The development of an innovative method to improve the dissolution performance of rivaroxaban.

Recent advancements in the formulation of solid dosage forms involving active ingredient-cyclodextrin complexes have garnered considerable attention in pharmaceutical research. While previous studies predominantly focused on incorporating these complexes into solid states, issues regarding incomplete inclusion prompted the exploration of novel methods. In this study, we aimed to develop an innovative approach to integrate liquid-state drug-cyclodextrin inclusion complexes into solid dosage forms. Our investigation centered on rivaroxaban, a hydrophobic compound practically insoluble in water, included in hydroxypropyl-ß-cyclodextrin at a 1:1 M ratio, and maintained in a liquid state. To enhance viscosity, hydroxypropyl-cellulose (2 % w/w) was introduced, and the resulting dispersion was sprayed onto the surface of cellulose pellets (CELLETS®780) using a Caleva Mini Coater. The process parameters were meticulously controlled, with atomization air pressure set at 1.1 atm and a fluidizing airflow maintained at 35-45 m3/h. Characterization of the coated cellets, alongside raw materials, was conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. Physicochemical evaluations affirmed the successful incorporation of rivaroxaban into hydroxypropyl-ß-cyclodextrin, with the final cellets demonstrating excellent flowability, compressibility, and adequate hardness. Quantitative analysis via the HPLC-DAD method confirmed a drug loading of 10 mg rivaroxaban/750 mg coated cellets. In vitro dissolution studies were performed in two distinct media: 0.022 M sodium acetate buffer pH 4.5 with 0.2 % sodium dodecyl sulfate (mirroring compendial conditions for 10 mg rivaroxaban tablets), and 0.05 M phosphate buffer pH 6.8 without surfactants, compared to reference capsules and conventional tablet formulations. The experimental capsules exhibited similar release profiles to the commercial product, Xarelto® 10 mg, with enhanced dissolution rates observed within the initial 10 min. This research presents a significant advancement in the development of solid dosage forms incorporating liquid-state drug-cyclodextrin inclusion complexes, offering a promising avenue for improving drug delivery and bioavailability.

Cyclodextrins as a Strategy for Enhancing Solubility of Therapeutic Agents for Neglected Tropical Diseases: A Systematic Review.

BACKGROUND: Neglected Tropical Diseases (NTD) are chronic infectious conditions that primarily affect marginalized populations. The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases. This is exacerbated by the pharmaceutical industry's lack of interest in funding the development of new therapeutic alternatives. In addition, a considerable number of drugs used in NTD therapy have low aqueous solubility. To address this issue, solubility enhancement strategies, such as the use of inclusion complexes with cyclodextrins (CD) can be employed. OBJECTIVE: Therefore, this systematic review aims to present the application of CD in complexing with drugs and chemotherapeutic compounds used in the therapy of some of the most prevalent NTD worldwide and how these complexes can enhance the treatment of these diseases. METHODS: Two bibliographic databases, Science Direct and PubMed, were used to conduct the search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines. RESULTS: From a total of 978 articles, 23 were selected after applying the exclusion criteria. All the studies selected were consistent with the use of CD as a strategy to increase the solubility of therapeutic agents used in NTD. CONCLUSION: The results indicate that CD can enhance the solubility of chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTD). This review presents data that clearly highlights the potential use of CD in the development of new treatments for neglected tropical diseases. It can assist in the formulation of future treatments that are more effective and safer.

Exploring the bio-insecticidal activity of Eucalyptus globulus essential oil/ß-cyclodextrin inclusion complexes: In vitro and in silico assessment against Ephestia kuehniella larvae.

