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Phase Diagrams of Ternary Systems01:28

Phase Diagrams of Ternary Systems

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Consider a ternary system, which is composed of three components: water (W), ethanoic acid (E), and trichloromethane (T). Here, Ethanoic acid (E) is fully miscible with both water (W) and trichloromethane (T), meaning it can mix entirely with either of them. However, water and trichloromethane have partial miscibility, meaning they can only mix to a certain extent, beyond which two separate phases will form.The phase diagram of a ternary system is represented as an equilateral triangle, where...
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Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
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Stability of Substituted Cyclohexanes02:30

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This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.
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Antifungal Agents01:15

Antifungal Agents

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Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
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Structure of Carboxylic Acid Derivatives
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Depending upon the different spatial orientation of the substituents, the disubstituted cycloalkanes exhibit two types of stereoisomers. The cis isomers have the substituents on the same side of the ring, whereas the trans isomers have the substituents on the opposite sides. These stereoisomers exhibit different physical properties and cannot be interconverted without breaking the carbon-carbon bonds.
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Comparative analysis of binary and ternary cyclodextrin complexes with econazole nitrate in solution and in solid

Mario Jug1, Natascia Mennini2, Katalin E Kövér3

  • 1Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, Zagreb 10000 HR, Croatia.

Journal of Pharmaceutical and Biomedical Analysis
|January 22, 2014
PubMed
Summary

This study explored econazole nitrate (ECN) complexation with cyclodextrin (CD) derivatives. Ternary complexes with sulfobutyl-βCD (SBEβCD) and citric acid (CA) significantly enhanced ECN dissolution for improved oral candidosis therapy.

Keywords:
(1)H NMRCo-grindingCyclodextrinsEconazole nitrateSolidstate analysis

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Delivery Systems
  • Physical Chemistry

Background:

  • Econazole nitrate (ECN) is a poorly water-soluble antifungal agent.
  • Improving ECN solubility and dissolution is crucial for effective oral candidosis treatment.
  • Cyclodextrins (CDs) are widely used to enhance the solubility of poorly soluble drugs.

Purpose of the Study:

  • To investigate the complexation of ECN with various β-cyclodextrin (βCD) derivatives.
  • To evaluate the synergistic effect of third compounds, such as citric acid (CA), on ECN solubility.
  • To develop an optimized ECN delivery system for enhanced oral cavity drug delivery.

Main Methods:

  • Phase-solubility studies to determine drug-CD interactions and complex stoichiometry.
  • 1D and 2D (1)H NMR spectroscopy to confirm inclusion complex formation and elucidate inclusion modes.
  • Preparation of binary and ternary systems using co-grinding techniques.
  • Characterization of solid systems using DSC, X-ray powder diffractometry, and in vitro dissolution studies.

Main Results:

  • Sulfobutyl-βCD (SBEβCD) and hydroxypropyl-βCD (HPβCD) showed good complexation with ECN.
  • Ternary systems with SBEβCD and CA exhibited a significant synergistic effect, forming highly soluble complexes.
  • Co-grinding of ECN/SBEβCD/CA resulted in a 66.62-fold increase in ECN dissolution efficiency, outperforming binary systems.

Conclusions:

  • SBEβCD is the most effective CD for ECN complexation and solubilization.
  • The ternary system of ECN/SBEβCD/CA demonstrates superior dissolution properties.
  • This ternary system holds significant potential for developing an advanced ECN delivery system for oral candidosis treatment.