Stoichiometric Inclusion Complex Research Articles

Formulation of Ensulizole with Beta-Cyclodextrins for Improved Sunscreen Activity and Biocompatibility

In today's context, prolonged exposure to sunlight is widely recognized as a threat to human health, leading to a range of adverse consequences, including skin cancers, premature skin aging, and erythema. To mitigate these risks, preventive actions mainly focus on advocating the application of sunscreen lotions and minimizing direct exposure to sunlight. This research study specifically centered on ensulizole (ENS), a prominent ingredient in sunscreens. The objective was to create inclusion complexes (ICs) with Beta-cyclodextrin (B–CD) and its hydroxypropyl derivatives (H–CD). Using phase solubility measurements, we determined that both B–CD and H–CD form 1:1 stoichiometric ICs with ENS. Proton nuclear magnetic resonance spectral (1H NMR) analysis confirmed that the phenyl portion of ENS is encapsulated within the B–CD cavity. Significant changes in surface morphology were observed during the formation of these ICs compared to ENS and CDs alone. Quantum mechanical calculations were employed to further support the formation of ICs by providing energy data. Particularly, the photostability of the ENS:B–CD ICs remained intact for up to four hours of UV exposure, with no significant alterations in the structure of ENS. Furthermore, comprehensive biocompatibility assessments yielded encouraging results, suggesting the potential application of these inclusion complexes in cosmetics as a UVB sunscreen. In summary, our research underscores the successful creation of inclusion complexes characterized by enhanced photostability and safe biocompatibility.

Preparation, Characterization and Molecular Dynamics Simulation of Rutin-Cyclodextrin Inclusion Complexes.

Rutin is a natural flavonoid that carries out a variety of biological activities, but its application in medicine and food is limited by its water solubility. One of the classical methods used to enhance drug solubility is encapsulation with cyclodextrins. In this paper, the encapsulation of different cyclodextrins with rutin was investigated using a combination of experimental and simulation methods. Three inclusions of rutin/beta-cyclodextrin (β-CD), rutin/2-hydroxypropyl beta-cyclodextrin (HP-β-CD) and rutin/2,6-dimethyl beta-cyclodextrin (DM-β-CD) were prepared by the freeze-drying method, and the inclusions were analyzed using Fourier infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and ultraviolet-visible spectroscopy (UV) to characterize and demonstrate the formation of the inclusion complexes. Phase solubility studies showed that rutin formed a 1:1 stoichiometric inclusion complex and significantly increased its solubility. β-CD, HP-β-CD, DM-β-CD, rutin and the three inclusion complexes were modeled by using MS2018 and AutoDock 4.0, and molecular dynamics simulations were performed to calculate the solubility parameters, binding energies, mean square displacement (MSD), hydrogen bonding and radial distribution functions (RDF) after the equilibration of the systems. The results of simulation and experiment showed that rutin/DM-β-CD had the best encapsulation effect among the three cyclodextrin inclusion complexes.

Recognition of d-Glucose in Water with Excellent Sensitivity, Selectivity, and Chiral Selectivity Using γ-Cyclodextrin and Fluorescent Boronic Acid Inclusion Complexes Having a Pseudo-diboronic Acid Moiety.

Fluorescence recognition of d-glucose in water with excellent sensitivity, selectivity, and chiral selectivity is desired because d-glucose is an essential component in biological and pathological processes. We report an innovative approach that exploits the 1:2 stoichiometric inclusion complexes of γ-cyclodextrin (γ-CyD) with two molecules of fluorescent monoboronic acid-based receptors, which form a pseudo-diboronic acid moiety as the recognition site for d-glucose in water. Two monoboronic acids (1F and 2N) were easily synthesized without heating or column purification. The 1:2 stoichiometric inclusion complexes (1F/γ-CyD and 2N/γ-CyD) were prepared in a mixture of dimethyl sulfoxide/water (2/98 in v/v) by mixing γ-CyD and the corresponding monoboronic acids. Both 1F/γ-CyD and 2N/γ-CyD exhibited strong turn-on response to d-glucose with excellent selectivity over nine other saccharides in the water-rich solvent at pH 7.4 owing to the ditopic recognition of d-glucose by the pseudo-diboronic acid moieties. The limits of detection of 1F/γ-CyD and 2N/γ-CyD for d-glucose were 1.1 and 1.8 μM, respectively, indicating the remarkable sensitivity for the detection of d-glucose at μM levels. 1F/γ-CyD and 2N/γ-CyD also demonstrated chiral-selective recognition of d-glucose, which is apparent from the 2.0- and 6.3-fold enhancement of fluorescence by the addition of d-glucose relative to l-glucose addition, owing to the chiral pseudo-diboronic acid moieties produced by the chiral γ-CyD cavity. To the best of our knowledge, 2N/γ-CyD has the highest d/l selectivity among hitherto reported fluorescent diboronic acid-based receptors.

