Efficiency Complexity Research Articles

QbD Assisted Systematic Review for Optimizing the Selection of PVP as a Ternary Substance in Enhancing the Complexation Efficiency of Cyclodextrins: a Pilot Study.

Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study.

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

Characterization, Preparation, and Promotion of Plant Growth of 1,3-Diphenylurea/β-Cyclodextrin Derivatives Inclusion Complexes.

The study aimed to prepare inclusion complexes of 1,3-diphenylurea (DPU) with β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HP-βCD) using a three-dimensional ground mixture (3DGM). Their physicochemical properties, intermolecular interactions, solubilities, and plant growth-promoting activities were investigated on broccoli sprouts. Phase-solubility diagrams indicated the stability constant (Ks) and complexation efficiency (CE) of βCD/DPU were found to be K1/1 = 250 M-1, CE = 2.48× 10-3. The Ks and CEs of HP-βCD/DPU were found to be K1/1 = 427 M-1, CE = 3.93 × 10-3 and K2/1 = 196 M-1, CE = 1.93 × 10-3 respectively. The powder X-ray diffraction results of 3DGM (βCD/DPU = 2/1, HP-βCD/DPU = 2/1) showed that the diffraction peaks originating from the DPU and βCD disappeared, indicating a halo pattern. Differential scanning calorimetry results showed an endothermic peak at 244 °C derived from the melting point of DPU, but the endothermic peak disappeared in the 3DGM (βCD/DPU = 2/1, HP-βCD/DPU = 2/1). Near-infrared absorption spectra showed peak shifts in 3DGM (βCD/DPU and HP-βCD/DPU) at the -CH and -NH groups of DPU and the -OH groups of βCDs and free water. In the dissolution test (after 5 min), the concentration of intact DPU was 0.083 μg/mL. However, the dissolution concentrations of DPU in the 3DGM (βCD/DPU = 1/1), 3DGM (βCD/DPU = 2/1), 3DGM (HP-βCD/DPU = 1/1), and 3DGM (HP-βCD/DPU = 2/1) were 3.27, 3.64, 5.70, and 7.03 μg/mL, respectively, indicating higher solubility than that of the intact DPU. Further, 1H-1H NOESY NMR spectroscopic measurements showed cross-peaks between H-A (7.32 ppm) and H-B (7.12 ppm) of DPU and H-6 (3.79 ppm) in the βCD cavity of the 3DGM (βCD/DPU = 2/1). A cross-peak was also observed among DPU H-A (7.32 ppm), H-B (7.11 ppm), and H-6 (3.78 ppm) in the βCD cavity. The results of the broccoli sprout cultivation experiment showed that 3DGM (βCD/DPU = 1/1), 3DGM (βCD/DPU = 2/1), 3DGM (HP-βCD/DPU = 1/1), and 3DGM (HP-βCD/DPU = 2/1) increased the stem thickness compared with that of the control group (DPU). These results indicated that the βCD/DPU and HP-βCD/DPU inclusion complexes were formed by the three-dimensional mixing and milling method, which enhanced the solubility and plant growth-promoting effects.

Formulation of Silymarin-β Cyclodextrin-TPGS Inclusion Complex: Physicochemical Characterization, Molecular Docking, and Cell Viability Assessment against Breast Cancer Cell Lines.

Silymarin (SIL) is a poorly water-soluble flavonoid reported for different pharmacological properties. Its therapeutic applications are limited due to poor water solubility. In this study, the solubility of silymarin has been enhanced by preparing freeze-dried binary and ternary complexes using beta cyclodextrin (βCD) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS). The stoichiometry of the drug and the carrier was selected from the phase solubility study. The dissolution study was performed to assess the effect of complexation on the release pattern of SIL. The formation of inclusion complexes was confirmed by different physicochemical studies. Finally, a cell viability assay (MCF 7; breast cancer cell line) was performed to compare the activity with free SIL. The phase solubilization results revealed the formation of a stable complex (binary) with a stability constant and complexation efficiency (CE) value of 288 mol L-1 and 0.045%. The ternary sample depicted a significantly enhanced stability constant and CE value (890 mol L-1 and 0.14%). The release study results showed a marked increase in the release pattern after addition of βCD (alone) in the binary mixture (49.4 ± 3.1%) as well as inclusion complex (66.2 ± 3.2%) compared to free SIL (32.7 ± 1.85%). Furthermore, with the addition of TPGS in SIL-βCD (ternary), the SIL release was found to be significantly enhanced from the SIL ternary mixture (79.2 ± 2.13%) in 120 min. However, fast SIL release was achieved with 99.2 ± 1.7% in 45 min for the SIL ternary complex. IR and NMR spectral analysis results revealed the formation of a stable complex with no drug-polymer interaction. The formation of complexes was also confirmed by the molecular docking study (docking scores of 4.1 and -6.4 kcal/mol). The in vitro cell viability result showed a concentration-dependent activity. The IC50 value of the SIL ternary complex was found to be significantly lower than that of free SIL. The findings of the study concluded that the prepared SIL inclusion complex can be used as an alternative oral delivery system to enhance solubility, dissolution, and biological activity against the tested cancer cell line.