Owing to their beneficial functional capabilities, essential oils were largely used. However, their low aqueous solubility, instability, and high volatility urged scientists to their encapsulation with cyclodextrins (CDs) to tackle their shortcomings. In this study, the co-precipitation method was used to prepare ß-CD/Eucalyptus globulus essential oil (EGEO) inclusion complexes (ICs). ß-CD/EGEO ICs were prepared at ratios (w:w) 1:2 and 1:4 with an encapsulation efficiency of 93 and 96%, respectively. The ICs characterization using the Fourier transform Infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction, Dynamic Light Scattering, and Laser Doppler Velocimetry confirmed the formation of ß-CD/EGEO ICs. The insecticidal activity of the free EGEO and ICs was explored and displayed that the complex ß-CD/EGEO 1:4 had the highest activity with the lowest LC50 against Ephestia kuehniella larvae (5.03 ± 1.16 mg/g) when compared to the free oil (8.38 ± 1.95 mg/g). Molecular docking simulations stipulated that the compound α-Bisabolene epoxide had the best docking score (ΔG = -7.4 Kcal/mol) against the selected insecticidal target α-amylase. Additionally, toxicity evaluation of the studied essential oil suggested that it could be safely used as a potent bioinsecticide as compared to chemical insecticides. This study reveals that the formation of ß-CD/EGEO ICs enhanced the oil activity and stability and could be a promising and safe tool to boost its application in food or pharmaceutical fields.

Polyaromatic Hydrocarbon Inclusion Complexes with 2-Hydroxylpropyl-ß/γ-Cyclodextrin: Molecular Dynamic Simulation and Spectroscopic Studies.

In aqueous and solid media, 2-HP-ß/γ-CD inclusion complexes with poly aromatic hydrocarbon (PAH) Phenanthrene (PHN), Anthracene (ANT), Benz(a)pyrene (BaP), and Fluoranthene (FLT) were investigated for the first time. The inclusion complexes were characterized and investigated using fluorescence and 1HNMR spectroscopy. The most prevalent complexes consisting of both guests and hosts were those with a 1:1 guest-to-host ratio. The stability constants for the complexes of PHN with 2-HP-ß-CD and 2-HP-γ-CD were 85 ± 12 M-1 and 49 ± 29 M-1, respectively. Moreover, the stability constants were found to be 502 ± 46 M-1 and 289 ± 44 M-1 for the complexes of ANT with both hosts. The stability constants for the complexes of BaP with 2-HP-ß-CD and 2-HP-γ-CD were (1.5 ± 0.02) × 103 M-1 and (9.41 ± 0.03) × 103 M-1, respectively. The stability constant for the complexes of FLT with 2-HP-ß-CD was (1.06 ± 0.06) × 103 M-1. However, FLT was observed to form a weak complex with 2-HP-γ-CD. Molecular dynamic (MD) simulations were used to investigate the mechanism and mode of inclusion processes, and to monitor the atomic-level stability of these complexes. The analysis of MD trajectories demonstrated that all guests formed stable inclusion complexes with both hosts throughout the duration of the simulation time, confirming the experimental findings. However, the flexible Hydroxypropyl arms prevented the PAHs from being encapsulated within the cavity; however, a stable exclusion complex was observed. The main forces that influenced the complexation included van der Waals interactions, hydrophobic forces, and C-H⋯π interaction, which contribute to the stability of these complexes.

Evaluation of Solubility, Dissolution Rate, and Oral Bioavailability of ß-Cyclodextrin and Hydroxypropyl ß-Cyclodextrin as Inclusion Complexes of the Tyrosine Kinase Inhibitor, Alectinib.

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with ß-cyclodextrin (ßCD) and hydroxy propyl ß-cyclodextrin (HPßCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with ßCD and HPßCD. This study identified the most soluble complex (ALB-HPßCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPßCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPßCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration.

Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various ß-cyclodextrin derivatives using advanced computational techniques and experimental validation.

Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with ß-cyclodextrin (ßCD) and its three analogs, dimethyl-ß-cyclodextrin (DMßCD), hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4',6'-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with ßCDs through two distinct orientations, with OXY/SBEßCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEßCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEßCD (2060 M-1), HPßCD (1860 M-1), DMßCD (1700 M-1), and ßCD (1420 M-1). All complexes exhibited a 1:1 binding mode (AL type), with SBEßCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMßCD, OXY/HPßCD, and OXY/SBEßCD were markedly superior compared to that of OXY alone.

