Pharmaceutica Analytica Acta

DoE for identification of incompatibilities in formulation development

4^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 24-26, 2014 Hilton San Antonio Airport, San Antonio, USA

Pawel Stasiak, J Linek, P Hanzlik, O Dammer, M Tkadlecova and A Dumicic

Posters: Pharmaceut Anal Acta

Abstract:

Design of experiments (DoE) has been used to investigate stability issue of hydrochloride salt of an active compound (API) converting into weak base in tablets. Compatibility studies of an API with excipients (cellulose microcrystalline, talc, stearic acid and magnesium stearate) at different ratios were designed and magnesium stearate was identified as responsible factor. Using 13C ssNMR it was proven that base formation depends on concentration of magnesium stearate. Level of the API base similar to observed in the reference product (20-30% in stress conditions, 64h, 80?C) was measured only at 0.25% concentration of magnesium stearate and was significantly higher at higher concentrations of magnesium stearate. For technological reasons, the lubricant was replaced with its acidic counterpart at a concentration of 4% which resulted in formation of less than 10% base in stress conditions. Long-term stability of the product has been already confirmed in registration batches. Reasonable DoE application allowed for fast and effective identification of instability factor and resulted in development of a stable product over entire shelf-life.

Biography :

Pawel Stasiak has completed his Ph.D. in Pharmaceutical Technology from Medical University of Gdansk (Poland) in 2009 and Euro-Ph.D. in Advanced Drug Delivery in 2010. Currently he is a Formulation Leader at Zentiva k.s, Prague (Czech Republic).