of 53.0% and 48.6%, respectively.

Evaluation of Enhanced UV Protection Property of Dyed Cotton Fabrics Based on Inclusion Complex of β-cyclodextrin with Natural Coumarin Extracted from Cortex fraxini

Inclusion complex formed between β-cyclodextrin (β-CD) and natural coumarins extracted from Cortex fraxini were utilized to dye and enhancing the UV protection properties of cotton fabric. Natural coumarins were extracted from Cortex fraxini and the total amount of natural coumarins was evaluated. The inclusion complex of natural coumarins with β-CD were formed and analyzed by ultraviolet-visible spectrum, fluorescence spectroscopy, FTIR and TGA. The obtained results showed that a stoichiometry of 1:1 inclusion complex was formed and the fluorescence intensities and ultraviolet absorption of the natural coumarins were both enhanced by incorporating into β-CD. β-CD was grafted onto cotton fabric based on esterification of citric acid with cellulose and cyclodextrin in the presence of sodium hypophosphite. The grafted cotton fabric was then dyed with natural coumarins extraction of Cortex fraxini as natural ultraviolet absorbent to form stable inclusion complex. UV protection factor (UPF), UVA transmittance (TUVA) and UVB transmittance (TUVB), wrinkle recovery and tensile strength of dyed fabrics were evaluated and demonstrated that graft modification of fabrics with β-CD resulted enhancement in UV protection property and durability accompanied with increasing in wrinkle recovery properties and decreasing in tensile strength. Furthermore, apparent morphology, FTIR and TGA analysis of inclusion complexes loaded cotton fabrics and the relationship between structure and properties were investigated.

Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex-Compatibility Study with Pharmaceutical Excipients.

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.

Complexation of an Azo Dye by Cyclodextrins: A Potential Strategy for Water Purification.

The chemistry of the host–guest complex formation has received much attention as a highly efficient approach for use to develop economical adsorbents for water purification. In the present study, the synthesis of three β-cyclodextrin (β-CD) inclusion complexes with the oil orange SS (OOSS) azo dye as a guest molecule and their potential applications in water purification are described. The complexes were synthesized by the coprecipitation method and characterized by Fourier transform infrared (FTIR) spectroscopy, UV–vis spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). FTIR and thermal analyses confirmed the encapsulation of OOSS dye within the hydrophobic cavity of β-CD. The encapsulation of hydrophobic dye inside the β-CD cavity was mainly due to the hydrophobic–hydrophobic interaction. The results showed that the stability of the OOSS dye had been improved after the complexation. The effect of three different compositions of the host–guest complexes was analyzed. The present study demonstrated that the hydrophobic dye could be removed from aqueous solution via inclusion complex formation. Thus, it can play a significant role in removing the highly toxic OOSS dye from the industrial effluent.

Formation of Rutin-β-Cyclodextrin Inclusion Complexes by Supercritical Antisolvent Precipitation.

In this work, rutin (RUT)–β-cyclodextrin (β-CD) inclusion complexes are prepared by Supercritical AntiSolvent (SAS) precipitation. Well-defined composite microparticles are obtained at guest:host ratios equal to 1:2 and 1:1 mol:mol. The dimensions of composite particles range between 1.45 ± 0.88 µm and 7.94 ± 2.12 µm. The formation of RUT–β-CD inclusion complexes has been proved by different analyses, including Fourier transform infrared spectroscopy, Differential Scanning Calorimetry, X-ray diffraction, and UV-vis spectroscopy. The dissolution tests reveal a significant improvement in the release rate of RUT from inclusion complexes. Indeed, compared to the unprocessed RUT, the dissolution rate is about 3.9 and 2.4 times faster in the case of the complexes RUT–β-CD 1:2 and 1:1 mol:mol, respectively. From a pharmaceutical/nutraceutical point of view, CD-based inclusion complexes allow the reduction of the polymer amount in the SAS composite formulations.