Different Drug Mobilities in Hydrophobic Cavities of Host-Guest Complexes between ß-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water.

Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between ß-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between ß-CD and 5-FU. Both 1:1 and 1:2 ß-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 ß-CD/5-FU complexes, the intermolecular interactions affect the drug's mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the ß-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.

Preparation of Eudragit S100-pullulan/hydroxypropyl-ß-cyclodextrin complex-Eudragit S100 multilayer nanofiber film for resveratrol colon delivery.

Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-ß-cyclodextrin (HPßCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPßCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability, and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.

Computational Insights into Cyclodextrin Inclusion Complexes with the Organophosphorus Flame Retardant DOPO.

Cyclodextrins (CDs) were used as green char promoters in the formulation of organophosphorus flame retardants (OPFRs) for polymeric materials, and they could reduce the amount of usage of OPFRs and their release into the environment by forming [host:guest] inclusion complexes with them. Here, we report a systematic study on the inclusion complexes of natural CDs (α-, ß-, and γ-CD) with a representative OPFR of DOPO using computational methods of molecular docking, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations. The binding modes and energetics of [host:guest] inclusion complexes were analyzed in details. α-CD was not able to form a complete inclusion complex with DOPO, and the center of mass distance [host:guest] distance amounted to 4-5 Å. ß-CD and γ-CD allowed for a deep insertion of DOPO into their hydrophobic cavities, and DOPO was able to frequently change its orientation within the γ-CD cavity. The energy decomposition analysis based on the dispersion-corrected density functional theory (sobEDAw) indicated that electrostatic, orbital, and dispersion contributions favored [host:guest] complexation, while the exchange-repulsion term showed the opposite. This work provides an in-depth understanding of using CD inclusion complexes in OPFRs formulations.

The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

Exploring the formation mechanism of ferulic acid/hydroxypropyl-ß-cyclodextrin inclusion complex: spectral analyses and computer simulation.

BACKGROUND: The biological functions of ferulic acid (FA) have garnered significant interest but its limited solubility and stability have led to low bioavailability. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), with its distinctive hollow structure, offers the potential for encapsulating hydrophobic molecules. The formation of an inclusion complex between FA and HP-ß-CD may therefore be a viable approach to address the inherent limitations of FA. To investigate the underlying mechanism of the FA/HP-ß-CD inclusion complex formation, a combination of spectral analyses and computer simulation was employed. RESULTS: The disappearance of the characteristic peaks of FA in Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the formation of an inclusion complex between FA and HP-ß-CD. Thermogravimetry-derivative thermogravimetry (TG-DTG) studies demonstrated that the thermal stability of FA was enhanced due to the encapsulation of FA within HP-ß-CD. Molecular dynamics simulation also provided evidence that FA successfully penetrated the HP-ß-CD cavity, primarily driven by van der Waals interactions. The formation of the complex resulted in more compact HP-ß-CD structures. The bioavailability of FA was also strengthened through the formation of inclusion complexes with HP-ß-CD. CONCLUSIONS: The findings of this study have contributed to a deeper understanding of the interactions between FA and HP-ß-CD, potentially advancing a delivery system for FA and enhancing the bioavailability of insoluble active components. © 2024 Society of Chemical Industry.

Inclusion complexes of ß-cyclodextrin with isomeric ester aroma compounds: Preparation, characterization, mechanism study, and controlled release.

