Enhanced antibacterial and anti-quorum sensing activities of triclosan by complexation with modified β-cyclodextrins

Triclosan (TCS), an antimicrobial agent widely used in consumer and medical products, was complexed with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD). Phase-solubility studies indicated that inclusion complexes of 1:1 stoichiometry were formed and allowed estimation of the associated equilibrium constants and free-energy changes. At the highest cyclodextrin concentrations investigated, an almost 20-fold increase in the apparent water solubility of TCS was determined. Susceptibility tests against Escherichia coli and Staphylococcus aureus showed that the TCS–HPβCD and TCS–MβCD complexes exhibited antibacterial properties higher than those of uncomplexed TCS. The two complexes were also found capable of interfering with cell-to-cell communication mechanisms in the C. violaceum model system relying on N-acylhomoserine lactone autoinducers. The inhibitory activity of TCS increased significantly upon inclusion of the drug in HPβCD or MβCD, with small differences between the two CDs. The results obtained suggest that the investigated complexes could be used for treating infections caused by TCS-susceptible pathogens or for preventing biofilm formation on indwelling medical devices such as catheters, stents and orthopedic implants.     

Studies on 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole/2-hydroxypropyl-β-cyclodextrin association: Characterization, molecular modeling studies, and in vivo anthelminthic activity

The purpose of this work is to study the molecular association that occurs between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic compound recently found by our research group, with poor aqueous solubility. The complex stability constant and stoichiometric ratio determined by phase-solubility diagram and Job's plot provided evidence that HPβCD enhanced water solubility of RCB20 through inclusion complex formation. Two-dimensional 1H NMR spectroscopy is used to study the molecular arrangement of inclusion complex in solution. These results are further supported using molecular modeling studies. In the solid state, the complexation is confirmed by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy. Finally, RCB20/HPβCD complex has better activity than RCB20 against the adult and muscle larvae phase of Trichinella spiralis.     

Binary and ternary inclusion complexes of finasteride in HPβCD and polymers: Preparation and characterization

The aim of this study was to determine whether inclusion complexes between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and finasteride (FIN) are formed, and to characterize these. Equimolar FIN/HPβCD solid systems in the presence or absence of 0.1% (w/v) of polyvinylpyrrolidone K30 (PVP K30) or 0.3% of chitosan were prepared by coevaporation and freeze-drying methods. The systems were characterized by phase solubility, NMR, DSC, and XRD analysis. The results suggest that true binary and ternary inclusion complexes were formed.     

Multiple complexation of cyclodextrin with soy isoflavones present in an enriched fraction

In the present study we evaluated the complexation of daidzein/genistein/glycitein, present in an isoflavone enriched fraction (IEF), with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin (HPβCD). Based on the increased solubility and higher complexation efficiency, IEF and HPβCD solid complexes were prepared by kneading, freeze-drying, co-evaporation, spray-drying and microwave. The solid complexes were characterized using Fourier transformed-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and nuclear magnetic resonance spectroscopy, and the isoflavone content and solubility were determined by liquid chromatography. The results suggest that the isoflavones daidzein, genistein and glycitein may be externally associated to HPβCD as well as that isoflavones/HPβCD inclusion complexes are formed through the insertion of B-ring into the cyclodextrin cavity. Except for the freeze-dried IEF/HPβCD solid complex, all complexes showed similar content and solubility. In conclusion, the three isoflavones showed to be able to simultaneously complex with HPβCD.     