Interaction mechanism of cholesterol/β-cyclodextrin complexation by combined experimental and computational approaches

It is crucial to accurately describe non-covalent weak interactions between the components of cholesterol/β-cyclodextrin inclusion complex in the modulation of its stability. Experimental and theoretical infrared spectra confirmed that the inclusion complex was successfully prepared. Phase solubility studies suggested the formation of 1:1 stoichiometric inclusion complex of cholesterol with β-CD. The inclusion complex showed higher decomposed temperature (327.3 °C) than physical mixture (321.6 °C), indicating improved thermal stability of inclusion complex. Conformational search and density functional theory calculations were performed to find the most stable conformation with the lowest complexation energy (−129.66 kJ/mol). Dispersion energy from van der Waals (−283.31 kJ/mol) contributed greatly on total bonding energy (−204.72 kJ/mol). The bond lengths of hydrogen bonds (O127⋅⋅⋅H221 and O220⋅⋅⋅H107) were 1.77 and 1.62 Å, respectively. Van der Waals and hydrogen bonds were necessary to drive spontaneous formation and maintain the stability of inclusion complex. This study revealed a deep insight into the formation mechanism of cholesterol/β-CD inclusion complex using computational and experimental approaches, providing theoretical basis for the removal of cholesterol from hydrocolloid-containing systems. • Mechanism of β-CD complexation with cholesterol was illustrated through experimental and computational methods. • The thermal stability of cholesterol/β-CD inclusion complex was significantly improved. • Weak interactions of the complex were shown by means of images and data. • The inclusion complex was mainly stabilized by hydrogen bonds and van der Waals forces.

Prebiotic-like cyclodextrin assisted silybin on NAFLD through restoring liver and gut homeostasis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no currently approved treatment. The natural compound silybin (SLN) has versatile hepatoprotective efficacy with negligible adverse effects; however, poor absorption limits its clinical applications. Gut microbiota has been proposed to play a crucial role in the pathophysiology of NAFLD and targeted for disease control. Cyclodextrins, the cyclic oligosaccharides, were documented to have various health benefits with potential prebiotic properties. This study aimed to develop a silybin-2-hydroxypropyl-β-cyclodextrin inclusion (SHβCD) to improve the therapeutic efficacy of SLN and elucidate the mechanisms of improvement. The results showed that SLN formed a 1:1 stoichiometric inclusion complex with HP-β-CD. The solubility of SLN was increased by generating SHβCD, resulting in improved drug permeability and bioavailability. In high-fat diet (HFD)-fed hamsters, SHβCD modulated gut health by restoring the gut microbiota and intestinal integrity. SHβCD showed superior anti-lipid accumulation, antioxidant, and anti-inflammatory effects compared with SLN alone. Transcriptome analysis in the liver tissue implied that the improved inflammation and/or energy homeostasis was the potential mechanism. Therefore, SHβCD may be a promising alternative for the treatment of NAFLD, attributing to the dual functions of HβCD on drug absorption and gut microbial homeostasis.

Host-guest inclusion complexes of sulfabenzamide with β- and methyl-β-cyclodextrins: Characterization, antioxidant activity and DFT calculation

The inclusion complexation behavior, characterization and binding ability of sulfabenzamide (SBZ) with β-cyclodextrin (β-CD) and methyl-β-cyclodextrin (Mβ-CD) have been investigated both in solution and solid state by different experimental techniques. Sulfabenzamide drug having poor water solubility and slow dissolution. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The spectral shifts revealed that part of aniline ring of SBZ is entrapped in the CD cavity. The association constants were determined by Benesi-Hildebrand plots and spectroscopic studies. The phase solubility studies were carried using two different types of cyclodextrins viz., β, methyl-β cyclodextrins. The phase solubility profiles with all the two cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, FTIR, 1HNMR, XRD and SEM studies. We investigated the interaction of the host–guest Mβ-CD/SBZ complex by means of molecular dynamics simulation using a density functional based tight-binding code (DFT).