β-cyclodextrin-based nanosponges for crocetin delivery: Physicochemical characterization, aqueous solubility, and bioactivity

Crocetin (CRT) is a natural carotenoid compound with promising health benefits but its use is restricted because of the poor aqueous solubility. Therefore, cyclodextrin-based nanosponges (CDNSs), a kind of water-soluble supramolecular macrocyclic polymer, was employed to load CRT for improving the solubility. The β-CDNSs with different molar ratio of β-CD and crosslinker were synthesized and β-CDNS 1:8 was chosen. The loading capacity (LC) and complexation efficiency (CE) of prepared CRT-loaded β-CDNS were about 17.92% and 94.64%. The formation of inclusion and non-inclusion structure of CRT-loaded β-CDNS was confirmed by different techniques. The surface properties and dispersibility were also studied. Besides, the water solubility of CRT was significantly increased to 7.27 μg/mL. The antioxidant activity of CRT was enhanced. The in vitro cytotoxicity of CRT for normal cells was reduced and for tumor cells was increased through the loading of β-CDNS. In summary, this work demonstrated β-CDNS could be used for the delivery of CRT and promote the application of CRT in many fields.

Development of Fenofibrate/Randomly Methylated β-Cyclodextrin-Loaded Eudragit® RL 100 Nanoparticles for Ocular Delivery.

Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-β-CD (RMβCD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RMβCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMβCD complex. FE-loaded Eudragit® nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen’s egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RMβCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.

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.

Effect of Soluplus® on γ-cyclodextrin solubilization of irbesartan and candesartan and their nanoaggregates formation

The poor aqueous solubility of irbesartan (IRB) and candesartan cilexetil (CAC) may hamper their bioavailability when orally or topically administered. Among several attempts, the promising nanoaggregate formation by γ-cyclodextrin (γCD) complexation of drugs in aqueous solution with or without water-soluble polymers was investigated. According to phase solubility studies, Soluplus® showed the highest complexation efficiency (CE) of drug/γCD complexes among the polymers tested. The aqueous solubility of IRB and CAC was markedly increased as a function of Soluplus® concentrations. The binary drug/γCD and ternary drug/γCD/Soluplus® complex formations were supported and confirmed by solid-state characterizations, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FT-IR) spectroscopy. The true inclusion mode was also proved by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The nanoaggregate size and morphology of binary and ternary systems were observed using dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques. The size of these nanocarriers depends on the concentration of Soluplus®. The use of Soluplus® could significantly enhance drug solubility and stabilize complex nanoaggregates, which could be a prospective platform for drug delivery systems.

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

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

Inclusion complexes of cannabidiol with β-cyclodextrin and its derivative: Physicochemical properties, water solubility, and antioxidant activity

Cannabidiol (CBD), which has a wide variety of biological activities, is one of the phytocannabinoids from Cannabis sativa L. However, due to the poor aqueous solubility, its applications in food, cosmetic, and pharmaceutical fields are limited. Moreover, the previous researches on the improvement in the solubility of CBD are rare. Cyclodextrins (CDs) are useful materials to improve the solubility of poorly water-soluble molecules. Therefore, this work was aimed to study the physicochemical properties, water solubility, and dissolution rate of the inclusion complexes of CBD with β-cyclodextrin (β-CD) and 2, 6-di-O-methyl-β-cyclodextrin (DM-β-CD), and to determine the influence of complexation on the antioxidant activity of CBD. Job’s plot and phase solubility study revealed that CBD formed inclusion complexes with β-CD and DM-β-CD at a 1:1 stoichiometric ratio. The thermodynamics analysis demonstrated that the inclusion process was spontaneous and endothermic. Then, the inclusion complexes of CBD with β-CD or DM-β-CD were prepared and characterized by PXRD, FT-IR, DSC, SEM, and 1H NMR. The loading efficiency (LE) of the two inclusion complexes was 20.4% and 17.7% respectively, while the complexation efficiency (CE) was 92.4% and 90.8% respectively. Moreover, the results of molecular docking further showed that CBD was encapsulated successfully. The results also displayed that the water solubility of CBD in CBD/β-CD inclusion complex (IC) and CBD/DM-β-CD IC was significantly increased to 0.395 and 14.118 μg/mL, which was enhanced by 17-fold and 614-fold respectively at such a high LE, and the in vitro dissolution rate of CBD was also promoted after complexation. Besides, the antioxidant activity of CBD was improved after encapsulation with β-CD and DM-β-CD. Significantly, the ABTS free radical scavenging ability of the two inclusion complexes was better than that of Vitamin C (Vc).

