Cortisone and cortisol break hydrogen-bonding rules to make a drug-prodrug solid solution

Area of Science:

• Pharmaceutical Science
• Materials Science
• Crystallography

Background:

• Multidrug formulations offer therapeutic advantages but require stable compositions.
• Solid solutions provide stability and tunable stoichiometry for drug mixtures.
• Cortisone and hydrocortisone (cortisol) are structurally distinct steroid compounds.

Purpose of the Study:

• To create a stable drug-prodrug solid solution of cortisone and hydrocortisone.
• To investigate the formation and properties of this novel solid solution.
• To assess the impact on hydrocortisone's dissolution characteristics.

Main Methods:

• Preparation of the solid solution from solution.
• Supercritical CO2 assisted spray drying technique.
• Analysis of the crystalline phase and hydrogen bonding interactions.

Main Results:

• A new crystalline phase of cortisone-hydrocortisone solid solution was successfully prepared.
• Formation was achieved via solution and supercritical CO2 spray drying.
• Hydrocortisone violated established hydrogen bonding rules (Etter's rules) within the solid solution.
• The dissolution rate of hydrocortisone in the solid solution was nearly doubled.

Conclusions:

• A stable drug-prodrug solid solution of cortisone and hydrocortisone can be formed.
• This solid solution strategy significantly enhances hydrocortisone dissolution.
• The findings suggest potential for improved pharmaceutical formulations and drug delivery systems.