Phase Solubility Diagrams Research Articles

Differentiation of puerarin chelate from salt by phase solubility test

Different from salt, metal chelate is a novel state of drug constructed by more separate coordinate bonds to form a chelating circle. Due to their composition similarity, it is hard to distinguish them except identifying ionic bond (i.e., salt) or coordinate bond (i.e., chelate) in the single crystal structure. In this study, sodium chelate (CDCC No: 1865670) and lithium salt (CDCC No: 2161617) of puerarin (PUE) was prepared. In addition to difference in single crystal structure, it was found that they showed totally different phase solubility behaviors: lithium salt demonstrated a typical inverse proportion curve as other common salts, while sodium chelate exhibited disordered scatters. However, when incorporating the unit PUE-Na complex in solution state and complexation constant K11 in chemical equation, the scatters in phase solubility diagram of chelate could be well fitted and the value of K11 was dramatically higher with orders of magnitude than the dissociation constant Kc; while processing phase solubility curve of lithium salt by incorporating complex item, it could not well match the curve at all. PUE sodium chelate is more likely to be a weak electrolyte with partial dissociation, while PUE lithium salt acted as a strong electrolyte with complete dissociation. The phase solubility test would be served as a surrogate tool for differentiation of chelates from salts when single crystal was not available.

In vitro and in silico studies of the inclusion complexation of 8-bromobaicalein with β-cyclodextrins

Baicalein, a flavone derived from Scutellaria baicalensis Georgi, exhibits potent anti-inflammatory, antiviral, and anticancer properties. Its derivative, known as 8-bromobaicalein (BB), has been found to have strong cytotoxic effect on MCF-7 human breast cancer cells. However, its limited solubility in water has hindered its potential for wider applications. To address this issue, we investigated the use of cyclodextrins specifically βCD, 2,6-di-O-methyl-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) to improve the solubility of BB through inclusion complexation. During 250 ns molecular dynamics simulations, it was found that BB can form inclusion complexes with all βCDs. These complexes exhibit two distinct orientations: chromone group insertion (C-form) and phenyl group insertion (P-form). The formation of these complexes is primarily driven by van der Waals interactions. DMβCD has the highest number of atom contacts with BB and the lowest solvent accessibility in the hydrophobic cavity. These results coincide with the highest binding affinity from the MM/GBSA-based free energy calculation method. Experimental phase solubility diagrams revealed a 1:1 stoichiometric ratio (AL type) between BB and βCDs, in which BB/DMβCD showed the highest stability. The formation of inclusion complexes was confirmed by differential scanning calorimetry and scanning electron microscope methods. Additionally, the BB/DMβCD inclusion complex demonstrated significantly higher anticancer activity against MCF-7 human breast cancer cells compared to BB alone. These findings underscore the potential of DMβCD for formulating BB in pharmaceutical and medical applications.

Prediction of the free energy of binding for cyclodextrin-steroid complexes: phase solubility and molecular dynamics studies

Steroid hormones play a crucial role in the body by acting as chemical messengers. They are, however, poorly soluble in water, and cyclodextrins can increase their solubility thus leading to increased bioavailability when used in drug formulations. Accuracy in the prediction of the free energy of binding of cyclodextrin/steroid inclusion complexes with simulation is important because of the potential value it brings by providing low-cost predictions of the real-life behavior of the cyclodextrin/steroid inclusion complex and the potential for high-through-put screening. Many computational methods exist, and it is therefore important to understand the ability of current theoretical models to accurately predict the free energy of binding for these inclusion complexes. We focused specifically on the estimation of the free energy of binding of inclusion complexes of four steroids: Hydrocortisone, dexamethasone, prednisolone, and 6α-methylprednisolone with native α-CD, β-CD, γ-CD, (2-hydroxy)propyl-β-CD, and sulfobutylether-β-CD by phase solubility as well as with α, β, and γ-CD by simulations. The simulations were assessed with both docking and the molecular mechanics combined with the generalized Born and surface area (MM/GBSA) continuum solvation approach. Considering the phase solubility diagram, (2-hydroxy)propyl-β-CD and sulfobutylether-β-CD dissolved more steroids in the higher concentration range as expected. The assessment of the free energy of binding obtained from the phase solubility and theory showed that the MM/GBSA method has shown promise in reliably generating accurate predictions in the field of calculating the free energy of binding of steroids/cyclodextrins with a correlation coefficient (R2) = 0.94.

