Understanding excipient-induced crystallization of spray-dried amorphous solid dispersion.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Amorphous solid dispersions (ASDs) are crucial for improving drug solubility and bioavailability.
• Excipient-induced crystallization is a major challenge affecting the stability and efficacy of ASDs in tablet formulations.
• Accurate prediction of drug-excipient interactions is vital for successful pharmaceutical development.

Purpose of the Study:

• To develop a practical screening approach for evaluating excipient-induced crystallization of amorphous compound-X (SDI-X) in tablet formulations.
• To compare the effectiveness of different methodologies in assessing SDI-X recrystallization.
• To elucidate the influence of excipient properties and physical contact on SDI-X crystallization.

Main Methods:

• Utilized three methodologies: binary powder mixtures, binary compacts, and bilayer tablets.
• Qualitatively and quantitatively evaluated SDI-X recrystallization with various excipients under accelerated storage conditions.
• Focused on the physical proximity and contact between SDI-X and excipients.

Main Results:

• Binary compacts accurately reflected drug-excipient contact in tablets, outperforming conventional binary blends in predicting crystallization risk.
• Crystallization was confirmed to initiate at the contact surface between SDI-X and excipients, as shown in bilayer tablets.
• Less hygroscopic excipients like mannitol and lactose induced significant crystallization, indicating excipient type and contact are more critical than moisture content.

Conclusions:

• Direct physical contact methods, such as binary compacts, are superior for assessing excipient-induced crystallization risk of SDI-X.
• Excipient type and the nature of the drug-excipient interface play a more significant role in inducing recrystallization than hygroscopicity alone.
• Careful consideration of study design, sample preparation, and excipient selection is essential for reliable drug-excipient compatibility assessments.