Hydrogen bonding with adsorbent during storage governs drug dissolution from solid-dispersion granules

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Poorly water-soluble drugs often exhibit limited bioavailability.
• Solid dispersion technology aims to enhance drug solubility and dissolution rates.
• Ternary solid dispersions incorporate a drug, a carrier, and an adsorbent to improve formulation stability and performance.

Purpose of the Study:

• Investigate the impact of storage on drug dissolution from ternary solid-dispersion granules.
• Elucidate the mechanisms governing changes in drug release over time.
• Determine the role of formulation components and drug properties in dissolution stability.

Main Methods:

• Hot-melt granulation was employed to create ternary solid-dispersion granules.
• Seven model drugs with varying chemical properties were incorporated.
• Gelucire 50/13 and polyethylene glycol (PEG) 8000 served as dispersion carriers, with Neusilin US2 (magnesium aluminosilicate) as the adsorbent.

Main Results:

• Two primary mechanisms influence drug dissolution: amorphous conversion via hydrogen bonding to Neusilin (increasing dissolution) and Ostwald ripening (decreasing dissolution).
• Drug solubility in the Gelucire carrier is critical in determining which mechanism predominates.
• The presence of a eutectic mixture in the molten state during storage facilitates molecular mobility for Ostwald ripening.

Conclusions:

• Drug dissolution from ternary solid-dispersion granules upon storage is governed by a balance between drug-Neusilin hydrogen bonding and Ostwald ripening.
• Formulation design must consider drug solubility and carrier properties to optimize long-term dissolution performance.
• Understanding these competing mechanisms is essential for developing stable and effective solid dispersion formulations.