Analysis of the Phase Solubility Diagram of a Phenacetin/Competitor/.BETA.-Cyclodextrin Ternary System, Involving Competitive Inclusion Complexation.

Thermodynamic studies of piroxicam in aqueous solution complexed with β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and two β-cyclodextrin derivatives, hydroxypropyl-β-cyclodextrin (HP-P-CD) and methyl-β-cyclodextrin (Me-β-CD) were performed at different temperatures and pH values using the phase solubility method. The phase solubility diagrams of β-CD, γ-CD and HP-β-CD is of AL-type behavior, indicating the formation of 1:l complexes. The related stability constants range from β-CD > γ-CD > Me-β-CD > HP-β-CD, respectively. An Ap-type solubility diagram is observed for Me-β-CD, indicating the formation of 1:2 complexes at higher CD concentrations. From the temperature dependence of the equilibrium constants the reaction enthalpies and entropies have been determined. The contributions of the reaction entropies are small and no enthalpy-entropy-compensation is observed, except for γ-CD, where a very small negative reaction entropy could be estimated. Moreover, the influence of the pH value is rather high because the differently charged forms of piroxicam show different solubility behavior in water.

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Soluble 1:1 complexes and insoluble 3:2 complexes – Understanding the phase-solubility diagram of hydrocortisone and γ-cyclodextrin

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2017.05.024 ◽

2017 ◽

Vol 531 (2) ◽

pp. 504-511 ◽

Cited By ~ 12

Author(s):

Christian Schönbeck ◽

Tobias L. Madsen ◽

Günther H. Peters ◽

René Holm ◽

Thorsteinn Loftsson

Keyword(s):

Solubility Diagram ◽

Phase Solubility ◽

Phase Solubility Diagram

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Elucidation of the complexation mechanism between (+)-usnic acid and cyclodextrins studied by isothermal titration calorimetry and phase-solubility diagram experiments

Journal of Molecular Recognition ◽

10.1002/jmr.936 ◽

2009 ◽

Vol 22 (3) ◽

pp. 232-241 ◽

Cited By ~ 30

Author(s):

Freimar Segura-Sanchez ◽

Kawthar Bouchemal ◽

Geneviève Lebas ◽

Christine Vauthier ◽

Néréide S. Santos-Magalhaes ◽

...

Keyword(s):

Isothermal Titration Calorimetry ◽

Usnic Acid ◽

Solubility Diagram ◽

Titration Calorimetry ◽

Phase Solubility ◽

Complexation Mechanism ◽

Phase Solubility Diagram

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Molecular solubilization of fullerene C60 in water by γ-cyclodextrin thioethers

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.8.188 ◽

2012 ◽

Vol 8 ◽

pp. 1644-1651 ◽

Cited By ~ 19

Author(s):

Hai Ming Wang ◽

Gerhard Wenz

Keyword(s):

Light Scattering ◽

Dynamic Light Scattering ◽

Equilibrium State ◽

Solubility Diagram ◽

Fullerene C60 ◽

Phase Solubility ◽

Particle Sizes ◽

Organic Cosolvents ◽

Phase Solubility Diagram

Various hydrophilic γ-cyclodextrin (CD) thioethers, containing neutral or ionic side arms were found to form molecular disperse solutions of C60 in water reaching concentrations of 15 mg/L. Equilibrium state was approached after seven days without the use of organic cosolvents. The 1:2 stoichiometry of the C60/γ-CD thioether complexes was demonstrated by a parabolic phase-solubility diagram. In contrast, native γ-CD forms nanoparticles with C60. Particle sizes of C60 were determined by dynamic light scattering.

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The Influence of Cyclodextrin and pH on the Solubility of Ketoprofen

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.506.433 ◽

2012 ◽

Vol 506 ◽

pp. 433-436 ◽

Cited By ~ 1

Author(s):

W. Samprasit ◽

Theerasak Rojanarata ◽

Prasert Akkaramongkolporn ◽

Tanasait Ngawhirunpat ◽

Praneet Opanasopit

Keyword(s):

Aqueous Solution ◽

Stability Constant ◽

Zeta Potential ◽

Solubility Diagram ◽

Phase Solubility ◽

Combined Approach ◽

Cyclodextrin Complexation ◽

Cyclodextrin Cavity ◽

Phase Solubility Diagram ◽

Apparent Stability

Cyclodextrin complexation and pH adjustments have been reported as useful tools to increase the solubility of drug. The aim of this study was to investigate the influence of both cyclodextrin and pH on the overall solubility of ketoprofen. β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) were used for the preparation of inclusion complex by shaking method in aqueous solution at pH 2, 5, 7 and 10. It was found that the solubility of ketoprofen significantly increased with increasing pH and cyclodextrin concentration, showing AL type phase solubility diagram. However, the apparent stability constant of complex (KC) was found to decrease with increasing pH due to the decreased affinity of ionized drug to cyclodextrin cavity. The ionization of ketoprofen increased when the pH was raised, corresponding with its higher zeta potential. The result indicated that the solubility of ketoprofen could be improved by using a combined approach of pH adjustments and complexation with cyclodextrin. Moreover, the unionized drug that was formed by pH adjustments interacted with cyclodextrin more strongly than the ionized drug.