Integrative approach for improved dofetilide solubility using β-cyclodextrin and two its substituted derivatives: Solutions and solid dispersions

The complexation an anti-arrhythmia drug dofetilide (DFT) with β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) were studied using two main approaches: phase solubility diagrams and solid dispersions technique. The phase solubility diagrams were constructed in buffer solutions with physiological values рН 2.0 и 7.4. In accordance with the protolytic properties of the drug, the solubilizing effect of cyclodextrins turned out to be more effective in a neutral environment (buffer pH 7.4): the solubility improvement of DFT in the presence of β-CD, HP-β-CD and SBE-β-CD was 3.6, 11.8 and 18.1 times, respectively. In buffer pH 2.0, the tendency for an increase in the solubilizing effect, depending on the chemical nature of the CDs used, is maintained, but the solubility of the drug almost does not grow. The binding constants for the DFT/HP-β-CD and DFT/SBE-β-CD complexes equal to 344 L·mol−1 and 429 L·mol−1 in buffer pH 7.4 indicate the formation of stable inclusion complexes and belong to the optimal range for refinement bioavailability and stability of hydrophobic drugs. Amorphous solid dispersions DFT/β-CD, DFT/HP-β-CD and DFT/SBE-β-CD with stoichiometry 1:1 were obtained by grinding method. The combination FTIR, PXRD, DSC, TGA and SEM methods confirmed the inclusion complexes formation of the drug with cyclodextrins used. Dissolution profiles of solid dispersions DFT/β-CD, DFT/HP-β-CD and DFT/SBE-β-CD were graphing in buffer solutions рН 2.0 and 7.4. Enlargement factor of DFT solubility in the composition of solid dispersions DFT/β-CD, DFT/HP-β-CD and DFT/SBE-β-CD in the neutral medium are 3.4, 4.1 and 5.2, respectively. Whereas the formation of solid inclusion complexes DFT/CDs in an acidic buffer has virtually no effect on the increase in the equilibrium concentration of the active substance in the solution. Findings have demonstrated that the use of SBE-β-CD shows the best solubilization potential for DFT both in solution and as a solid dispersion.

Micellar-type aggregates of HP-β-CD/GML inclusion complex: Increased water-solubility and effective antibacterial capabilities

The inclusion complex (IC) was successfully obtained by encapsulating glycerol monolaurate (GML) into the cavity of hydroxypropyl-β-cyclodextrin (HP-β-CD). Compared with solubility of pure GML <80 μg/mL in water, and the water-solubility of encapsulated GML was significantly improved and reached to 270,000 μg/mL. IC can form nanoparticles by self-assembly, probably assigned to its strong capability to form micellar-type aggregates. A Higuchi's AL-type phase-solubility diagram indicated the strong interaction between host and guest molecules with the formation of 1:1 GML/HP-β-CD complex and the stability constant at 6248 L/mol. Compared with pure GML, encapsulated GML at the same concentration can also show good antibacterial capabilities against S. aureus and E. coli in sterile water, and the effective preservative capabilities towards beef meatballs. The boosted enhancement in water-solubility of GML and the effective antibacterial capabilities endowed IC with potential in the application of food decontamination.