A 5,7-Dimethoxyflavone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex with Anti-Butyrylcholinesterase Activity

This study aimed to improve the water solubility of 5,7-dimethoxyflavone (5,7-DMF) isolated from Kaempferia parviflora by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβ-CD). The phase solubility profile of 5,7-DMF in the presence of HPβ-CD was classified as A_L-type and indicated a 1:1 mole ratio. Differential scanning colorimetry, X-ray diffraction, NMR and SEM analyses supported the formation of a 5,7-DMF/HPβ-CD inclusion complex involving the A ring of 5,7-DMF inside the HPβ-CD cavity. This is the first example of CD inclusion with the A ring of non-hydroxyl flavones. The stability and binding constants of the complexes were determined using the phase solubility and UV-vis absorption spectroscopy, respectively. The water solubility of 5,7-DMF was increased 361.8-fold by complexation with HPβ-CD and overcame the precipitation problem observed in aqueous buffers, such as during in vitro anti-butyrylcholinesterase activity assays. The 1:1 mole ratio of the 5,7-DMF/HPβ-CD complex showed a 2.7-fold higher butyrylcholinesterase inhibitory activity (in terms of the IC₅₀ value) compared to the non-complexed compound.     

Cyclodextrin inclusion complex to improve physicochemical properties of herbicide bentazon: exploring better formulations

The knowledge of the host-guest complexes using cyclodextrins (CDs) has prompted an increase in the development of new formulations. The capacity of these organic host structures of including guest within their hydrophobic cavities, improves physicochemical properties of the guest. In the case of pesticides, several inclusion complexes with cyclodextrins have been reported. However, in order to explore rationally new pesticide formulations, it is essential to know the effect of cyclodextrins on the properties of guest molecules.In this study, the inclusion complexes of bentazon (Btz) with native βCD and two derivatives, 2-hydroxypropyl-β-cyclodextrin (HPCD) and sulfobutylether-β-cyclodextrin (SBECD), were prepared by two methods: kneading and freeze-drying, and their characterization was investigated with different analytical techniques including Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), X-ray diffractometry (XRD) and differential pulse voltammetry (DPV). All these approaches indicate that Btz forms inclusion complexes with CDs in solution and in solid state, with a stoichiometry of 1∶1, although some of them are obtained in mixtures with free Btz. The calculated association constant of the Btz/HPCD complex by DPV was 244±19 M(-1) being an intermediate value compared with those obtained with βCD and SBECD. The use of CDs significantly increases Btz photostability, and depending on the CDs, decreases the surface tension. The results indicated that bentazon forms inclusion complexes with CDs showing improved physicochemical properties compared to free bentazon indicating that CDs may serve as excipient in herbicide formulations.     

Triamcinolone solubilization by (2-hydroxypropyl)-β-cyclodextrin: A spectroscopic and computational approach

The molecular foundations of the use of (2-hydroxypropyl)-β-cyclodextrin (HPβCD) as solubility promoter of triamcinolone acetonide (TrA), a corticosteroid with very low aqueous solubility, was investigated by a multidisciplinary spectroscopic and computational approach. Aqueous solutions of TrA and HPβCD were investigated by UV and NMR spectroscopies. The association constant was determined by phase solubility diagrams and by the Foster-Fyfe method whereas the nature of the drug/cyclodextrin aggregates was probed by using the NMR DOSY technique. ROE measurements in solution led to stereochemical information regarding the nature of inclusion processes. TrA/HPβCD powders were prepared and investigated by Raman spectroscopy supported by computational methods. A molecular interaction of the hydroxyacyl chain with cyclodextrin, not identified in solution, was detected. Raman imaging experiments confirmed the attainment of a molecularly homogeneous system when the TrA/HPβCD molar ratio was 1:7 whereas TrA crystallized for mixtures richer in TrA (1:3.5) forming domains with size in the range of 10-15μm. We demonstrate that the combined use of several spectroscopical techniques with specific responsivities allows a detailed depiction of drug/cyclodextrin interaction useful in the development of novel pharmaceutical formulation.     

