Ternary Inclusion Complexes Research Articles

Binary and Ternary Inclusion Complexes of Niflumic Acid: Synthesis, Characterization, and Dissolution Profile.

Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug-cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.

Molecular Insight into the Ternary Complex Formation between Ethambutol, Isoniazid and β‐Cyclodextrin

AbstractLong term intake of antituberculosis drugs will lead to severe adverse reactions that will ultimately deteriorate a patient's health and well‐being. With that, the ternary inclusion complex was explored, whereby β‐cyclodextrin (β‐CD) was chosen as the supramolecular host carrier to accommodate two kinds of first line antituberculosis guest drug molecules simultaneously, namely isoniazid (INH) and ethambutol (ETB) which would provide many therapeutic benefits. The inclusion complex of β‐CD/INH/ETB was prepared using solvent evaporation method. Fourier transform infrared spectroscopy (FT‐IR), proton nuclear magnetic resonance spectroscopy (1H‐NMR), and 2‐dimensional nuclear Overhauser effect spectroscopy (2D‐NOESY) NMR were used to investigate the functional groups and structure of the complex. Scanning electron microscopy (SEM) and X‐ray diffraction (XRD) were employed to study the surface morphology and crystallinity changes during complex formation. Thermogravimetric analysis (TGA) was performed to investigate the thermal properties of the complex. FT‐IR and both types of NMR results had revealed the successful penetration of both the drug molecules into the β‐CD cavity. SEM images and XRD spectra had shown a drastic change in surface structure and reduction in crystallinity during complex formation, which had indicated successful formation of a new compound. TGA had proven that the complex had significantly greater thermal stability as compared to the pure components. Molecular dynamics (MD) and molecular docking simulations were also performed to understand the molecular interaction between β‐CD, INH, and ETB. Through precise calculations of interaction and binding energies, β‐CD/INH/ETB was found to be a more stable inclusion complex compared to the binary β‐CD/INH and β‐CD/ETB complexes.

Febuxostat ternary inclusion complex using SBE7-βCD in presence of a water-soluble polymer: physicochemical characterization, in vitro dissolution, and in vivo evaluation

Febuxostat (FBX), a potent xanthine oxidase inhibitor, is widely used as a blood uric acid-reducing agent and has recently shown a promising repurposing outcome as an anti-cancer. FBX is known for its poor water solubility, which is the main cause of its weak oral bioavailability. In a previous study, we developed a binary system complex between FBX and sulfobutylether-β-cyclodextrin (SBE7-βCD) with improved dissolution behavior. The aim of the current study was to investigate the effect of incorporating a water-soluble polymer with a binary system forming a ternary one, on further enhancement of FBX solubility and dissolution rate. In vivo oral bioavailability was also studied using LC–MS/MS chromatography. The polymer screening study revealed a marked increment in the solubility of FBX with SBE7-βCD in the presence of 5% w/v polyethylene glycol (PEG 6000). In vitro release profile showed a significant increase in the dissolution rate of FBX from FBX ternary complex (FTC). Oral in vivo bioavailability of prepared FTC showed more than threefold enhancement in Cmax value (17.05 ± 2.6 µg/mL) compared to pure FBX Cmax value (5.013 ± 0.417 µg/mL) with 257% rise in bioavailability. In conclusion, the association of water-soluble polymers with FBX and SBE7-βCD system could significantly improve therapeutic applications of the drug.Graphical

Preparation, characterization and evaluation of cefixime ternary inclusion complexes formated by mechanochemical strategy

Preparation, characterization and evaluation of cefixime ternary inclusion complexes formated by mechanochemical strategy

Microwave-Assisted Formation of Ternary Inclusion Complex of Pterostilbene.

Pterostilbene (PTS) is a naturally occurring phytoalexin. PTS displays limited water solubility, which consequently results in its diminished oral bioavailability. Therefore, a ternary inclusion complex (TIC) of PTS with β-cyclodextrin (βCD) in the presence of ternary substance Pluronic® F-127 (PLF) was prepared using microwave technology. The PTS-TIC was characterized by dissolution performance. Further, the prepared TIC was characterized by DSC, FTIR, NMR, XRD, and SEM analysis. Additionally, the antioxidant activity of PTS and PTS-TIC was also evaluated. Phase-solubility studies revealed that PTS's solubility in water was increased by 6.72 times when βCD/PLF was present. In comparison with PTS, prepared PTS-TIC produced a considerable improvement in PTS release. After 1 h, 74.03 ± 4.47% of PTS was released from PTS-TIC. Outcomes of DSC, FTIR, NMR, XRD, and SEM analysis revealed that the PTS was enclosed in the βCD cavity. In terms of antioxidant properties, the PTS-TIC formulation demonstrated superior activity compared to PTS, possibly attributed to the improved solubility of PTS resulting from the formation of TIC using microwave technology. It was concluded that microwave technology proved to be an extremely beneficial means of interacting PTS with βCD. In addition to increasing the solubility of PTS, the findings are also expected to improve its bioavailability by increasing its solubility. As a result, this study could provide insight into potential methods for enhancing the solubility of polyphenolic substances like PTS.

Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

Continuous Manufacturing of Solvent-Free Cyclodextrin Inclusion Complexes for Enhanced Drug Solubility via Hot-Melt Extrusion: A Quality by Design Approach.

Conventional cyclodextrin complexation enhances the solubility of poorly soluble drugs but is solvent-intensive and environmentally unfavorable. This study evaluated solvent-free hot-melt extrusion (HME) for forming cyclodextrin inclusion complexes to improve the solubility and dissolution of ibuprofen (IBU). Molecular docking confirmed IBU's hosting in Hydroxypropyl-β-cyclodextrin (HPβ-CD), while phase solubility revealed its complex stoichiometry and stability. In addition, an 11 mm twin-screw co-rotating extruder with PVP VA-64 as an auxiliary substance aided the complex formation and extrusion. Using QbD and the Box-Behnken design, we studied variables (barrel temperature, screw speed, and polymer concentration) and their impact on solubility and dissolution. The high polymer concentration and high screw speeds positively affected the dependent variables. However, higher temperatures had a negative effect. The lowest barrel temperature set near the Tg of the polymer, when combined with high polymer concentrations, resulted in high torques in HME and halted the extrusion process. Therefore, the temperature and polymer concentration should be selected to provide sufficient melt viscosities to aid the complex formation and extrusion process. Studies such as DSC and XRD revealed the amorphous conversion of IBU, while the inclusion complex formation was demonstrated by ATR and NMR studies. The dissolution of ternary inclusion complexes (TIC) produced from HME was found to be ≥85% released within 30 min. This finding implied the high solubility of IBU, according to the US FDA 2018 guidance for highly soluble compounds containing immediate-release solid oral dosage forms. Overall, the studies revealed the effect of various process parameters on the formation of CD inclusion complexes via HME.

Enhanced Solubility and Stability of Aripiprazole in Binary and Ternary Inclusion Complexes Using Hydroxy Propyl Beta Cyclodextrin (HPβCD) and L-Arginine.

The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPβCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development.

Preparation and Spectroscopic Characterization of Ternary Inclusion Complexes of Ascorbyl Palmitate and Urea with γ-Cyclodextrin

A three-component inclusion complex of ascorbyl palmitate (ASCP), urea (UR), and γ-cyclodextrin (γCD) with a molar ratio of 1/12 has been prepared for the first time using the evaporation method (EVP method) and the grinding and mixing method (GM method). Also, we investigated changes in the physicochemical properties of the three-component complexes. The powder X-ray diffraction (PXRD) measurements showed ASCP, UR, and γCD characteristic peaks in the physical mixture (PM) (AU (ASCP/UR = 1/12)/γCD = 1/2). In GM (AU (ASCP/UR = 1/12)/γCD = 1/1), new diffraction peaks were observed around 2θ = 7.5° and 16.6°, while characteristic peaks derived from EVP (ASCP/UR = 1/12) were observed at 2θ = 23.4° and 24.9°. On the other hand, new diffraction peaks at 2θ = 7.4° and 16.6° were observed in GM (1/2). In the differential scanning calorimeter (DSC) measurement, an endothermic peak at around 83 °C was observed in the GM (1/1) sample, which is thought to originate from the phase transition of urea from the hexagonal to the tetragonal form. An endothermic peak around 113.9 °C was also observed for EVP (ASCP/UR = 1/12). However, no characteristic phase transition-derived peak or EVP (ASCP/UR = 1/12)-derived endothermic peak was observed in GM (1/2). Near infrared (NIR) spectroscopy of GM (1/2) showed no shift in the peak derived from the CH group of ASCP. The peaks derived from the NH group of UR shifted to the high and low wavenumber sides at 5032 cm−1 and 5108 cm−1 in EVP (ASCP/UR = 1/12). The peak derived from the OH group of γCD shifted, and the peak derived from the OH group of ASCP broadened at GM (1/2). These results suggest that AU (ASCP/UR = 1/12)/γCD prepared by the mixed grinding method formed inclusion complexes at the molar ratio (1/2).