Cyclodextrins (CDs) have been discovered to provide an efficient solution to the limited application of ester aroma molecules used in food, tobacco, and medication due to their strong smell and unstable storage. This work combined molecular modeling and experimental to analyze the conformation and controlled release of isomeric ester aroma compounds/ß-CD inclusion complexes (ICs). The investigation revealed that ester aroma compounds could be effectively encapsulated within the ß-CD cavity, forming ICs with low binding affinity. Furthermore, the key driving forces in ICs were identified as hydrogen bonds and van der Waals interactions through theoretical simulation. Results from the Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and Isothermal titration calorimetry (ITC) experiments confirmed the intermolecular interaction predicted by the molecular model. Notably, the release rate of aroma compounds from L-menthyl acetate/ß-CD (LMA/ß-CD) IC exceeded that of terpinyl acetate/ß-CD (TA/ß-CD) IC. This difference is attributed to the length of the chain of aroma molecules and the variation in the position of functional groups, influencing the stable formation of ICs with ß-CD. These findings hold potential implications for refining the application of ICs across diverse industries.

Curcumin/Carrier Coprecipitation by Supercritical Antisolvent Route.

In this work, polyvinylpyrrolidone (PVP)- and ß-cyclodextrin (ß-CD)-based composite powders containing curcumin (CURC) were obtained through the supercritical antisolvent (SAS) technique. Pressure, total concentration of CURC/carrier in dimethylsulfoxide, and CURC/carrier ratio effects on the morphology and size of the precipitated powders were investigated. Using PVP as the carrier, spherical particles with a mean diameter of 1.72 µm were obtained at 12.0 MPa, 20 mg/mL, and a CURC/PVP molar ratio equal to 1/2 mol/mol; using ß-CD as the carrier, the optimal operating conditions were 9.0 MPa and 200 mg/mL; well-defined micrometric particles with mean diameters equal to 2.98 and 3.69 µm were obtained at molar ratios of 1/2 and 1/1 mol/mol, respectively. FT-IR spectra of CURC/ ß-CD inclusion complexes and coprecipitated CURC/PVP powders revealed the presence of some peaks of the active compounds. The stoichiometry of the complexes evaluated through the Job method revealed that ß-CD formed inclusion complexes with CURC at a molar ratio equal to 1/1. Dissolution profiles revealed that in comparison with the curve of the pure ingredient, the SAS-processed powders obtained using both PVP and ß-CD have an improved release rate.

Enhancing solubility and stability of piperine using ß-cyclodextrin derivatives: computational and experimental investigations.

Piperine (PP), a natural alkaloid found in black pepper, possesses significant bioactivities. However, its use in pharmaceutical applications is hindered by low water solubility and susceptibility to UV light degradation. To overcome these challenges, we investigated the potential of ß-cyclodextrin (ßCD) and its derivatives with dimethyl (DMßCD), hydroxy-propyl (HPßCD) and sulfobutyl-ether (SBEßCD) substitutions to enhance the solubility and stability of PP. This study employed computational and experimental approaches to examine the complexation between PP and ßCDs. The results revealed the formation of two types of inclusion complexes: the P-form and M-form involving the insertion of piperidine moiety and the methylene-di-oxy-phenyl moiety, respectively. These complexes primarily rely on van der Waals interactions. Among the three derivatives, the PP/SBEßCD complex exhibited the highest stability followed by HPßCD, as attributed to maximum atom contacts and minimal solvent accessibility. Solubility studies confirmed the formation of inclusion complexes in a 1:1 ratio. Notably, the stability constant of the inclusion complex was approximately two-fold higher with SBEßCD and HPßCD compared to ßCD. The DSC thermograms provided confirmation of the formation of the inclusion complex between the host and guest. These findings highlight the potential of ßCD derivatives to effectively encapsulate PP, improving its solubility and presenting new opportunities for its pharmaceutical applications.Communicated by Ramaswamy H. Sarma.

Formulation and characterization of amiodarone-methyl-beta-cyclodextrin inclusion complexes: A molecular modelling perspective.