Methods of Preparation and Characterization of Cyclodextrin Encapsulated Inclusion Complex : Review

Inclusion Complex is supramolecular system which is formed by inclusion of the guest molecules into the cavity of host molecule and these molecules are held by intermolecular forces but not by covalent bond. The special characteristic of Cyclodextrins is the ability to form an inclusion complex with viable compounds. This article focuses on the various preparation methods for inclusion complexes, their formation constant, experimental and spectral approaches to demonstrate host-guest interaction. Phase solubility diagram indicated that the solubility of guest molecule increases linearly with CD concentration in AL-type and a stoichiometry of 1:1. The inclusion complex formed by various techniques was characterized by various spectroscopic methods. The study offers a variety of studies that demonstrate how cyclodextrins can be used to enhance the solubility, stability, and effectiveness of synthetic pharmaceuticals as well as their physical, chemical, and biological properties.

Characterization of behavior of the inclusion complex between Sulfobutylether-β-cyclodextrin loaded alginate/chitosan nanoparticles and indomethacin as a potential approach for drug delivery

Indomethacin (IND) is a nonsteroidal anti-inflammatory drug with low aqueous solubility and irritating gastrointestinal side effects. By complexing this drug inside the cavity of cyclodextrin (CD) and loading it into polymer nanoparticles such as Chitosan (CS) and Alginate (Alg), in addition to increasing its solubility, a targeted drug delivery platform can be created to release this drug. In this study, initially, the complex of IND with Sulfobutylether-β-cyclodextrin (SBE-β-CD) was created using the freeze-drying method. Then, by ionic gelation method, the complex was loaded into CS nanoparticles, and finally, these nanoparticles were coated with Alg to enable drug release in the intestinal environment. Complexes and nanoparticles formation were investigated by phase solubility, FTIR, HNMR, XRD, and SEM methods. Moreover, the Zeta potential method was used to measure the stability of nanoparticles coated with Alg. According to phase solubility studies, drug solubility increased linearly with increasing CD concentration, indicating an AL-type system. In addition, according to the phase solubility diagram, the stability constant and complexation efficiency were obtained 177 M−1 and 0.388, respectively. In the following, the formation of chitosan nanoparticles was confirmed through spectral shifts observed in FTIR analysis as well as morphological changes revealed in SEM analysis. Also, the zeta potential of Alg coated nanoparticles was 110.067 mV, which indicates the good stability of these nanoparticles. At the end, in vitro release studies were conducted to investigate the pH-sensitive capability of these nanoparticles at pH = 1.5 and pH = 7. The formed nanosystem successfully released 78.51 % of the drug at pH = 7 and prevented its release in acidic pH.

Solubility Enhancement of Efavirenz by Microwave Technology

In the present study, inclusion complexes of Efavirenz were developed with HPβ-cyclodextrin (HPβ-CD). The complexes were prepared by kneading method. Inclusion complexes of with HPβ-CD in aqueous solution were evaluated for phase solubility. The phase solubility diagram with the complexing agent was classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constant obtained was 820M1ˉ. The drug was compatible with the polymers used. It was confirmed by fourier-transform infrared spectra. The study indicated the presence of intermolecular hydrogen bonds between and complexing agent, resulting in the formation of amorphous form. Dissolution profiles were markedly increased in inclusion complexes, compared with the drug alone and physical mixture. Moreover, the inclusion complex prepared by kneading method was shown better aqueous solubility and dissolution profile than complex prepared by physical mixture.

Development of a consistent geochemical model of the Mg(OH)2–MgCl2–H2O system from 25°C to 120°C

