Study of interaction between croscarmellose and escitalopram during sample preparation.
During routine analysis of an escitalopram tablet formulation, it was seen that there was a systematic deviation between content uniformity (CU - one tablet analysis) and assay analysis (ten pooled tablets). In the presence of the excipients from the tablet, it was found that the extraction of the active pharmaceutical ingredient (API) was incomplete. It was shown that the commonly used tablet disintegrant croscarmellose sodium (crosslinked carboxy-methyl cellulose) had a significant interaction with escitalopram. This was later found to be the explanation for the lower extraction during assay testing. Under normal conditions, the extraction took place in acidic medium which caused protonation of the amine and thereby the interaction of charged species in solution. The interaction of API was studied further with pure croscarmellose and the entire tablet matrix. A range of conditions was considered, including altering extraction volumes, organic solvents, pH of the extraction solvent, and addition of competitive binder in various concentrations. It was seen that arginine was the most effective cationic competitive binder of those tested and that adding it at a suitable concentration level could significantly improve the analytical methods. In the present case, an improvement in recovery was from 98.5% to almost 100% was achieved.
H. Lundbeck A/S, Valby, Denmark. jetl@lundbeck.com
Jesper
J
Larsen
Claes
C
Melander
D000588:Amines / Q000737:chemistry; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015283:Citalopram / Q000737:chemistry*; D004347:Drug Interactions; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013607:Tablets / Q000737:chemistry
D000588:Amines; D005079:Excipients; D007477:Ions; D012996:Solutions; D012997:Solvents; D013607:Tablets; D015283:Citalopram; D002266:Carboxymethylcellulose Sodium