Effect of Drug Loading in Mesoporous Silica on Amorphous Stability and Performance

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Mesoporous silica (MS) is researched for drug encapsulation.
• High drug loading in MS may cause physical instabilities in the amorphous drug form.

Purpose of the Study:

• To evaluate the impact of drug loading levels in MS on amorphous celecoxib stability and dissolution.
• Investigate drug loadings below, at, and up to the pore filling capacity (PFC).

Main Methods:

• Determined monomolecular loading capacity (MLC) and PFC for celecoxib on MS ParteckSLC500.
• Analyzed drug-loaded MS formulations after preparation and 18 months of accelerated storage (40°C, dry/humid).
• Assessed amorphous form stability and dissolution profiles.

Main Results:

• MS preserved amorphous celecoxib for 18 months when loading was below PFC (<48.4 wt.%) and stored dry.
• Loading at PFC resulted in recrystallization even under dry conditions.
• All samples recrystallized under humid conditions.
• Freshly prepared formulations showed supersaturation; loadings below PFC achieved higher supersaturation (DS ~15) than at PFC (DS ~6).
• Amorphous formulations remaining stable post-storage exhibited unchanged release profiles.

Conclusions:

• Mesoporous silica can maintain amorphous celecoxib stability below PFC under dry conditions.
• Humidity and loading at PFC compromise amorphous drug stability.
• Drug loading impacts supersaturation and dissolution, with lower loadings offering enhanced performance.