The formation of magnesium chloride-hydroxide salts (magnesium hydroxychlorides) has implications for many geochemical processes and technical applications. For this reason, a thermodynamic database for evaluating the Mg(OH)2–MgCl2–H2O ternary system from 0 °C–120 °C has been developed based on extensive experimental solubility data. Internally consistent sets of standard thermodynamic parameters (ΔGf°, ΔHf°, S°, and CP) were derived for several solid phases: 3 Mg(OH)2:MgCl2:8H2O, 9 Mg(OH)2:MgCl2:4H2O, 2 Mg(OH)2:MgCl2:4H2O, 2 Mg(OH)2:MgCl2: 2H2O(s), brucite (Mg(OH)2), bischofite (MgCl2:6H2O), and MgCl2:4H2O. First, estimated values for the thermodynamic parameters were derived using a component addition method. These parameters were combined with standard thermodynamic data for Mg2+(aq) consistent with CODATA (Cox et al., 1989) to generate temperature-dependent Gibbs energies for the dissolution reactions of the solid phases. These data, in combination with values for MgOH+(aq) updated to be consistent with Mg2+-CODATA, were used to compute equilibrium constants and incorporated into a Pitzer thermodynamic database for concentrated electrolyte solutions. Phase solubility diagrams were constructed as a function of temperature and magnesium chloride concentration for comparisons with available experimental data. To improve the fits to the experimental data, reaction equilibrium constants for the Mg-bearing mineral phases, the binary Pitzer parameters for the MgOH+ — Cl− interaction, and the temperature-dependent coefficients for those Pitzer parameters were constrained by experimental phase boundaries and to match phase solubilities. These parameter adjustments resulted in an updated set of standard thermodynamic data and associated temperature-dependent functions. The resulting database has direct applications to investigations of magnesia cement formation and leaching, chemical barrier interactions related to disposition of heat-generating nuclear waste, and evaluation of magnesium-rich salt and brine stabilities at elevated temperatures.

Enhanced solubility and biological activities of Flufenamic acid through β-Cyclodextrin derivatives inclusion complexes: A comprehensive study

This study explores the formation of inclusion complexes between the solubility enhancement of Flufenamic acid (FNA) and various β-Cyclodextrins (β-CD, Hβ-CD, Mβ-CD, and Sβ-CD) using ultrasonic probe sonication method. The investigation encompasses a multi-faceted analysis, employing UV–Visible, FTIR, XRD, FE-SEM, TGA-DSC techniques and molecular docking studies. The UV–Visible spectra reveal absorption peak shifts and binding constants (Ka) indicate interaction strength, and thermodynamic parameters suggest spontaneous and favorable inclusion processes of β-CDs:FNA. Solid inclusion complexes of β-CDs:FNA were further characterized using FTIR, revealing alterations in functional groups indicative of complex formation. XRD analysis elucidates changes in crystallinity, while FE-SEM provides insights into morphological variations. Thermal stability is assessed through TGA-DSC, demonstrate the impact of inclusion on the complexes stability. Phase solubility diagrams illustrate the improved solubility of FNA in the presence of β-CDs. Mβ-CD:FNA exhibits the highest stability constant (1204 M−1), emphasizing its potential as an effective carrier. The binding energy of Mβ-CD:FNA (−46.72 kcal/mol) was lower than that of β-CD:FNA (−39.03 kcal/mol), Hβ-CD:FNA (−46.40 kcal/mol), and Sβ-CD:FNA (−46.29 kcal/mol), indicating that the hydroxypropyl group substitution enhanced the inclusion ability of β-CDs. Antibacterial activity studies against S. aureus and E. coli highlight enhanced efficacy of inclusion complexes with Mβ-CD:FNA (92.3 ± 0.18 % and 94.2 ± 0.17 %) demonstrating superior antibacterial activity. Cytotoxicity evaluations on HCT-116 cells reveal the safety profile of the β-CDs:FNA inclusion complexes, with Mβ-CD:FNA showing lower toxicity and high cell internalization compared to other formulations. The findings hold promise for applications in drug delivery, antimicrobial packaging, and the broader pharmaceutical and biotechnological fields.

