Amorphous drug delivery systems: molecular aspects, design, and performance

Area of Science:

• Pharmaceutical Science
• Materials Science

Background:

• Modern drug discovery yields compounds with poor aqueous solubility and permeability, posing delivery challenges.
• Modulating solubility is more feasible than permeability for enhancing drug bioavailability.
• Amorphization and solid-state manipulation are preferred methods for improving solubility and delivery of poorly soluble drugs.

Purpose of the Study:

• To review amorphous drug delivery systems and their associated thermodynamic phenomena.
• To discuss the formation, solubility advantages, and stability of amorphous drugs.
• To explore pharmaceutical alloys (solid dispersions) for exploiting amorphous systems.

Main Methods:

• Discussion of thermodynamic phenomena (glass transition, fragility, molecular mobility, devitrification kinetics).
• Analysis of molecular-level interactions influencing amorphous drug properties.
• Review of carrier properties, drug release mechanisms, and kinetics in solid dispersions.

Main Results:

• Amorphous drug systems offer significant solubility advantages.
• Solid dispersions enable effective solubilization and stabilization of drugs.
• Understanding release kinetics improves performance predictability.

Conclusions:

• Amorphous drug delivery systems are crucial for overcoming poor solubility.
• Solid dispersions are a viable strategy for developing advanced amorphous formulations.
• Further research into barriers and in vivo performance is needed for amorphous delivery systems.