Physicochemical and biological properties of 2-O-α-D-galactosyl-cyclomaltohexaose (α-cyclodexterin) and -cyclomaltoheptaose (β-cyclodextrin)

The physicochemical and biological properties of the new branched cyclomaltooligosaccharides (cyclodextrins; CDs), 2-O-α-D-galactosyl-cyclomaltohexaose (2-O-α-D-galactosyl-α-cyclodextrin, 2-Gal-αCD) and 2-O-α-D-galactosyl-cyclomaltoheptaose (2-O-α-D-galactosyl-β-cyclodextrin, 2-Gal-βCD), were investigated. The formation of inclusion complexes of 2-Gal-CDs with various kinds of guest compounds (clofibrate, cholesterol, cholecalciferol, digitoxin, digitoxigenin, and prostaglandin A(1)) was examined by a solubility method, and the results were compared with those of non-branched CDs and other 6-O-glycosyl-CDs such as 6-O-α-D-galactosyl-CDs, 6-O-α-D-glucosyl-CDs, and 6-O-α-maltosyl-CDs. The inclusion abilities of 2-Gal-αCD for clofibrate and prostaglandin A(1), and 2-Gal-βCD for clofibrate, cholecalciferol, cholesterol, and digitoxigenin were markedly weaker than those of non-branched CD and other 6-O-glycosyl-CDs in each series, probably because of a steric hindrance caused by the α-(1→2)-galactoside linkage. The hemolytic activities of 2-Gal-CDs on human erythrocytes were the lowest among each CD series, and the compounds showed negligible cytotoxicity towards Caco-2 cells up to at least 100mM.     

Molecular Modeling-Based Inclusion Mechanism and Stability Studies of Doxycycline and Hydroxypropyl-β-Cyclodextrin Complex for Ophthalmic Delivery

The aim of the present study was to prepare a stable complex of doxycycline (Doxy) and hydroxypropyl-β-cyclodextrin (HPβCD) for ophthalmic delivery and investigate the inclusion mechanism and the inclusion effects on the stability of Doxy. The Doxy/HPβCD complex was prepared by solution stirring and then characterized by scanning electron microscopy and ultraviolet spectroscopy. Based on results of nuclear magnetic resonance, molecular model of Doxy/HPβCD complex was established using computational simulation of PM3 method implemented in Gaussian 03. Stabilities of Doxy/HPβCD complex in both aqueous solution and solid state at 25°C were evaluated by HPLC. Finally, in vitro antibacterial activity of the Doxy/HPβCD complex was evaluated by disk diffusion test. It was found that the stabilities of Doxy/HPβCD complex in both aqueous solution and solid state were improved obviously as compared with Doxy alone. This stability enhancement is consistent with the inclusion mechanism between HPβCD and Doxy, which showed that the unstable site of Doxy molecule at 6-CH₃ was protected in the hydrophobic cavity of HPβCD, additionally, the chelation of Mg²⁺ provided a synergetic protection of the other unstable site of Doxy at 4-N(CH₃)₂. The antibacterial activity results indicated that Doxy/HPβCD complex might have potential for clinical applications.     

Physicochemical and biological properties of 2-O-α-d-galactosyl-cyclomaltohexaose (α-cyclodexterin) and -cyclomaltoheptaose (β-cyclodextrin)

The physicochemical and biological properties of the new branched cyclomaltooligosaccharides (cyclodextrins; CDs), 2-O-α-d-galactosyl-cyclomaltohexaose (2-O-α-d-galactosyl-α-cyclodextrin, 2-Gal-αCD) and 2-O-α-d-galactosyl-cyclomaltoheptaose (2-O-α-d-galactosyl-β-cyclodextrin, 2-Gal-βCD), were investigated. The formation of inclusion complexes of 2-Gal-CDs with various kinds of guest compounds (clofibrate, cholesterol, cholecalciferol, digitoxin, digitoxigenin, and prostaglandin A₁) was examined by a solubility method, and the results were compared with those of non-branched CDs and other 6-O-glycosyl-CDs such as 6-O-α-d-galactosyl-CDs, 6-O-α-d-glucosyl-CDs, and 6-O-α-maltosyl-CDs. The inclusion abilities of 2-Gal-αCD for clofibrate and prostaglandin A₁, and 2-Gal-βCD for clofibrate, cholecalciferol, cholesterol, and digitoxigenin were markedly weaker than those of non-branched CD and other 6-O-glycosyl-CDs in each series, probably because of a steric hindrance caused by the α-(1→2)-galactoside linkage. The hemolytic activities of 2-Gal-CDs on human erythrocytes were the lowest among each CD series, and the compounds showed negligible cytotoxicity towards Caco-2 cells up to at least 100 mM.     