Molecular simulation and experimental study on the inclusion of rutin with β-cyclodextrin and its derivative

Rutin is a natural flavonoid compound with various biological activities, but its low water solubility limits its applications in the food and pharmaceutical fields. Complexation with cyclodextrins (CDs) is a powerful method to improve the poorly solubility of rutin, whereas the mechanism for the inclusion still needs to be explored. This study investigated the characteristic and mechanism for inclusion of rutin with β-cyclodextrin (β-CD) and 2,6 dimethyl-β-cyclodextrin (DM-β-CD). The molecular simulation provided the possible inclusion structure and revealed that the combination of rutin and CDs is a thermodynamically good process. It also indicated that the complex formed with DM-β-CD had better stability and water solubility compared with β-CD. Then the complexes of rutin with β-CD and DM-β-CD were prepared and characterized by FT-IR, XRD, and DSC analysis. Phase solubility studies demonstrated that the solubility of rutin was significantly enhanced by forming 1:1 stoichiometric inclusion complexes. The effect of DM-β-CD in improving the water solubility of rutin is 146% higher than that of β-CD, which was in accordance with the simulation predictions.

Photostability of the inclusion complex of isoamyl4-(Dimethylamino)benzoate with sulfobutylether-β-cyclodextrin

The inclusion complex of isoamyl 4-(Dimethylamino)benzoate (IDB) with sulfobutylether-β-cyclodextrin (SBE-β-CD) was prepared by freeze-drying method. The Benesi-Hildebrand method and Job’s plot showed that the IDB formed 1:2 stoichiometric inclusion complex with SBE-β-CD. The inclusion complex of SBE-β-CD with IDB was characterized by X-ray powder diffractometry (XRD), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), scanning electron microscopy (SEM), nuclear magnetic resonance (1H NMR) and two-dimensional rotational frame Overhauser effect spectroscopy (2D ROESY). The results of 1H NMR and 2D ROESY spectra showed that the hydrophobic group of IDB associated with SBE-β-CD from the wide and narrow side. The solubility and thermal stability of IDB were both improved after formed the inclusion complex. The photodegradation experiment showed that the photolysis ratio of IDB decreased from 9.16% to 2.25% due to the complexation of SBE-β-CD. It could be the potential way to promote its cosmetic application in UVB sunscreen.

Enhanced production of 2-phenylethanol by salicylic acid and cyclodextrins in cell suspension cultures of the unexplored filamentous fungus Monochaetinula geoffroeana.

2-Phenylethanol (PEA) is a higher aromatic alcohol with a rose-like odor, which is used in several industries. Although PEA can be synthesized, consumers are increasingly concerned about the toxicity of chemically synthesized products, and prefer natural aroma compound. PEA occurs naturally in the environment but concentrations are too low to justify extraction. The present study offers a novel biological source of PEA: the filamentous fungi Monochaetinula geoffroeana. We report the highest recorded yield of PEA of fungal origin to date: 6.52 g L-1 . The volatility and low water solubility of PEA can affect its use in many industries, for which reason complexation studies of PEA and cyclodextrins were carried out using the phase solubility technique. PEA formed 1:1 stoichiometric inclusion complexes with natural and modified CDs, the highest encapsulation constant being obtained with MβCD (K1:1 =299.88 L mol-1 ). The complexation process significantly increased the water solubility of PEA. A computational study showed a high degree of correlation between computed scores and experimental values. Furthermore, this study reports the role of salicylic acid as an effective elicitor for improved PEA production by the studied fungi. Supplementation with 10 μmol L-1 salicylic acid increased PEA production from 6.52 to 10.54 g L-1 . The best treatment to enhance PEA production by M. geoffroeana under laboratory conditions was to use salicylic acid 10 μmol L-1 . Due to the commercial importance of PEA, further investigation is needed to improve PEA production by M. geoffroeana and to optimize culture conditions in order to standardize yields. © 2021 Society of Chemical Industry.

Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance.

The interaction between meloxicam and sulfonatocalix[4]naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix[4]naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix[4]naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4–65.28 folds and 7.3–90.7, respectively. In conclusion, sulfonatocalix[4]naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.

