New drug salt formation in biodegradable microspheres

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Microsphere drug delivery systems are crucial for controlled release.
• The oil-in-water (O/W) emulsion method is a common technique for microsphere preparation.
• Understanding factors influencing drug encapsulation is vital for optimizing formulations.

Purpose of the Study:

• To investigate the impact of inorganic salts in the external phase of O/W emulsions on microsphere preparation.
• To explore the formation of new drug salts during the encapsulation process.

Main Methods:

• Poly(D,L-lactic acid) microspheres containing quinidine sulfate were prepared using the O/W emulsion method.
• Various inorganic salts were incorporated into the external phase.
• Drug loading was quantified using UV spectrophotometry.
• Drug salt anions within microspheres were analyzed via ion chromatography.

Main Results:

• The use of salts with anions uncommon to the drug salt resulted in the formation of new drug salts within the microspheres.
• Drug loading increased significantly with the addition of NaClO4 or NaSCN.
• The fraction of the drug as a new salt correlated linearly with drug loading.
• Increased organic solvent volume or decreased cosolvent polarity led to a higher new salt fraction and reduced drug loading.

Conclusions:

• Introducing inorganic salts with non-common anions in the O/W emulsion method promotes the formation of new drug salts.
• The degree of new drug salt formation is influenced by salt concentration, cosolvent characteristics, and polymer concentration.