This study aimed to develop immediate-release tablets containing amiodarone hydrochloride (AM). AM is a BCS class II compound, i.e., high permeable, and poorly soluble. The interactions between amiodarone and methyl-ß-cyclodextrin were DFT-based, theoretically measured, supporting the complexation of AM with cyclodextrin by using methyl-ß-cyclodextrin through a spray-drying process. Thus, increasing substantially the drug solubility to 93.31% and 87.14%, respectively. Solubility studies demonstrated the formation of the Drug-Methyl-ß-cyclodextrin inclusion complex with 1:1 stoichiometry. The complex formation was characterized by SBET, XRD, DSC, SEM, FTIR, and 1H NMR. Complementing, immediate-release tablets containing the inclusion complex were developed by direct compression, and in vitro dissolution studies were performed in gastrointestinal fluids using USP Pharmacopeia standard dissolution rate testing equipment. The dissolution rate of immediate-release tablets was substantially higher than the pristine drug in all mediums evaluated. These results confirm the application of methyl-ß-cyclodextrin as an effective excipient for incorporation in novel dosage forms to increase the solubility of poorly soluble drugs.

Characterization of garlic oil/ß-cyclodextrin inclusion complexes and application.

Garlic oil is a liquid extracted from garlic that has various natural antibacterial and anti-inflammatory properties and is believed to be used to prevent and treat many diseases. However, the main functional components of garlic oil are unstable. Therefore, in this study, encapsulating garlic oil with cyclodextrin using the saturated co-precipitation method can effectively improve its chemical stability and water solubility and reduce its characteristic odor and taste. After preparation, the microcapsules of garlic oil cyclodextrin were characterized, which proved that the encapsulation was successful. Finally, the results showed that the encapsulated garlic oil still had antioxidant ability and slow-release properties. The final addition to plant-based meat gives them a delicious flavor and adds texture and mouthfeel. Provided a new reference for the flavor application of garlic cyclodextrin micro-capsules in plant-based meat patties.

Rapid Study on Mefloquine Hydrochloride Complexation with Hydroxypropyl-ß-Cyclodextrin and Randomly Methylated ß-Cyclodextrin: Phase Diagrams, Nuclear Magnetic Resonance Analysis, and Stability Assessment.

This study investigates the complexation of mefloquine hydrochloride by cyclodextrins to improve its solubility in order to design an oral solution. This approach may enhance the effectiveness of mefloquine, a drug which can be used for malaria prophylaxis and treatment in children. Mefloquine hydrochloride's solubility was assessed in different buffer solutions, and its quantification was achieved through high-performance liquid chromatography. The complexation efficiency with cyclodextrins was evaluated, and nuclear magnetic resonance (NMR) methods were employed to determine the interactions between mefloquine and cyclodextrins. Mefloquine's solubility increased when combined with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and randomly methylated ß-cyclodextrin (RAMEB), with RAMEB being more effective. The drug's solubility varied across different pH buffers, being higher in acidic buffers. Interestingly, mefloquine's solubility decreased with a citrate buffer, possibly due to precipitation. The NMR studies highlighted non-covalent interactions between RAMEB, HP-ß-CD, and mefloquine, explaining the solubilizing effect via complexation phenomena. Furthermore, the NMR experiments indicated the complexation of mefloquine by all the studied cyclodextrins, forming diastereoisomeric complexes. Cyclodextrin complexation improved mefloquine's solubility, potentially impacting its bioavailability.

Effects of Encapsulation of Caesalpinia sappan L. with Cyclodextrins for Bovine Mastitis.