Inclusion Complex of Gedunin-2-Hydroxypropyl-Β-Cyclodextrin Prepared by Kneading and Freeze-Drying Methods: Synthesis and Structural Characterization

Abstract The potential application of gedunin, a pharmacologically active limonoid, is limited in medicine because it has poor aqueous solubility. This study was aimed at preparation and characterization of an inclusion complex of gedunin and 2-hydroxypropyl-β-cyclodextrin (HBD) to increase the solubility in aqueous solvents and thus enhance the possibility of pharmaceutical formulation and oral administration of gedunin. Inclusion complex of gedunin isolated from Entandrophragma angolense heartwood with 2-hydroxypropyl-β-cyclodextrin (HBD) was prepared using freeze-drying and kneading methods. The gedunin-2-hydroxypropyl-β-cyclodextrin complex (GCD) was characterized using elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (1H-NMR) and X-ray diffraction analysis (XRD). Elemental analysis indicated that gedunin and HBD formed 1:1 stoichiometric inclusion complex. Results of FT-IR indicated that gedunin was stabilized in HBD cavity by intra-molecular hydrogen bonds and van der Waals forces. 1H-NMR revealed that the entire gedunin molecule was not trapped into the core of the HBD. Nevertheless, the fraction trapped may be sufficient to enhance the apparent solubility of gedunin. XRD results showed the formation of new solid crystalline phase. The results obtained by different characterization techniques clearly indicated that both kneading and freeze-drying methods led to inclusion complex formation which may enhance oral administration of gedunin.

Structural elucidation of novel isoquercitrin-γ-cyclodextrin (IQC-γCD) molecular inclusion complexes of potential health benefits

Isoquercitrin has a higher bioavailability than quercetin and has various pharmacological effects. In the present study, we aim to elucidate the structure of the novel isoquercitrin-γ-cyclodextrin (IQC-γCD) inclusion complex derived through controlled enzymatic hydrolysis of rutin into isoquercitrin in-situ included in γ-cyclodextrin. Several vibrational, electronic and analytical spectral measurement techniques (FTIR, 1H-NMR, 13C-NMR, UV-Vis, DSC, PXRD, Raman spectroscopy, and SEM) were employed. The detailed structural comparison of the IQC-γCD inclusion complex with isolated isoquercitrin revealed the shielding of isoquercitrin –OH groups inside the γ-CD cavity, and thus, confirmed the successful formation of the inclusion complex that exhibit distinct spectroscopic features from both guest and host molecules. The phase-solubility studies showed that isoquercitrin formed a 1:1 stoichiometric inclusion complex with γ-CD. The aqueous solubility of isoquercitrin was significantly enhanced by complexation with γ-CD complex possibly due to increased isoquercitrin dissolution rate compared to the isolated isoquercitrin. The IQC-γCD inclusion could have enhanced pharmacokinetics that will be useful for future applications in functional foods and health benefits.

Exploring the effect of OSA-esterified waxy corn starch on naringin solubility and the interactions in their self-assembled aggregates

Octenyl succinic anhydride esterified waxy corn starches (OSAS) with five different molecular weights (MWs) were prepared by enzymatic hydrolysis and their effects on naringin solubility were studied. The MW of OSAS was found to significantly influence the amount of naringin embedded in the complex formed by self-aggregation. OSAS with medium MW (M−OSAS) formed complex with the highest naringin entrapment. This system showed an AL type water phase solubility curve (indicating a 1:1 stoichiometric inclusion complex) and an increase of 848.83 folds in naringin solubility. Further investigation on the interactions between M−OSAS and naringin using FTIR, XRD, DSC and NMR confirmed the encapsulation of naringin into the inner cavity of M−OSAS. TEM and particle size analysis indicated the complex was spherical in shape, having a mean particle size of 257.07 nm and size distribution of 10–1000 nm. This study has provided a basis for solubility enhancement of citrus flavonoids using OSAS.

Cyclodextrin Complexation for Enhanced Stability and Non-invasive Pulmonary Delivery of Resveratrol-Applications in Non-small Cell Lung Cancer Treatment.