Synthesis and evaluation of B-cyclodextrin Based Nanosponges of 5- Fluorouracil by Using Ultrasound Assisted Method

&#x0D; CD-nanosponges were prepared by crosslinking B-CD with diphenylcarbonate (DPC) using ultrasound assisted technique. 5-FU was incorporated with NS by freeze drying, and the phase solubility study, complexation efficiency (CE) entrapment efficiency were performed. Also, the particle morphology was studied using SEM and AFM. The in-vitro release of 5-FU from the prepared nanosponges was carried out in 0.1N HCl.&#x0D; 5-FU nanosponges particle size was in the nano size. The optimum formula showed a particle size of (405.46±30) nm, with a polydispersity index (PDI) (0.328±0.002) and a negative zeta potential (-18.75±1.8). Also the drug entrapment efficiency varied with the CD: DPC molar ratio from 15.6 % to 30%. The SEM and AFM showed crystalline and porous nature of the nanosponges. The in vitro drug release study of the selected formula 5-FUNS2 exhibited the fastest dissolution rate which is 56% in the first hr.&#x0D; Different molar ratios of (cyclodextrin to crosslinker) (CD: DPC) has a proficient effect on complexation efficiency (CE), apparent stability constant (Kst) and entrapment efficiency of 5-FU. 5-FUNS2 with (1:4) molar ratio showed the best result of CE, Kst and entrapment efficiency. 5-FUNS2 gave a higher release rate than the 5-FU-BCD inclusion complex and 5-FU solution. Surface morphology of the prepared nanosponges by SEM, AFM indicate that nanosized and highly porous nanosponges was obtained. The overall results suggest that cyclodextrin nanosponges could be a promising 5-FU delivery system utilizing the suitable formula.

Formulation of Piperine Ternary Inclusion Complex Using β CD and HPMC: Physicochemical Characterization, Molecular Docking, and Antimicrobial Testing

The present study was designed to evaluate the effect of hydroxyl propyl methyl cellulose (HPMC) on the complexation efficiency and dissolution of piperine (PPR) and β cyclodextrin (β CD) complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and microwave irradiation methods. The samples were further evaluated for physicochemical evaluation, morphology, antimicrobial, and antioxidant activities. The binary and ternary samples showed high stability constant (Ks) value and complexation efficiency (CE). The dissolution study results revealed marked enhancement in the release of the binary inclusion complex and ternary inclusion complex compared to pure PPR. Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and molecular docking results confirm the complex formation. X-ray powder diffractometry (XRD) and scanning electron microscopy (SEM) data revealed modification in the structure of PPR. 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and antimicrobial results showed enhanced activity in the PPR complex in comparison to pure PPR. In conclusion, a remarkable enhancement in dissolution, antioxidant and antimicrobial activities were attained due to marked improvement in solubility through complexation of PPR with HPMC/β CD.