Effects of an antimalarial quinazoline derivative on human erythrocytes and on cell membrane molecular models

Plasmodium, the parasite which causes malaria in humans multiplies in the liver and then infects circulating erythrocytes. Thus, the role of the erythrocyte cell membrane in antimalarial drug activity and resistance has key importance. The effects of the antiplasmodial N(6)-(4-methoxybenzyl)quinazoline-2,4,6-triamine (M4), and its inclusion complex (M4/HPβCD) with 2-hydroxypropyl-β-cyclodextrin (HPβCD) on human erythrocytes and on cell membrane molecular models are herein reported. This work evidences that M4/HPβCD interacts with red cells as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a 10μM concentration; b) in isolated unsealed human erythrocyte membranes (IUM) a concentration as low as 1μM induced sharp DPH fluorescence anisotropy decrease whereas increasing concentrations produced a monotonically decrease of DPH fluorescence lifetime at 37°C; c) X-ray diffraction studies showed that 200μM induced a complete structural perturbation of dimyristoylphosphatidylcholine (DMPC) bilayers whereas no significant effects were detected in dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of lipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively; d) fluorescence spectroscopy data showed that increasing concentrations of the complex interacted with the deep hydrophobic core of DMPC large unilamellar vesicles (LUV) at 18°C. All these experiments are consistent with the insertion of M4/HPβCD in the outer monolayer of the human erythrocyte membrane; thus, it can be considered a promising and novel antimalarial agent.     

Spectroscopic characterization of the inclusion complexes of luteolin with native and derivatized β-cyclodextrin

The inclusion complexes of Luteolin (LU) with cyclodextrins (CDs) including β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD) and dimethyl-β-cyclodextrin (DMβCD), Scheme 1, have been investigated using the method of steady-state fluorescence. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was obtained in the case of HPβCD followed by DMβCD and βCD. Moreover, ¹H NMR and 2D NMR were carried out, revealing that LU has different form of inclusion which is in agreement with molecular modeling studies. These models confirm that when LU–βCD and LU–DMβCD complexes are formed, the B-ring is oriented toward the primary rim; however, for LU–HPβCD complex this ring is oriented toward the secondary rim. The ESR results showed that the antioxidant activity of luteolin was the order LU–HPβCD > LU–DMβCD > LU–βCD > LU, hence the LU-complexes behave are better antioxidants than luteolin free.     

Methyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK

The drug 2-hydroxypropyl-β-cyclodextrin (HPβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease, type C (NPC) and has been advanced to human clinical trials. However, its mechanism of action for reducing cholesterol accumulation in NPC cells is uncertain and its molecular target is unknown. We found that methyl-β-cyclodextrin (MβCD), a potent analog of HPβCD, restored impaired macroautophagy/autophagy flux in Niemann-Pick disease, type C1 (NPC1) cells. This effect was mediated by a direct activation of AMP-activated protein kinase (AMPK), an upstream kinase in the autophagy pathway, through MβCD binding to its β-subunits. Knockdown of PRKAB1 or PRKAB2 (encoding the AMPK β1 or β2 subunit) expression and an AMPK inhibitor abolished MβCD-mediated reduction of cholesterol storage in NPC1 cells. The results demonstrate that AMPK is the molecular target of MβCD and its activation enhances autophagy flux, thereby mitigating cholesterol accumulation in NPC1 cells. The results identify AMPK as an attractive target for drug development to treat NPC.     

SN-38-Cyclodextrin Complexation and Its Influence on the Solubility,Stability, and In Vitro Anticancer Activity Against Ovarian Cancer

SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether β-cyclodextrin (SBEβCD), hydroxypropyl β-cyclodextrin, randomly methylated β-cyclodextrin, and methyl β-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-βCD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBEβCD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an A_P-type system. Aqueous solubility of SN-38 was enhanced by about 30–1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBEβCD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBEβCD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBEβCD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications.     

