The improvement of aqueous chemical stability of a model basic drug by ion pairing with acid groups of polyelectrolytes.
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.
Jimenez-Kairuz
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AF
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Edificio Ciencias 2, Ciudad Universitaria, 5000 Córdoba, Argentina. alfejika@yahoo.com.ar
Allemandi
D A
DA
Manzo
R H
RH
D000180:Acrylic Resins / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007477:Ions; D011343:Procaine / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors; D014867:Water / Q000737:chemistry*
D000180:Acrylic Resins; D005079:Excipients; D020100:Hydrogels; D007477:Ions; D014867:Water; C006903:carbopol 940; D011343:Procaine