Study on synthesizing the complex of sorafenib with 2-hydroxypropyl-β-cyclodextrin to enhance the anticancer activity of the drug substance

Abstract This study aims to synthesize inclusion complex derived from sorafenib (Sor) and hydroxypropyl-β-cyclodextrin (HPβCD) (denoted as [Sor-HPβCD]). The complex of Sor with HPβCD has been synthesized in a mixed solvent of H2O-DMSO, with a DMSO volume fraction of 80 %. The results of FTIR, DSC, and UV–Vis analysis have demonstrated the success of complex formation: the intensity of some characteristic peaks for the Sor binding decreased after complex formation, indicating that a part of the guest molecule has entered the cavity of the HPβCD molecule. This is further supported by the DSC analysis results, showing the transformation of the complex’s crystalline form to an amorphous form. The phase solubility diagram study also indicates that the solubility of Sor significantly increases, approximately 7 times higher than pure Sor, after complex formation. The results of the cell growth inhibition activity test in a water environment show that the complex inhibits the growth of Hep-G2 cells with an IC50 value of 62.4 μg/mL, while pure Sor does not exhibit activity as it is practically insoluble in water.

Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement.

Poor solubility and dissolution rate of drugs are largely responsible for erratic drug absorption and limited oral bioavailability. Etodolac (ETO) is a non-steroidal anti-inflammatory drug (NSAID) that is classified as BCS class II (dissolution rate-dependent absorption). ETO has high safety and efficacy in pain relief and control of inflammation. ETO is commercially available as (400- 600 mg) tablets; poor solubility and dissolution rate of ETO could result in variable oral absorption and inconsistent analgesic responses. The aim of this study was to improve solubility and dissolution rates of ETO by complexation with cyclodextrins (CDs). Four different CDs namely β-, γ-, HP β-CDs, and HP γ-CDs were prepared using three different methods; solvent evaporation (CO), freeze-drying (FD), and physical mixing (PM). The prepared drug: excipient mixtures were investigated for aqueous solubility, as well as via</i> DSC, XRD, FTIR, SEM, dissolution, and docking. The results revealed a solubility phase diagram of the AL type, indicating a 1:1 complexation of ETO: CD. These results agreed with our molecular docking calculations. DSC, FTIR, XRD, and SEM results confirmed the formation of an inclusion complex. The complexation efficiency, solubility, and dissolution enhancement were in the order of HPγ-CD > γ -CD > HPβ-CD > β-CD. FD method was superior to both CO and PM. Superior dissolution enhancements of ETO were recorded for the FD mixture (up to 90% dissolved in less than 10 min). In conclusion, γ- and hydroxypropyl γ-derivative of cyclodextrins can be considered a promising excipient for enhancement of dissolution rates concerned for ETO.

Preparation and Characterisation of Zinc Diethyldithiocarbamate-Cyclodextrin Inclusion Complexes for Potential Lung Cancer Treatment.

Zinc diethyldithiocarbamate (Zn (DDC)2), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC)2 is investigated by forming inclusion complexes with cyclodextrins. The inclusion complexes were prepared using two different types of beta-cyclodextrins, SBE-CD and HP-CD. Phase solubility diagrams for the resulting solutions were assessed; subsequently, the solutions were freeze-dried for further characterisation studies using DSC, TGA, XRD, and FTIR. The cytotoxic activity of the produced inclusion complexes was evaluated on human lung carcinoma cells using the MTT assay. The solubility of Zn (DDC)2 increased significantly upon adding beta-cyclodextrins, reaching approximately 4 mg/mL for 20% w/w CD solutions. The phase solubility diagram of Zn (DDC)2 was of the Ap-type according to the Higuchi and Connors model. Characterisation studies confirmed the inclusion of the amorphous drug in the CD-Zn (DDC)2 complexes. The cytotoxicity of Zn (DDC)2 was enhanced 10-fold by the inclusion complexes compared to the free drug. Overall, the resulting CD-Zn (DDC)2 inclusion complexes have a potential for treatment against lung cancer.