The aqueous solubility and thermal stability of α-lipoic acid are enhanced by cyclodextrin

We investigated the effects of various cyclodextrins (CDs) on the aqueous solubility and thermal stability of α-lipoic acid, a compound with low water solubility. α-CD, β-CD, and γ-CD had little effect on the aqueous solubility of α-lipoic acid. In contrast, 6-O-α-maltosyl-CDs increased it in a concentration-dependent manner, 6-O-α-maltosyl-β-CD enhancing solubility the most. The thermal stability of α-lipoic acid in the solid state was improved by the addition of G2-β-CD(?), a commercial product of 6-O-α-maltosyl-β-CD. The thermal stability of α-lipoic acid was also improved by the addition of β-CD. Analysis by differential scanning calorimetry showed that G2-β-CD(?), a mixture of maltosyl-β-CDs, and β-CD efficiently formed complexes with α-lipoic acid. These results suggest that the sizes and shapes of these β-CD compounds are compatible with complexation with α-lipoic acid. Moreover, both the formation of an aqueous complex with G2-β-CD(?) and an insoluble complex with β-CD increased the thermal stability of α-lipoic acid.     

Physicochemical and molecular modeling studies of cefixime–l-arginine–cyclodextrin ternary inclusion compounds

In an attempt to improve the physicochemical properties of cefixime (CEF), its supramolecular inclusion compounds were prepared with β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) in presence and/or absence of ternary component l-arginine (ARG) using spray drying technique. Initially, the phase solubility studies revealed a stoichiometry of 1:1 molar ratio with an A_L-type of phase solubility curve. The stability constants of binary systems were remarkably improved in presence of ARG, indicating positive effect of its addition. The inclusion complexes were characterized by FTIR, XRPD, DSC, SEM, particle size analysis, and dissolution studies. Further, molecular mechanic (MM) calculations were performed to investigate the possible orientations of CEF inside βCD cavity in presence and/or absence of ternary component. In case of physicochemical studies, the ternary systems performed well as a result of comprehensive effect of ternary complexation and particle size reduction achieved by a spray drying technology.     

Physicochemical Characterization of Berberine Chloride: A Perspective in the Development of a Solution Dosage Form for Oral Delivery

The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride–HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.KEY WORDS: berberine chloride, complexation, cyclodextrin, solubility, surfactants     

Enhancement of rhubarb extract solubility and bioactivity by 2-hydroxypropyl-β-cyclodextrin

Rhubarb is a traditional Chinese medicinal herb, and the ethanolic extract of rhubarb consists of active anthraquinones, which are hydrophobic and have antiproliferative effects on hepatoma cell lines. To increase the aqueous solubility of rhubarb and study the consequent bioavailability, the ethanolic extract of rhubarb was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a cyclic oligosaccharide that has a hydrophilic outer surface and a hydrophobic central cavity, to form a rhubarb–HP-β-CD complex. This complex was characterized by performing nuclear magnetic resonance spectroscopy, two-dimensional rotating frame spectroscopy and thin layer chromatography to confirm the inclusion of anthraquinones from rhubarb extract in HP-β-CD (weight ratio of rhubarb extract:HP-β-CD = 1:9). We investigated the effects of complexing rhubarb extract with HP-β-CD on the growth of Huh7 and HepG2 cells by performing cytotoxicity analysis, cellular uptake test, and colony formation assay. Our results showed that complexation of rhubarb extract with HP-β-CD increased the aqueous solubility and bioavailability of rhubarb and thus enhanced its effect on hepatoma cells.     

Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol

Carvedilol (CAR) is a non-selective α and β blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-β-cyclodextrin (HPβCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPβCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPβCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPβCD and PLX/PVP on water solubility and bioavailability of CAR.