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Related Concept Videos

Common Ion Effect03:24

Common Ion Effect

47.9K
Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Châtelier’s principle. Consider the dissolution of silver iodide:
47.9K
Factors Affecting Solubility04:01

Factors Affecting Solubility

38.0K
Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Chȃtelier’s principle. Consider the dissolution of silver iodide:
38.0K
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

821
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).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
821
Basicity of Heterocyclic Aromatic Amines01:25

Basicity of Heterocyclic Aromatic Amines

7.1K
Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
7.1K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

4.0K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
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Precipitation of Ions03:11

Precipitation of Ions

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Predicting Precipitation
The equation that describes the equilibrium between solid calcium carbonate and its solvated ions is:
30.8K

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Imipramine solubility-pH profiles: self-aggregation vs. common-ion effect.

Olivera S Marković1, Miloš P Pešić2, Alex Avdeef3

  • 1University of Belgrade - Institute of Chemistry, Technology and Metallurgy - National Institute of the Republic of Serbia, Department of Chemistry, Njegoševa 12, 11000 Belgrade, Republic of Serbia.

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Summary

Imipramine solubility in aqueous solutions is complex due to aggregation and degradation. This study quantifies its solubility, aggregation constants, and salt properties, offering insights for drug development.

Keywords:
chloride saltcritical micellar concentrationpH and buffer effectpH-ramp shake-flask methodphosphate saltsolubility product

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Area of Science:

  • Pharmaceutical Sciences
  • Physical Chemistry
  • Drug Discovery

Background:

  • Imipramine, a tricyclic antidepressant, exhibits pH-dependent solubility complicated by aggregation in acidic and degradation in alkaline conditions.
  • Accurate solubility data is crucial for understanding drug behavior in aqueous media, impacting formulation and therapeutic efficacy.

Purpose of the Study:

  • To comprehensively investigate the pH-dependent solubility of imipramine and its hydrochloride salt in various aqueous media.
  • To characterize solid-phase transformations and determine key equilibrium constants, including intrinsic solubility, solubility products, and aggregation constants.
  • To provide valuable data for early-stage drug discovery and formulation optimization of tricyclic antidepressants.

Main Methods:

  • Utilized the pH-ramp shake-flask method for solubility determination.
  • Employed the computer program pDISOL-X for experimental design, data processing, and equilibrium constant refinement.
  • Characterized solid precipitates using thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analysis.
  • Determined critical micelle concentration via conductometric titrations.

Main Results:

  • Detailed imipramine pH-solubility profiles revealed complex aqueous equilibria and solid-phase transformations.
  • Quantified intrinsic solubility, solubility products of imipramine hydrochloride and phosphate salts, and aggregation constants (trimer, heptamer, phosphate complex).
  • Solid-state characterization results corroborated the pDISOL-X analysis.

Conclusions:

  • Subtle structural variations among tricyclic antidepressants significantly influence their aqueous media behavior.
  • The determined solubility and aggregation data are valuable for drug discovery, formulation, and in vitro/in vivo studies.
  • Understanding these physicochemical properties is essential for optimizing the development and application of imipramine and related compounds.