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What is the true solubility advantage for amorphous pharmaceuticals?
1Pfizer Inc., Groton, Connecticut 66340, USA. bruno_c_hancock@groton.pfizer.com
Pharmaceutical Research
|June 28, 2000
Summary
Amorphous pharmaceuticals exhibit significantly higher solubility than crystalline forms, though experimental values are often lower than thermodynamic predictions. This difference highlights challenges in measuring amorphous drug solubility under equilibrium conditions.
Area of Science:
- Pharmaceutical Sciences
- Physical Chemistry
- Materials Science
Background:
- Amorphous pharmaceutical materials offer potential advantages in drug delivery due to enhanced solubility.
- Understanding the quantitative solubility difference between amorphous and crystalline drug forms is crucial for formulation development.
Purpose of the Study:
- To quantify the solubility advantage of amorphous pharmaceutical materials compared to their crystalline counterparts.
- To compare predicted solubility advantages with experimentally measured values.
Main Methods:
- Differential scanning calorimetry (DSC) was used to determine thermal properties of amorphous and crystalline drugs.
- Thermodynamic analysis was employed to predict amorphous solubility advantage as a function of temperature.
- Experimental aqueous solubilities of amorphous and crystalline drug forms were measured at various temperatures.
Main Results:
- Predicted solubility advantages for amorphous drugs ranged from 10 to 1,600 fold compared to crystalline forms.
- Experimentally measured solubility advantages were generally lower than predicted.
- The temperature dependence of solubility advantage for one compound was less than thermodynamically predicted.
Conclusions:
- Amorphous pharmaceuticals demonstrate a marked solubility advantage over crystalline forms.
- Experimental solubility advantages are often less than theoretical predictions due to challenges in achieving true equilibrium conditions for amorphous materials.
- Thermodynamic predictions offer valuable insights into the theoretical maximum solubility enhancement for amorphous drugs, indicating their dissolution driving force.