Drug release from complexes with a series of poly(carboxyalkyl methacrylates), a new class of weak polyelectrolytes

• Published in: International journal of pharmaceutics 2005-11, Vol.305 (1), p.52-60
• Main Authors: Cornejo-Bravo, Jose M., Flores-Guillen, Maria E., Lugo-Medina, Eder, Licea-Claverie, Angel
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cations; Delayed-Action Preparations - chemistry; Diltiazem - chemistry; General pharmacology; Hydrogen-Ion Concentration; Hydrophobic; Hydrophobic and Hydrophilic Interactions; Ion exchange; Kinetics; Medical sciences; Methacrylates; Osmolar Concentration; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyamines - chemical synthesis; Polyelectrolyte; Polymethacrylic Acids - chemical synthesis; Propranolol - chemistry; Solubility; Structure-Activity Relationship; Sustained drug release; Tablets; Temperature; Verapamil - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.08.023

Carboxyalkyl methacrylates, a new class of non-cross-linked, hydrophobic weak polyelectrolytes, were synthesized, and then bound to cationic drugs (propranolol·HCl, diltiazem·HCl and verapamil·HCl) to form water-insoluble complexes that release the bound drug only in ionic media (pH 7.4). Compressed tablets were prepared from these cation exchange polyelectrolytes. Release profiles followed zero order kinetics ( n > 0.90; n is the release exponent). As the hydrophobicity of the polyelectrolytes increased, the rate of release decreased and deviated from linearity ( n = 0.7). Both the ionic strength of the medium as well as the solubility of the drug affected the rate of release. In acidic media (pH 1.2) a burst of drug was released but the release was halted by a layer of non-ionized polymer precipitated on the surface of the tablets. The results indicate that it is possible to “tailor-make” the release kinetics by using a polyelectrolyte from the series with the suitable hydrophobicity.