The improvement of aqueous chemical stability of a model basic drug by ion pairing with acid groups of polyelectrolytes

• Published in: International journal of pharmaceutics Vol. 269; no. 1; pp. 149 - 156
• Main Authors: Jimenez-Kairuz, A.F., Allemandi, D.A., Manzo, R.H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09.01.2004; Elsevier
• Subjects: Acrylic Resins - chemistry; Biological and medical sciences; Carbomer hydrogels; Chemical stability improvement; Drug Stability; Excipients - chemistry; General pharmacology; Hydrogels - chemistry; Hydrogen-Ion Concentration; Hydrolysis; Ions; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyelectrolyte stabilizing effect; Polyelectrolyte–drug interaction; Procaine - chemistry; Procaine stability improvement; Solubility; Time Factors; Water - chemistry; Carbomer hydrogels; Procaine stability improvement; Chemical stability improvement; Polyelectrolyte–drug interaction; Polyelectrolyte stabilizing effect; Polyelectrolyte-drug interaction; Interaction; Chemical stability; Colloidal gel; Local anesthetic; Polyelectrolyte; Ester; Basic compound; Carbomer; Procaine; Hydrogel; Aqueous solution
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2003.09.008

Carbomer (C) and procaine (P) were selected respectively as models of polyelectrolyte (PE) and basic drug (B) of low stability in aqueous solution. The purpose of this investigation was to test if a (C–P) aqueous system provides a microenvironment in which P is less exposed to hydroxyl ion catalyzed degradation, its main degradation pathway over a wide pH range. It was determined that in (C–P) a high fraction of P was present in the form of ion pairs [RCOO −PH +] with the carboxylate groups of C. The [RCOO −PH +] fraction was above 97% for compositions containing higher than 50 mol% of P. The chemical stability of C–P was assayed at two selected pHs (7.5 and 8.5) in comparison with conventional reference solutions (RS) without C. Procaine in (C–P) was 4.2 and 6.2 times more stable than in its respective RS at the two conditions assayed. The stabilizing factor was calculated as the ratio of the rate constants k obs RS/ k obs C–P. Since C–B systems exhibit negative electrokinetic potential that attracts positive ions such as (H +) and repels negative ones such as (OH −), the stabilizing effect would be associated with the higher acidity of (C–P) environment, in which PH + molecules attached to the PE should also have lower kinetic energy than those in the bulk medium.