Ternary Inclusion Complex of Sinapic Acid with Hydroxypropyl-β-cyclodextrin and Hydrophilic Polymer Prepared by Microwave Technology

Sinapic acid (SA) is a poorly water-soluble substance which could result in poor bioavailability. The aim of this study was to determine the “hydroxypropyl β-cyclodextrin (HPβCD)” solubilization of SA in the presence of the auxiliary substance hydroxypropyl methylcellulose (HPMC) and to evaluate the ternary inclusion complex prepared by microwave technology. Phase-solubility profiles showed that HPβCD exhibited the greatest solubilizing effect on SA in the presence of HPMC. The enhanced rate of SA dissolution was exhibited by a ternary complex. Outcomes of analyses such as “DSC, FTIR, NMR, and SEM” confirmed the embedding of SA into the cavity of the HPβCD and the formation of a ternary inclusion complex. The outcomes of antioxidant activity (ABTS and nitric oxide scavenging activity) demonstrated that SA ternary inclusion complex (TIC) presented strong antioxidant activity, which might be a result of the enhanced solubility of SA in the TIC prepared by microwave technology. Hence, SA-TIC formulation could be a better dosage form which may protect the body from free radical damage and oxidative stress. Microwave technology greatly boosted the interaction of SA with HPβCD and HPMC, and such findings are expected to contribute to raising the solubility of SA, thereby improving the bioavailability of SA.

Formulation of Multicomponent Chrysin-Hydroxy Propyl β Cyclodextrin-Poloxamer Inclusion Complex Using Spray Dry Method: Physicochemical Characterization to Cell Viability Assessment.

The work aimed to enhance chrysin (CHR) water solubility, dissolution, and in vitro antibacterial as well as cell viability. Chrysin binary, as well as ternary inclusion complex, were prepared using the spray drying method. The influence of an auxiliary component (poloxamer; PLX) was also assessed after being incorporated into the chrysin HP βCD complex (CHR-BC) and formed as a chrysin ternary complex (CHR-TC). The phase solubility investigation was carried out in order to assess the complexation efficiency and stability constant. The samples were assessed for the dissolution test, physicochemical evaluation, antibacterial activity, and cell viability tests were also assessed. The results of the phase solubility investigation showed that the stability constant for the binary system (268 M-1) was lower than the ternary system (720 M-1). The complex stability was validated by the greater stability constant value. The dissolution results showed that pure CHR had a limited release of 32.55 ± 1.7% in 60 min, while prepared CHR-TC and CHR-BC both demonstrated maximum CHR releases of 99.03 ± 2.34% and 71.95 ±2.1%, respectively. The dissolution study's findings revealed that the release of CHR was much improved over that of pure CHR. A study using a scanning electron microscope showed that CHR-TC contains more agglomerated and amorphous components. The higher conversion of crystalline CHR into an amorphous form is responsible for the structural alterations that are observed. After complexation, the distinctive peaks of pure CHR changed due to the complexation with HP βCD and PLX. The antimicrobial and cell viability results revealed improved antimicrobial activity as well as a lower IC50 value than pure CHR against the tested anticancer cell line (MCF7).

From Induced-Fit Assemblies to Ternary Inclusion Complexes with Fullerenes in Corannulene-Based Molecular Tweezers.

The participation of the tether moiety in fullerene recognition of corannulene-based molecular tweezers is known to be an important factor. In the present work, we describe the synthesis of a set of fullerene receptors bearing two corannulene units located at a suitable distance to effectively interact with C60 and C70. The tether comprises a fluorene-like scaffold where an assortment of different groups with variable electronic properties has been grafted. The photophysical and electrochemical properties of all final compounds have been unveiled and correlated to the donor/acceptor (DA) nature of the tether. Despite these strong variations, their affinity toward fullerenes cannot be correlated in any way to simple DA behavior as the main contribution to the interaction correspond to London dispersion forces. We found, however, that the sulfur-derived subfamily is able to adapt better to the fullerene outer surface slightly increasing the charge transfer and electrostatic attractive interactions being the most outstanding example the case of thiophene 4-S with C70 as it is capable of forming a ternary 2:1 inclusion complex in solution with an electronic binding energy that offsets entropy and desolvation penalties typically associated with higher-order inclusion complexes.

The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson's disease animal model.

Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1mg/kg haloperidol daily intraperitoneally, for 3weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30mg/kg, L-dopa and carbidopa (100 + 25mg/kg) were orally administered on each day for 3weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.

Formulating Ternary Inclusion Complex of Sorafenib Tosylate Using β-Cyclodextrin and Hydrophilic Polymers: Physicochemical Characterization and In Vitro Assessment.

Sorafenib tosylate (SFNT) is the first-line drug for hepatocellular carcinoma. It exhibits poor solubility leading to low oral bioavailability subsequently requiring intake of large quantities of drug to exhibit desired efficacy. The present investigation was aimed at enhancing the solubility and dissolution rate of SFNT using complexation method. The binary inclusion complex was prepared with β-cyclodextrin (β-CD). The molecular docking studies confirmed the hosting of SFNT into hydrophobic cavity of β-CD, while the phase solubility studies revealed the stoichiometry of complexation with a stability constant of 735.8M-1. Theternary complex was prepared by combining the SFNT-β-CD complex with PEG-6000 and HPMC polymers.The results from ATR-IR studies revealed no interaction between drug and excipients. The decreased intensities in ATR-IR peaks and changes in chemical shifts from NMR of SFNT in complexes indicate the possibility of SFNT hosting into the hydrophobic cavity of β-CD.The disappearance of SFNT peak in DSC and XRD studies revealed the amorphization upon complexation.The ternary complexes exhibited improved in vitro solubility (17.54µg/mL) compared to pure SFNT (0.19µg/mL) and binary inclusion complex (1.52µg/mL). The dissolution profile of ternary inclusion complex in 0.1 N HCl was significantly higher compared to binary inclusion complex and pure drug. In cytotoxicity studies, the ternary inclusion complex has shown remarkable effect than the binary inclusion complex and pure drug on HepG2 cell lines.

ENCAPSULATION OF EXEMESTANE WITH β-CYCLODEXTRIN AND TERNARY AGENT: FORMULATION, EVALUATION AND ANTICANCER ACTIVITY

Objective: A potent aromatase inhibitor, Exemestane, is well known for its anticancer action in breast neoplasm. The vital problem of this medicament is its poor aqueous solubility, which hinders its dissolution in body fluids. Therefore, the present study targets to enhance the water solubility of Exemestane by means of its complexation with β-cyclodextrin and a suitable ternary agent. Methods: Inclusion complexes of Exemestane with β-cyclodextrin and ternary agent were prepared by kneading and lyophilization technique. Different hydrophilic polymers and organic acids were screened for their influential ability as a co-complex with a carrier; β-cyclodextrin. The validation of complex formation was carried out by various solid-state techniques. The geometry of Exemestane in the β-cyclodextrin cavity was picturized in docking studies. The in vitro anticancer activity of prepared inclusion complex formulations carried out using MCF-7 cell lines Results: Phase solubility analysis proved HPMC E5 as the best ternary agent for complexation of Exemestane with β-cyclodextrin as it improved the stability constant of the drug from 665.92 M-1 to 1238.38 M-1. The synthesized binary and ternary inclusion complexes exhibited 2.74 and 4.62 times enhanced solubilization of Exemestane. Likewise, the dissolution characteristics of Exemestane were improved, and drug release was increased by 1.18 and 1.42 times with binary and ternary freeze-dried formulations. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) study results presented the formation of binary and ternary complexes with significantly drooped crystallinity. Docking studies predicted encapsulation of rings A, B, and C of Exemestane in the cavity of β-cyclodextrin. In-line results were obtained in Fourier transform infrared (FTIR) studies. The cell growth inhibition of 62.78 % was achieved with a ternary complex of Exemestane which was far superior than the pure active moiety that showed mere 44.56 % of inhibition. Conclusion: Altogether, it can be concluded that the inclusion complex of Exemestane boosted its aqueous solubility, resulting in its increased dissolution and in vitro anticancer activity in a breast cancer MCF-7 cell line.

Mini Review on Synthesis and Characterization Methods for Ternary Inclusion Complexes of Cyclodextrins with Drugs

Drug dependence and tolerance has become a major issue related to human health and significantly affects people living in the world today. Cyclodextrins (CDs), a family of cyclic oligosaccharides, have been widely used in the field of pharmaceutical sciences to formulate host-guest inclusion complexes with desired pharmaceutical drugs in order to improve their bioavailability and absorption by the human body. To further enhance the properties of CD-drug binary inclusion complexes, the formulation of ternary CD-drug inclusion complexes with an additive (for example polymers, organic acids, amino acids, and co-solvents) as the ternary component have been vastly explored by researchers worldwide. This review article offers a brief but comprehensive overview on various applicable synthesis and characterization methods employed by researchers for the formulation of ternary inclusion complexes of cyclodextrins with pharmaceutical drugs.

