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Related Concept Videos

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

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Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
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When a substance such as sodium chloride is added to water, it dissolves, forming an aqueous solution. The extent of dissolution is called solubility. The process of dissolution can exist in equilibrium, just like other chemical processes. Solubility equilibria are also called precipitation equilibria because the process of solubility can be reversible. The reverse of the solubility process is called precipitation.
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The formation of a solution is an example of a spontaneous process, a process that occurs under specified conditions without energy from some external source.
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There is no one solvent that can dissolve every type of solute. Some substances that readily dissolve in a certain solvent might be insoluble in a different solvent. A simple way to predict which substances dissolve in which solvent is the phrase "like dissolves like". This means that polar substances, such as salt and sugar, dissolve in a polar substance like water. In contrast, non-polar substances are more soluble in non-polar solvents such as carbon tetrachloride.
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The process of surrounding a solute with solvent is called solvation. It involves evenly distributing the solute within the solvent. The rule of thumb for determining a solvent for a given compound is that like dissolves like. A good solvent has molecular characteristics similar to those of the compound to be dissolved. For example, polar solutions dissolve polar solutes, and apolar solvents dissolve apolar solutes. A polar solvent is a solvent that has a high dielectric constant (ϵ...
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Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
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Amorphous solubility advantage: Theoretical considerations, experimental methods, and contemporary relevance.

Keisuke Ueda1, Dana E Moseson2, Lynne S Taylor3

  • 1Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

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Summary

Amorphous solubility, the drug concentration in a metastable equilibrium, offers a significant advantage for drug absorption from supersaturating formulations. Advances in theory and methods now allow accurate measurement of this key pharmaceutical parameter.

Keywords:
Amorphous solubilityColloidal drug-rich phaseLiquid–liquid phase separationSupersaturationThermodynamic activity

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Area of Science:

  • Pharmaceutical Sciences
  • Physical Chemistry
  • Drug Delivery

Background:

  • The concept of amorphous solubility advantage was first questioned 25 years ago.
  • Significant advances in theoretical understanding and experimental methods have improved the determination of amorphous solubility.
  • Amorphous solubility is now defined by phase separation into a drug-rich phase in metastable equilibrium with an aqueous phase.

Purpose of the Study:

  • To review the concept of amorphous solubility advantage.
  • To discuss theoretical considerations and experimental methods for measuring amorphous solubility.
  • To explore the contribution of supersaturation and amorphous solubility to drug absorption.

Main Methods:

  • Review of theoretical frameworks for amorphous solubility.
  • Discussion of experimental techniques for amorphous solubility determination.
  • Analysis of drug absorption from supersaturating formulations.

Main Results:

  • Amorphous solubility represents a metastable equilibrium concentration, crucial for supersaturating formulations.
  • Accurate measurement of amorphous solubility is now feasible due to theoretical and experimental advancements.
  • Understanding amorphous solubility is vital for optimizing drug absorption, particularly for poorly water-soluble drugs.

Conclusions:

  • Leveraging amorphous solubility principles can enhance the development of effective drug delivery strategies.
  • Improved understanding of amorphous solubility leads to better therapeutic outcomes for poorly water-soluble drugs.
  • Amorphous solubility is a critical parameter for absorption from supersaturating drug formulations.