Buffer Effects on Drug Release Kinetics From Acidic Hydrophobic Gel Discs
Aracely Serrano–Medina and José Manuel Cornejo–Bravo*
Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, Calzada Universidad 14418, Parque Industrial Internacional, Mesa de Otay, Tijuana B.C. Mexico, 22300. *E–mail: jmcornejo@uabc.edu.mx
Received June 14, 2010.
Accepted October 4, 2010.
Abstract
Here we study the variability of drug release rates from hydrophobic polyacid gels, due to the presence of basic buffer species. Release kinetics of the model drug salicylic acid from crosslinked poly(methyl methacrylate–co–methacrylic acid) hydrogels were measured as a function of buffer concentration, buffer acidity (pKa), and solution pH, with total ionic strength (I) held constant. Results show that the release rate of salicylic acid is determined by the concentration of buffering species in the nonionized, conjugated basic form, and not by the pH itself. Since it is difficult to control the concentration and composition of weak electrolytes in the gastrointestinal tract, precise pH–modulated controlled release from hydrophobic polyacid gels may be difficult to achieve. These gels may be more suitable in cases where pH–triggered release is desired, but precise rate control is not warranted.
Keywords: hydrogel, polyelectrolyte gel, swelling–controlled release, buffer effect, methacrylates.
Resumen
En el presente trabajo se estudia la variabilidad en la velocidad de liberación de fármacos a partir de geles hidrofóbicos poliá–cidos debida a la presencia de amortiguadores básicos. Se evaluó la cinética de liberación del fármaco modelo ácido salicílico, a partir de hidrogeles entrecruzados de poli(metacrilato de metilo–co–ácido metacrílico), como función de la concentración de amortiguador, la constante de acidez (pKa) del amortiguador utilizado y el pH de la solución, manteniendo constante la fuerza iónica. Los resultados demuestran que la velocidad de liberación del ácido salicílico está determinada por la concentración de las especies amortiguadoras en la forma no ionizada (base conjugada) y no en el pH por si mismo. Los resultados implican que es difícil modular la liberación de fármacos modulada por el pH a partir de geles hidrofóbicos poliácidos, debido a la variabilidad en la concentración y composición de electrolitos débiles (amortiguadores) en el contenido intestinal. Estos geles tienen aplicación para liberación de fármacos iniciada por pH alcalinos, pero no se puede asegurar control de la liberación.
Palabras clave: hidrogel, gel polielectrolítico, liberación controlada, efecto de amortiguadores, metacrilatos.
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]]>Acknowledgments
This work was supported by grants from SEP–CONACYT (2002–CO1–40262), CONACYT (90274), and from the Universidad Autónoma of Baja California (13th internal call for research projects support 3863). The authors gratefully acknowledge Professor Mario Del Valle for proof–reading the manuscript of this article.
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