New drug salt formation in biodegradable microspheres.
OBJECTIVE
To investigate the effects of inorganic salts in the external phase of an oil-in-water (O/W) emulsion method during microsphere preparation.


METHODS
An O/W emulsion method was used to prepare poly(D,L-lactic acid) microspheres containing quinidine sulfate. Different inorganic salts were used in the external phase during microsphere preparation. Microsphere drug loading was determined by UV and the drug salt anions inside the microspheres were determined by ion chromatography.


RESULTS
New drug salts were formed during encapsulation in the microspheres when salts with non-common anions to the drug salt were used. Drug loading increased when NaClO4 or NaSCN were used. The fraction of drug as the new salt in microspheres increased non-linearly with the salt concentration in the external phase, however, the fraction of drug as the new encapsulated salt was linearly related to drug loading. Drug loading decreased and new salt fraction increased with increasing organic solvent volume or with decreasing cosolvent polarity.


CONCLUSIONS
Introducing salts containing non-common anions to the drug salt employed in the external phase of O/W emulsion microsphere method leads to new salt formation. The extent of new drug salt formation is affected by salt levels added, cosolvent type and polymer concentration.
Al-Maaieh
Ahmad
A
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. al-maaieh_ahmad@lilly.com
Flanagan
Douglas R
DR
D000838:Anions / Q000032:analysis; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations / Q000737:chemistry; D004655:Emulsions; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009994:Osmolar Concentration; D010472:Perchlorates / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011802:Quinidine / Q000737:chemistry*; D012492:Salts / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013861:Thiocyanates / Q000737:chemistry; D013997:Time Factors
D000838:Anions; D003692:Delayed-Action Preparations; D004655:Emulsions; D010472:Perchlorates; D004364:Pharmaceutical Preparations; D011091:Polyesters; D011108:Polymers; D012492:Salts; D012997:Solvents; D013861:Thiocyanates; D019344:Lactic Acid; C033616:poly(lactide); D011802:Quinidine