Pulmonary drug delivery is a noninvasive therapeutic approach that offers many advantages including localized drug delivery and higher patient compliance. As with all formulations, the low aqueous solubility of a drug often poses a challenge in the formulation development. Thus, strategies such as cyclodextrin (CD) complexation have been utilized to overcome this challenge. Resveratrol (RES), a natural stilbene, has shown abundant anti-cancer properties. Due to many drawbacks of conventional chemotherapeutics, RES has been proposed as an emerging alternative with promising pharmacological effects. However, RES has limited therapeutic applications due to low water solubility, chemical stability, and bioavailability. This study was aimed at developing an inhalable therapy that would increase the aqueous solubility and stability of RES by complexation with sulfobutylether-β-cyclodextrin (SBECD). Phase solubility profiles indicated an optimal stoichiometric inclusion complex at 1:1 (SBECD:RES) ratio for formulation considerations. Physiochemical characterizations were performed to analyze CD-RES. Stability studies at pH7.4 and in plasma indicated significant improvement in RES stability after complexation, with a much longer half-life. The mass median aerodynamic diameter (MMAD) of CD-RES was 2.6 ± 0.7μm and fine particle fraction (FPF) of 83.4 ± 3.0% are suitable for pulmonary delivery and efficient deposition. Lung cancer was selected as the respiratory model disease, owing to its high relevance as the major cause of cancer deaths worldwide. Cell viability studies in 5 non-small-cell-lung-cancer (NSCLC) cell lines suggest CD-RES retained significant cytotoxic potential of RES. Taken together, CD-RES proves to be a promising inhalation treatment for NSCLC.

A deep insight into mechanism for inclusion of 2R,3R-dihydromyricetin with cyclodextrins and the effect of complexation on antioxidant and lipid-lowering activities

2R,3R-Dihydromyricetin (DMY) is a natural flavonoid that has versatile biological activities. However, due to its poor water solubility and low chemical stability, its applications in food and pharmaceutical fields remain limited. Inclusion of DMY with cyclodextrins (CDs) has been shown to improve the solubility and stability of DMY, whereas the mechanism for the inclusion has not been elucidated. This study investigated the characteristic and mechanism for inclusion of DMY with CDs, and evaluated the effects of complexation on antioxidant and lipid-lowering activities of DMY. Phase solubility studies revealed that the solubility of DMY was significantly improved in the presence of natural (α-, β-, γ-) CDs and their derivatives, namely hydroxypropyl-β-cyclodextrin (HP-β-CD) and (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), by forming 1:1 stoichiometric inclusion complexes. Particularly, the complexes of DMY with HP-β-CD and DM-β-CD were prepared and characterized by FT-IR, PXRD, DSC, SEM and NMR analysis. Furthermore, the possible inclusion configuration was verified by molecular docking, which indicated that B-ring of DMY was fully embedded in the cavity of CDs while C-ring and A-ring were partly included, through non-covalent interaction such as hydrogen bonding. The results also showed that inclusion of DMY with HP-β-CD or DM-β-CD enhanced the radical scavenging capacity of DMY and maintained its lipid-lowering effect in hyperlipidemia zebrafish model.

Inclusion complexation of novel synthesis amino acid based ionic liquids with β-cyclodextrin

Inclusion complex formation between amino acid based ionic liquids (AAILs) i.e., 1-(2-(octylamino)-2-oxoethyl)pyridin-1-ium bromide and 4-((hydroxyimino)methyl)-1-(2-(octylamino)-2-oxoethyl)pyridin-1-ium bromide into β-cyclodextrin have been investigated in solution. The inclusion complexes (ICs) of AAILs with β-CD were synthesized through the co-precipitation method. The solid IC formation is characterized by numerous analytical techniques, primarily by UV–vis spectroscopy and secondary by major techniques i.e., FT-IR and 1H NMR. The binding constant and 1:1 stoichiometric of ICs nature of the complex between AAILs and β-CD in solution were determined by Job's plot method using UV–vis spectroscopy. As results suggest, the binding constants of ICs are higher for OAOEPB-β-CD as compared to HIMOAOEPB-β-CD. The different thermodynamic parameters such as change in standard Gibbs free energy (ΔG0), standard enthalpy changes (ΔH0) and standard entropy change (ΔS0) have been estimated with the help of van't Hoff equation. Noteworthy changes of IR stretching frequency also support the IC formation. 1H NMR results suggest that the tail part of AAILs is more suitably included inside the hydrophobic cavity of β-CD and it shows 1:1 stoichiometric ICs formation.