Incorporation of Loratadine-Cyclodextrin Complexes in Oral Thin Films for Rapid Drug Delivery

Rapidly dissolving polymer thin films, or oral thin films (OTFs), have recently emerged as an improved oral drug delivery vehicle with its ability to bypass liver first pass metabolism, longer shelf-life, and simpler transport and distribution requirements, compared to traditional tablets and liquid formulations. Loratadine (LOR), an antihistamine commonly used to treat allergic rhinitis, undergoes liver first pass metabolism and is a prime candidate for incorporation within an OTF. However, loratadine is a BCS II drug with low aqueous solubility. Herein, the solubility of loratadine was improved by complexation with methyl β-cyclodextrin (MBCD) by co-evaporation of 2:1, 1:1, and 1:2 LOR:MBCD ratios and incorporation into a pullulan-based OTF at 4 wt% by solvent casting at 50 °C for 30 – 35 min. A therapeutically relevant 10 mg LOR dose could be prepared in a 3 cm by 3 cm OTF. The feasibility of complexation was observed with a Bs-type phase solubility diagram, and complexation itself was confirmed via differential scanning calorimetry (DSC) by disappearance of the LOR melting peak, Fourier-transform infrared spectroscopy (FTIR) by shifting of the C=O peak, via 1H NMR spectroscopy by downfield shifting and change in peak multiplicity of the LOR aromatic protons, and via diffusion-ordered spectroscopy by a decrease in the diffusion coefficient of LOR:MBCD complex. LOR:MBCD could be incorporated homogeneously throughout an OTF, and LOR:MBCD OTFs exhibited reasonable mechanical strength and endured 12 ± 3 folds before breaking. LOR:MBCD OTFs disintegrated within 38 ± 10 s. The cumulative in vitro release of LOR:MBCD OTFs peaked at 80 % within 3–4 min of dissolution, and LOR in LOR:MBCD OTFs exhibited permeability across a 0.22 μm nitrocellulose membrane, demonstrating its applicability as a rapid drug delivery vehicle.

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.

Fundamental Properties of Ammonia Borane Aqueous Solution: Dissolution Enthalpy of Solution, Freezing Points and Solubility Curve, Thermal analysis, Stability and Phase Diagram

Fundamental Properties of Ammonia Borane Aqueous Solution: Dissolution Enthalpy of Solution, Freezing Points and Solubility Curve, Thermal analysis, Stability and Phase Diagram

Study of Component Solubility Polytherm in the System Ca(ClO3)2–[21% ClCH2CH2PO(OH)2⋅NH3 + 11% ClCH2CH2PO(OH)2⋅2NH3 + 12% NH4H2PO4 + 56% H2O]–H2O

Mutual effect of components in complex aqueous system comprising calcium chlorate, ammonium dihydrogen phosphate, and ammonium chloroethylphosphonates has been studied. Polythermal diagram of system solubility has been built in the temperature range from –40.3 to 68.0°C. Phase diagram of system solubility demarcates crystallization fields for ice, calcium chlorate hexa-, tetra-, and dihydrate, and compound of composition NH4ClO3·ClCH2CH2HPO3NH4. The compound has been isolated from supposed crystallization field and has been identified by chemical and physicochemical analysis. To provide foundation for the process of preparation of efficient stimulant and mild defoliant based on calcium chlorate and Nazhot preparation, rheological properties of components in the system Ca(ClO3)2–[21% ClCH2CH2PO(OH)2⋅NH3 + 11% ClCH2CH2PO(OH)2⋅2NH3 + 12% NH4H2PO4 + 56% H2O]–H2O have been studied. Composition–property diagram has been built for the system.

Physicochemical characterization, solubility enhancement, molecular docking, and antibacterial activity of inclusion complexes of naproxen/β-cyclodextrin derivatives: A comparative study

