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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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A solvent is a substance, most often a liquid, that can dissolve other substances. Here, the substance being dissolved is called a solute. When a solvent and a solute combine, they form a solution - a homogenous mixture of both the solvent and the solute. Water is a universal biological solvent. Its polar structure allows it to dissolve many other polar compounds. The ability of water to dissolve is governed by a balance between water molecules binding to each other and binding to the solute.
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Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

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Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
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The selection of a drug's delivery route depends upon its physicochemical properties, including lipid or water solubility and ionization, as well as the therapeutic requirement, such as immediate or sustained effect. These routes can be divided into three primary categories: enteral, parenteral, and topical.
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The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
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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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Co-Amorphous Versus Deep Eutectic Solvents Formulations for Transdermal Administration.

Yannick Guinet1, Laurent Paccou1, Alain Hédoux1

  • 1UMR 8207-UMET-Unité Matériaux et Transformations, Université de Lille, CNRS, INRAE, Centrale Lille, F-59000 Lille, France.

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Summary

Stabilizing amorphous ibuprofen in topical formulations is key for effective drug delivery. This study found that specific deep eutectic solvents and co-amorphous blends prevent ibuprofen recrystallization, enhancing skin penetration.

Keywords:
co-amorphouscryo-millingdeep-eutectic solventshydrogen-bondinglow-frequency Raman spectroscopy

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Physical Chemistry

Background:

  • Transdermal drug delivery offers an alternative to oral administration, minimizing side effects.
  • Optimizing topical formulations requires enhancing both drug permeation and physical stability.
  • Amorphous drugs, like ibuprofen, are prone to recrystallization, negatively impacting efficacy.

Purpose of the Study:

  • To investigate the physical stability of amorphous ibuprofen in novel topical formulations.
  • To explore stabilization strategies using deep eutectic solvents (DES) and co-amorphous blends.
  • To understand the mechanisms underlying ibuprofen recrystallization inhibition.

Main Methods:

  • Analysis of ibuprofen:L-menthol phase diagrams using low-frequency Raman spectroscopy.
  • Investigation of amorphous ibuprofen stability in thymol:menthol DES.
  • Preparation and characterization of arginine-ibuprofen co-amorphous blends via melting and cryo-milling.
  • Determination of glass transition temperatures (Tg) and analysis of hydrogen bonding interactions (Raman spectroscopy).

Main Results:

  • Ibuprofen recrystallization was observed in ibuprofen:L-menthol mixtures across various concentrations.
  • Amorphous ibuprofen demonstrated enhanced stability when formulated in thymol:menthol DES.
  • Melting-processed arginine-ibuprofen blends stabilized amorphous ibuprofen, while cryo-milled versions showed recrystallization.
  • Recrystallization inhibition was linked to the preferential formation of heteromolecular hydrogen bonds, preventing ibuprofen dimerization, irrespective of Tg.

Conclusions:

  • Thymol:menthol DES and melting-processed arginine-ibuprofen blends are effective in stabilizing amorphous ibuprofen.
  • Heteromolecular hydrogen bonding plays a crucial role in preventing ibuprofen recrystallization in topical formulations.
  • Findings provide insights for designing stable amorphous drug formulations for transdermal delivery.