Physicochemical properties of catechin/β-cyclodextrin inclusion complex obtained via co-precipitation

ABSTRACTInclusion complex of catechin (CAT) with β-cyclodextrin (β-CD) was prepared using co-precipitation method to enhance antioxidant stability of CAT and the physicochemical properties of the inclusion complex were studied. The CAT/β-CD inclusion complex was analyzed through phase solubility study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Phase solubility study indicated that CAT and β-CD formed 1:1 stoichiometric inclusion complex. Results of FT-IR indicated that CAT was stabilized in β-CD cavity by intra-molecular hydrogen bonds. Results of DSC and SEM proved that CAT/β-CD inclusion complex formed. XRD results showed that the formation of new solid crystalline phases in the CAT/β-CD inclusion complex. CAT was effectively protected through encapsulation into β-CD and the antioxidant stability of CAT was improved after encapsulation. In addition, the release behavior of CAT from the inclusion complex increased with increasing of the temperature.

Designing a Formulation of the Nootropic Drug Aniracetam Using 2-Hydroxypropyl-β-Cyclodextrin Suitable for Parenteral Administration.

The nootropic drug aniracetam is greatly limited in its application by low aqueous solubility and a poor oral bioavailability. The primary aim of this study was to design a parenteral formulation of aniracetam that can be administered intravenously. Complexation of aniracetam with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated as a strategy to enhance solubility. A phase solubility analysis was performed to quantify the extent of improvement. An 819% increase in the solubility of aniracetam was obtained, reaching 36.44 mg/mL. This marked increase enables aniracetam to exist in an aqueous solvent at levels sufficient for parenteral dosing. A stability test was then devised using a design of experiment approach. The aniracetam-HP-β-CD formulation was subjected to different relative humidity and temperature and cyclodextrin concentrations over a 12-week period. Key changes in FTIR vibrational frequencies suggest the benzene moiety of aniracetam was introduced into the hydrophobic cavity of HP-β-CD. These results are highly supportive of the formation of a predictable 1:1 molar stoichiometric inclusion complex, explaining the improvement seen in physiochemical properties of aniracetam following formulation with HP-β-CD. This novel formulation of aniracetam suitable for parenteral administration will have utility in future studies to further elucidate the pharmacokinetics of this drug.

Studies on the preparation and photostability of avobenzone and (2-hydroxy)propyl-β-cyclodextrin inclusion complex

The inclusion complex of avobenzone and (2-hydroxy)propyl-β-cyclodextrin (2-HP-β-CD) was prepared successfully. The effects of the inclusion behavior of avobenzone with 2-HP-β-CD were investigated in both solution and the solid state with the following methods: UV–vis spectrophotometry (UV–vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), proton nuclear magnetic resonance (1H-NMR) and two-dimensional rotational frame nuclear overhauser effect spectroscopy (2D ROESY). The photostability of avobenzone and its inclusion complex were both investigated by UV–vis spectrophotometry. The Benesi-Hildebrand’s method showed that avobenzone formed 1:2 stoichiometric inclusion complex with 2-HP-β-CD. The solubility, thermal stability and the photostability of avobenzone were all improved after encapsulating by the 2-HP-β-CD. Therefore, it can be a potentially promising way to promote its cosmetic preparations in UVA sunscreen.

Physicochemical characterization and in vitro dissolution performance of ibuprofen-Captisol® (sulfobutylether sodium salt of β-CD) inclusion complexes

The aim of the present research work was to explore the impact of ibuprofen-captisol® (sulfobutylether sodium salt of β-CD) inclusion complexes on in vitro dissolution performance. Phase solubility studies of ibuprofen using the carrier captisol® had generated AL-type profiles which indicated the formation of 1:1 stoichiometric inclusion complexes. The study revealed that more stable complexes of ibuprofen-captisol® were formed in double distilled water compared to phosphate buffer (pH7.2) as more fraction of the drug is in un-ionized form. Ibuprofen-captisol® complexes were prepared by (i) kneading and (ii) freeze-drying technique with the various drug-carrier ratio (1:1, 1:3 and 1:5w/w). Complex formation was explained on the basis of physical mixtures (PMs) of identical compositions. Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Scanning electron microscope (SEM) and Molecular docking studies were carried out to establish the inclusion complexation. Molecular docking confirmed the possibility of forming a complex between drug and polymer, and it was evident from the energy-minimized structure of the drug-polymer complex. Minimization of energy suggested the formation of a stable drug-polymer complex with binding energy of (−) 3.6kcalmol−1. The negative docking energy of the complex formation justifies the reason of its solubility enhancement. The complexes prepared by freeze-drying technique were found to be superior in the enhancement of in vitro dissolution rate of ibuprofen when compared to that of complexes prepared by kneading technique.