The investigation of binary and ternary sulfobutylether-β-cyclodextrin inclusion complexes with asiaticoside in solution and in solid state

Asiaticoside (AS) is poorly water-soluble compound that can lead to low the bioavailability. The aims of this study were to determine the cyclodextrin (CD) solubilization of AS and characterize binary AS/CD and ternary AS/CD/polymer complexes in solution- and solid-state. Thermal stability of AS through heating process was determined and found that It could withstand by heating through sonication method. Phase-solubility profiles showed that β-cyclodextrin (βCD) exhibited the greatest solubilizing effect but sulfobutylether-βCD (SBEβCD) was selected for further investigations due to its relatively high complexation efficiency (CE) value. The effect of polymers that were poloxamer 407 (P407) and chitosan (CS) on CD solubilization were investigated. It was found that the increment of CE was resulted from the formation of ternary complexes or complex aggregates with confirmed by dynamic light scattering and transmission electron microscopy. Proton nuclear magnetic resonance (1H NMR) data indicated that the cyclohexane moiety of AS was totally inserted into the hydrophobic inner cavity of SBEβCD in the presence or absence of polymer. The molecular modeling study displayed the binding orientation of such complex which correlated to 1H NMR result. The solid state characterized by Fourier transform infra-red, differential scanning calorimetry and powder X-ray diffraction demonstrated the formation of binary AS/SBEβCD and ternary AS/SBEβCD/polymer inclusion complexes. The enhancement of AS dissolution was achieved in both binary and ternary complexes. The permeation study showed that ternary AS/SBEβCD/CS nanoparticles exhibited a promising controlled drug release nanocarrier.

Formulation of Curcumin-β-cyclodextrin-polyvinylpyrrolidone supramolecular inclusion complex: experimental, molecular docking, and preclinical anti-inflammatory assessment

This research planned to ameliorate an aqueous solubility and dissolution of Curcumin (CUR) by the formulation of inclusion complex with β-cyclodextrin (β-CD) and polyvinylpyrrolidone (PVP). The phase solubility study was performed to assess the solubility of CUR. The prepared CUR complex assessed for dissolution study, physicochemical evaluation, in-vitro antioxidant activity, molecular modeling, and anti-inflammatory assessment. The pivotal findings of phase-solubility studies demonstrate apparent stability constant (Kc) and complexation efficiency (CE) values for CUR-β-CD and CUR-β-CD-PVP complex was 175.4 M −1, 1.15% and 833.3.2 M −1 and 5.21%, respectively. The characterization results revealed amorphization of crystalline state (CUR) into amorphous state. The maximum drug release found with the ternary CUR complex (F7), i.e. 45.41 ± 3.78% in 6 h study. The chemical shift in the NMR supports that the aromatic ring of CUR is completely complexed inside the β-CD cavity. The antioxidant activity of pure CUR was found to be 58.02 ± 2.21% and CUR ternary complex (F7) showed significantly higher activity to 96.02 ± 2.46%. The in-vivo effect of CUR complex (F7) was also found significantly higher than that of pure CUR. The molecular modeling study depicted that PVP increased the stability of the ternary complex by forming the link between CUR and β-CD. Thus, the ternary inclusion complex of CUR-β-CD-PVP could contribute as an innovative outcome in the enhancement of solubility and in-vivo activity.

Efficiency in Projects of Creative Industries

The projects’ development in dynamically developing creative industries requires a search for new sources of creating the competitive advantage. One of the approaches – in addition to the risk analysis – is the efficiency management. The aim of the study is to evaluate the complexity of the efficiency management in business (especially innovative) projects. In the article, there is presented the methodology of WZZE (complexity of efficiency management) index construction, referring to the 11 specific factors.

Influence of Water-soluble polymers on Epalrestat ternary complexation by kneading

The study reported in this current work objected to demonstrate the formation of binary and ternary inclusion complexes of Epalrestat (EP), a poorly water-soluble acidic type drug, with s-cyclodextrin (CD) and with water-soluble polymers PVP K30 and HPMC E4. The solid systems of EP with s-CD and water-soluble polymers were obtained by kneading and characterized for phase solubility, saturation solubility, dissolution, stability studies. FTIR, DSC, PXRD and SEM data indicated the positive influence of s-CD and hydrophilic polymers on EP solubility and dissolution. Phase solubility studies were carried out to evaluate the solubilizing power of CD, with regards to EP in combination with water-soluble polymers, and to determine the apparent stability constants (Ks) and complexation efficiency (CE) of the complexes. Phase solubility studies showed AL (linear) type of solubility curve for the ternary complexes it also showed amelioration in Ks value for ternary complexes. The CE of s-CD towards EP was promoted by water-soluble polymers signifying its use as a ternary component. The dissolution rate of EP and solubility were undoubtedly improved by complexation with s-CD as compared to model drug EP alone. Ternary complexes incorporated with PVP K 30 and HPMC E4 proved better than binary complex. Hence, the water-soluble carrier could be exploited as a ternary component to improve the solubility of EP via s-CD complexation.