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INTESTINAL ABSORPTION OF EPROSARTAN MESYLATE FROM SELF EMULSIFYING SYSTEM AND CYCLODEXTRIN COMPLEX

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i2.16215 ◽

2017 ◽

Vol 9 (2) ◽

pp. 302

Author(s):

Mohammed M. Abdol Quader ◽

Mohamed A. Osman ◽

Gamal M. El Maghraby

Keyword(s):

Inclusion Complex ◽

Intestinal Absorption ◽

Inclusion Complexation ◽

Solubility Diagram ◽

Phase Solubility ◽

Font Size ◽

Transport Parameters ◽

Cyclodextrin Complex ◽

Scanning Calorimetry ◽

Intestinal Membrane

Objective: The aim of this work was to determine the intestinal membrane transport parameters of eprosartan mesylate (EM) and to investigate self-nano emulsifying drug delivery systems (SNEDDS) and inclusion complexation with hydroxypropyl b cyclodextrin (HPbCD) for enhanced intestinal absorption of eprosartan mesylate. Methods: The intestinal absorption was monitored using the in situ rabbit intestinal perfusion technique. SNEDDS was developed using labrafil, Lauroglycol with a tween in the presence of ethanol. Inclusion complexation was achieved by construction of phase solubility diagram in the presence of HPbCD. The prepared complex was evaluated using Fourier Transform Infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The drug was found to be poorly absorbed from the jejuno-ileum and the colon with the absorption being mainly through paracellular pathway. An inclusion complex was developed between the drug and HPβCD. Perfusion of the drug in the nanoemulsion formulation or as an inclusion complex resulted in a significant increase in the intestinal absorption of the drug compared with the control.Conclusion: SNEDDS and inclusion complexation are promising strategies for enhanced intestinal absorption of eprosartan mesylate.

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Oral Bioavailability Enhancement of Amisulpride: Complexation and its Pharmacokinetics and Pharmacodynamics Evaluations

Drug Metabolism Letters ◽

10.2174/1872312813666191018152226 ◽

2020 ◽

Vol 13 (2) ◽

pp. 132-144

Author(s):

Prajapati Jagruti B. ◽

Sawant Krutika K. ◽

Bhramanand Dubey

Keyword(s):

Complex Formation ◽

Inclusion Complex ◽

Oral Bioavailability ◽

Water Solubility ◽

Solubility Diagram ◽

Phase Solubility ◽

Linear Type ◽

Market Product ◽

Pure Drug ◽

Phase Solubility Diagram

Background: Many CNS drugs have low bioavailability due to their poor water solubility of extensive first-pass metabolism and hence have less effectiveness. Objective: The present study aims to enhance the solubility and oral bioavailability of poorly watersoluble antipsychotic drug Amisulpride (AMS) through complexation with 2-hydroxypropyl β- cyclodextrin (HPβCD). It has slow and erratic absorption after oral administration. Methods: This report describes the study of the phase solubility diagram, preparation of the inclusion complex and tablet of prepared inclusion complex, characterization of the physico-chemical properties of the inclusion complex and tablet. Results: In-vitro study (100 % drug release in 15 minutes), and in-vivo study of an AL-type (linear type) phase solubility diagram indicated a complex of AMS-HP-β-CD with the constant complex formation of 13245 M−1 at 37°C. The complex formation was confirmed by DSC, IR, and X-ray diffraction. The extent of absorption of the complex was determined in rats and was compared with that of pure drug and the market product. The peak plasma concentration of pure drug was 30.05 ± 1.3 ng/ml (Cmax) at 60 ± 3 min, whereas with the market product the value was 54.85 ± 1.2 ng/ml at 40 ± 1 min and with AMS-HPβCD inclusion complex the value was 79.01 ± 1.5 ng/ml. The AUCtot of the pure drug was 2980.34±3.6, the market product was 7238.73±2.9 and of the inclusion complex was 11871.1±2.8. Conclusion: Pharmacodynamic studies in mice showed improved effectiveness of drug compared to pure drug. The oral bioavailability of AMS was improved from 48% to 78%.

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Preparation and in vitro Evaluation of Inclusion Complexes of Nelfinavir with Chemically Modified ?-cyclodextrins

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v11i2.14558 ◽

2013 ◽

Vol 11 (2) ◽

pp. 107-116 ◽

Cited By ~ 3

Author(s):

Shivanand Hiremath ◽

Ganesh Godge

Keyword(s):

Inclusion Complex ◽

Inclusion Complexes ◽

Solubility Diagram ◽

Aqueous Solubility ◽

Water Soluble ◽

Phase Solubility ◽

Ir Study ◽

Order Complexes ◽

Phase Solubility Diagram

Nelfinavir is a poorly water-soluble antiretroviral drug with relatively low bioavailability. In the present study, the practically insoluble drug, nelfinavir (NFV) and its inclusion complexes with hydroxypropyl-?-cyclodextrin (HP-?-CD) were investigated to improve the aqueous solubility and the dissolution rate of the drug, thus enhancing its bioavailability. The phase solubility diagram with HP-?-CD was classified as AL-type at all temperatures investigated, indicating the formation of higher order complexes. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 145.49, 188.45 and 255.54 M-1 at 25, 37 and 45 ± 0.5°C, respectively. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased; this could be mainly attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP- ? -CD. Absence of endothermic and characteristic diffraction peaks corresponding to NFV was observed for the inclusion complex in DSC and PXRD. FT-IR study indicated that the presence of intermolecular hydrogen bonds between NFV and HP-?-CD in inclusion complex, resulting in the formation of amorphous form. DOI: http://dx.doi.org/10.3329/dujps.v11i2.14558 Dhaka Univ. J. Pharm. Sci. 11(2): 107-116, 2012 (December)

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