Naproxen (NAP) is a nonsteroidal anti-inflammatory drug. The aim of this work is to enhance the aqueous solubility and dissolution rate of naproxen (NAP) by forming an inclusion complex with β-cyclodextrin derivatives (β-CDs) such as 2-hydroxypropyl-β-cyclodextrin (Hβ-CD), methyl-β-cyclodextrin (Mβ-CD), and sulfated-β-cyclodextrin (Sβ-CD). UV–vis and fluorescence spectroscopic techniques were applied to examine the interaction of the β-CDs:NAP inclusion complexes in pH 7.4 buffer solution. The 1:1 stoichiometry of the β-CDs:NAP inclusion complexes was confirmed by the Benesi-Hildebrand method. The solid-state β-CDs:NAP inclusion complexes were obtained by co-precipitation and were characterized by FTIR, XRD, SEM, and TGA-DSC analyses. Phase solubility diagrams were calculated linearly from the slope and intercept, where the maximum apparent stability constants (Ks) were found to be 1123, 1261, and 1131 M−1 for Hβ-CD, Mβ-CD, and Sβ-CD respectively, indicating formation of the β-CDs:NAP inclusion complexes. Molecular docking was used to systematically validate formation of the β-CDs:NAP inclusion complexes. The antibacterial activity of the β-CDs:NAP inclusion complexes was described here for the first time, and it was shown that the activity of NAP against Staphylococcus aureus (91 ± 0.12%) and Escherichia coli (87 ± 0.14%) was remarkably enhanced by encapsulation in the β-cyclodextrin derivatives. The prepared solid β-CDs:NAP inclusion complexes are highly stable in aqueous media, where the antibacterial activity can be enhanced by increasing the solubility of NAP.

Design and dermatokinetic appraisal of lornoxicam-loaded ultrafine self-nanoemulsion hydrogel for the management of inflammation: In vitro and in vivo studies

The present study aimed to evaluate the impact of ultrafine nanoemulsions on the transdermal delivery of lornoxicam (LOR) for management of the inflammation. The transdermal administration of LORNE could increase the efficacy of LOR with a reduction in side effects. Merging the beneficial properties of ultrafine nanoemulsions and their components (penetration enhancers) can lead to good solubilization, a small droplet size, and more effective LOR carriers. Therefore, this study aims to develop and evaluate the potential use of ultrafine nanoemulsions of LOR (LORNE) to elucidate their skin targeting for the treatment of inflammation. Based on solubility and pseudo ternary phase diagram tests, ultrafine LORNE composed of Labrafil M 2125 CS, Cremophor RH40, and Transcutol HP to deliver LOR was developed and characterized for its physicochemical properties, emulsification, and in vitro release. The selected LORNE was incorporated into carbopol gel (LORNE-Gel) and examined for ex vivo skin permeation, retention, dermatokinetics, anti-inflammatory efficacy, and skin irritation. The selected LORNE12-Gel could improve skin permeation, retention, and dermatokinetic results significantly (p < 0.05) with enhanced CSkin max and AUC0-48h compared to LOR-Gel. Moreover, LORNE12-Gel showed a remarkable anti-inflammatory effect compared to LOR-Gel after topical application. No signs of skin irritation were observed following treatment, indicating the safety of LORNE12-Gel. Thus, this study demonstrated that LOR-loaded LORNE12-Gel could be promising as an efficient transdermal nanocarrier for an anti-inflammatory alternative.

Optimization of the stability constants of the ternary system of diclofenac/famotidine/β-cyclodextrin by nonlinear least-squares method using theoretical equations

This study aimed to establish a new method for determining the stability constants of drug/β-cyclodextrin (β-CD) complexes when multiple drugs interacting with each other coexist in the solution of complexation. The basic drug famotidine (FAM) and the acidic drug diclofenac (DIC) were used as model drugs, their solubility decreasing owing to their mutual interaction. The dissolution of both FAM and DIC was characterized by AL-type phase solubility diagrams in the presence of the other’s 1:1 complex with β-CD. When the stability constant was calculated from the slope of the phase solubility diagram using the conventional phase solubility diagram method, it was modified in the presence of the other drug. However, by performing optimization calculations that considered the interactions between the drug/β-CD complex and the drug, drug/β-CD complexes, and drugs, we were able to accurately calculate the stability constant of DIC/β-CD and FAM/β-CD complexes even in the presence of FAM and DIC, respectively. The results of the solubility profile indicated that various molecular species, which are attributed to drug-drug and drug/β-CD interactions, interfere with the values of the dissolution rate constants and saturated concentration in the solubility profiles.