The main components of Caesalpinia sappan L. (CS) are brazilin and brazilein, which show high potential in pharmacologic applications. However, these have been drastically limited by the poor water solubility and stability. The present study investigates the formation of inclusion complexes F1, F2, and F3 between CS and ß-cyclodextrin (ßCD), hydroxypropyl-ß-cyclodextrin (HPßCD), and methyl-ß-cyclodextrin (MßCD), respectively. These complexes were characterized by Fourier transform infrared spectroscopy (FT-IR). The results showed that the highest encapsulation efficiency and loading capacity of CS extract were 44.24% and 9.67%, respectively. The solubility and stability of CS extract were significantly increased through complexation in phase solubility and stability studies. The complexes F1-F3 showed mainly significant antibacterial activities on gram-positive bacteria pathogens causing mastitis. Moreover, the expression levels of COX-2 and iNOS were significantly decreased in LPS-induced inflammatory cells at concentrations of 50 and 100 µg/mL. In addition, treatment of complex F3 (CS/MßCD) in bovine endothelial cells remarkably increased the chemokine gene expression of CXCL3 and CXCL8, which were responsible for immune cell recruitment (9.92 to 11.17 and 8.23 to 9.51-fold relative to that of the LPS-treated group, respectively). This study provides a complete characterization of inclusion complexes between CS extract and ßCD, HPßCD, and MßCD for the first time, highlighting the impact of complex formation on the pharmacologic activities of bovine mastitis.

Curcuminoids-enriched extract and its cyclodextrin inclusion complexes ameliorates arthritis in complete Freund's adjuvant-induced arthritic mice via modulation of inflammatory biomarkers and suppression of oxidative stress markers.

Curcuma longa extract and its marker curcuminoids have potential use in inflammatory conditions. However, curcuminoids solubility and bioavailability are major hindrances to their bioactivity. The current study investigated green extraction-based curcuminoids-enriched extract (CRE) prepared from C. longa and its cyclodextrin inclusion complexes, i.e., binary inclusion complexes (BC) and ternary inclusion complexes (TC), in complete Freund's adjuvant (CFA)-induced mice for their comparative anti-arthritic efficacy. CRE, BC, and TC (2.5 and 5 mg/kg) with the standard drug diclofenac sodium (13.5 mg/kg) were orally administered to mice for 4 weeks. Variations in body weight, hematological and biochemical parameters, along with gene expression analysis of arthritis biomarkers, were studied in animals. The histopathological analysis and radiographic examination of joints were also performed. CRE, BC and TC treatment significantly restored the arthritic index, histopathology and body weight changes. The concentration of C-reactive protein, rheumatoid factor and other liver function parameters were significantly recovered by curcuminoids formulations. The pro-inflammatory cytokines (NF-κB, COX-2, IL-6, IL-1ß, and TNF-α) gene expression was considerably (p < 0.001) downregulated, while on the other side, the anti-inflammatory genes IL-4 and IL-10 were upregulated by the use of CRE and its complexes. The concentration of antioxidant enzymes was considerably (P < 0.001) recovered by CRE, BC and TC with marked decrease in lipid peroxidation, erosion of bone, inflammation of joints and pannus formation in comparison to arthritic control animals. Therefore, it is concluded that green CRE and its cyclodextrin formulations with enhanced solubility could be considered as an applicable therapeutic choice to treat chronic polyarthritis.

Revisiting the Formation of Starch-Monoglyceride-Protein Complexes: Effects of Octenyl Succinic Anhydride Modification.

Starch-lipid-protein complexes are attracting increasing attention due to their unique structure and low enzymatic digestibility. However, the mechanisms underlying the formation of these ternary complexes, especially those with monoglycerides as the lipid component, remain unclear. In the present study, potato starch or octenyl succinic anhydride (OSA)-modified potato starch (OSAPS), various monoglycerides (MGs), and beta-lactoglobulin (ßLG) were used in model systems to characterize the formation, structure, and in vitro digestibility of the respective ternary complexes. Colorimetry and live/dead staining assays demonstrated that the OSAPS had good biocompatibility. Experimental data and molecular dynamics simulations showed that both unmodified potato starch and OSAPS formed starch-lipid-protein complexes with MGs and ßLG. Of the two types of starch, OSA formed a greater amount of the more stable type II V-crystallites in complexes, which had greater resistance to in vitro enzymic digestion. This study demonstrated for the first time that starch can interact with MGs and ßLG to form ternary complexes and that OSA esterification of starch promoted the formation of more complexes than unmodified starch.