Formulation of Apigenin-Cyclodextrin-Chitosan Ternary Complex: Physicochemical Characterization, In Vitro and In Vivo Studies.

The current investigation was performed with an aim to improve the aqueous solubility, dissolution rate, and thus the biological activity of apigenin (APG) using the solubilizers hydroxypropyl beta-cyclodextrin (HPβCD) and chitosan (CTSN). A binary and ternary inclusion complexes of APG with HPβCD and CTSN were prepared by physical mixing, fusion, and solvent evaporation methods. The liquid state characterization of the APG, the solubilizers, and the physical and chemical interactions between them was done through phase solubility approach. The solid-state characterization was performed by proton nuclear magnetic resonance (1H-NMR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). The in vitro dissolution test and antioxidant activity and in vivo anti-inflammatory activity of the ternary inclusion complex in albino rats were performed to assess the performance of the APG. Phase solubility study results revealed a remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HPβCD in presence of CTSN in ternary complex with above 8 folds more increment in solubility of APG than its binary complex. The in vitro dissolution rate, antioxidant activity, and the anti-inflammatory effect of the APG ternary inclusion complex were found to be significantly higher than that of pure APG. Solid state characterization confirmed the formation of a ternary inclusion complex. 1H-NMR study gave more insight at molecular level into how different groups of APG were responsible for complex formation with the HPβCD and how CTSN was significantly influencing on the APG-HPβCD complex formed. Nevertheless, pharmacokinetic and histopathological studies of our APG-HPβCD-CTSN ternary complex would yield much rewarding results.

Ternary inclusion complex of docetaxel using ß-cyclodextrin and hydrophilic polymer: Physicochemical characterization and in-vitro anticancer activity

Ternary inclusion complex of docetaxel using ß-cyclodextrin and hydrophilic polymer: Physicochemical characterization and in-vitro anticancer activity

Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment.

The current study was designed to prepare the inclusion complex Genistein (GS) using Hydroxypropyl β cyclodextrin (HP β CD) and poloxamer 188 (PL 188). The binary inclusion complex (GS BC) and ternary inclusion complex (GS TC) were developed by microwave irradiation technique and evaluated for a comparative dissolution study. Further, the samples were assessed for FTIR, DSC, XRD, and NMR for the confirmation of complex formation. Finally, antioxidant and antimicrobial studies and cytotoxicity studies on a breast cancer (MCF-7) cell line were conducted. The dissolution study result showed a marked increment in GS dissolution/release after incorporation in binary (GS: HP β CD, 1:1) and ternary (GS: HP β CD: PL 188; 1:1:0.5) inclusion complexes. Moreover, the ternary complex exhibited a significant enhancement (p < 0.05) in dissolution than did the binary complexes. This might be due to the presence of PL 188, which helps in solubility enhancement of GS. DSC, XRD and SEM evaluation confirmed the modification in the structure of GS. FTIR and NMR results indicated the formation of an inclusion complex. The antioxidant and antimicrobial activity results revealed that GS TC has shown significant (p < 0.05) higher activity than pure GS. The cytotoxicity study results also depicted concentration-dependent cytotoxicity. GS TC exhibited significantly (p < 0.05) high cytotoxicity to cancer cells (IC50 = 225 µg/mL) than pure GS (IC50 = 480 µg/mL). Finally, it was concluded that a remarkable enhancement in the dissolution was observed after the inclusion of GS in the ternary complex and it therefore has significant potential for the treatment of breast cancer.

Supramolecular ternary inclusion complexes of Irbesartan with hydroxypropyl-beta-cyclodextrin

Current study investigated the formation of binary and ternary inclusion complexes of Irbesartan (IRB) with Hydroxypropyl-β-Cyclodextrin (HP-βCD) as host and l-Arginine (L-Arg) as ternary agent. Inclusion complexes were characterized using solubility, invitro release, DSC and XRD studies. Host-guest interactions were explored by FTIR, 1H NMR and molecular docking studies. Significant enhancement in stability constant and complexation efficiency of HP-βCD was observed in ternary complexes due to the presence of L-Arg. Ternary complexes exhibited greater solubility and dissolution of IRB than binary complexes. Thus, ternary complexation of IRB could offer an innovative strategy for improvement of solubility and dissolution of IRB.