Effect of cyclodextrin and cosolvent on the solubility and antioxidant activity of caffeic acid.

Caffeic acid is a natural phenylpropanoid that exhibits various health benefits. However, it suffers from a poor aqueous solubility limiting its application. This drawback could be overcome by complexation in cyclodextrins (CD) or cosolvency. Herein, we investigated, for the first time, the combined effect of CD and ethanol as cosolvent on complexation, solubilization and antioxidant activity of caffeic acid. Results showed that CD, ethanol and their combined use enhanced the solubility of this phenylpropanoid. However, the presence of ethanol affects the formation of inclusion complexes as lower formation constants (Kf) and complexation efficiencies (CE) were obtained while increasing the ethanol percentage (0-45% v/v). No inclusion complex could be observed at 45% v/v ethanol. These results were confirmed by 2D DOSY and 2D ROESY NMR experiments. Furthermore, the antioxidant activity of caffeic acid in the combined system was enhanced consequent to its increased solubility.

Cyclodextrins as Drug Carriers in Pharmaceutical Technology: The State of the Art.

Cyclodextrins (CDs) are versatile excipients with an essential role in drug delivery, as they can form non-covalently bonded inclusion complexes (host-guest complexes) with several drugs either in solution or in the solid state. The main purpose of this publication was to carry out a state of the art of CDs as complexing agents in drug carrier systems. In this way, the history, properties and pharmaceutical applications of the CDs were highlighted with typical examples. The methods to enhance the Complexation Efficiency (CE) and the CDs applications in solid dosage forms were emphasized in more detail. The main advantages of using these cyclic oligosaccharides are as follows: (1) to enhance solubility/ dissolution/ bioavailability of poorly soluble drugs; (2) to enhance drug stability; (3) to modify the drug release site and/or time profile; and (4) to reduce drug side effects (for example, gastric or ocular irritation). These compounds present favorable toxicological profile for human use and therefore there are various medicines containing CDs approved by regulatory authorities worldwide. On the other hand, the major drawback of CDs is the increase in formulation bulk, once the CE is, in general, very low. This aspect is particularly relevant in solid dosage forms and limits the use of CDs to potent drugs. CDs have great potential as drug carriers in Pharmaceutical Technology and can be used by the formulator in order to improve the drug properties such as solubility, bioavailability and stability. Additionally, recent studies have shown that these compounds can be applied as active pharmaceutical ingredients.

Host-guest interaction study of Efavirenz with hydroxypropyl‑β‑cyclodextrin and l‑arginine by computational simulation studies: Preparation and characterization of supramolecular complexes

The present study demonstrates the solubility and dissolution enhancement of Efavirenz (EFV) through preparation of supramolecular inclusion complexes. The supramolecular system comprising of EFV, hydroxypropyl‑β‑cyclodextrin (HP-β-CD) and l‑Arginine was prepared by physical mixing and spray drying methods. The complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, 1H NMR spectroscopy and FT-IR spectroscopy to study alteration in crystallinity of drug. Intrinsic stability constant values (Kc) and complexation efficiency (CE) of HP-β-CD was substantially enhanced due to addition of l‑Arginine. Improved solubility and dissolution was evidenced in the supramolecular system than binary system of EFV and HP-β-CD. Computational modelling and molecular dynamics study revealed that l‑Arginine increased the stability of the complex by bridging between the EFV and the HP-β-CD. It also confirmed that l‑Arginine was positioned on the outer surface of complex and improved polar surface of inclusion complex resulting in increased solubility of the complex. Thus, supramolecular inclusion complexes of EFV with HP-β-CD and l‑Arginine could contribute as an innovative outcome in formulation development of EFV through solubility and dissolution enhancement.

Study on effect of L-arginine on solubility and dissolution of Zaltoprofen: Preparation and characterization of binary and ternary cyclodextrin inclusion complexes

The present study demonstrated the binary and ternary complexes of Zaltoprofen (ZPF) with β-CD and HP-β-CD. The products were characterized using solubility, in vitro dissolution, and DSC studies. The mode of interaction of guest and host was revealed through 1H NMR and FT-IR studies. A significant increase was noticed in the stability constant (Kc) and complexation efficiency (CE) of β-CD and HP-β-CD due to addition of L-Arg in ternary complexes. The ternary complexes showed greater increase in solubility and dissolution of ZPF than binary complexes. Thus, ternary system of ZPF could be an innovative approach for its solubility and dissolution enhancement.