Enhanced and retarded drug release from hydrophobic ionic beads

The effect of drug solubility and drug loading on the kinetics of polymer ionization and drug release from poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been investigated. Acebutalol HCl, labetalol HCl, and propranolol HCl were chosen as model drugs, representing a range of liphophilicity. Polymer ionization and drug release rates increase with drug loading for a highly water-soluble drug, i.e., acebutalol HCl. Drug release and ionization rates, however, decrease with drug loading up to 11.0 and 12.2% for less water-soluble drugs, i.e., labetalol HCl and propranolol HCl, respectively, and then increase above the loading level of 18.6%. This decrease in rate is attributable to the low solubility of the drug, resulting in its slow diffusion and the need for increased electrolyte uptake to ionize the acidic components (i.e., polymer matrix and HCl). At a loading level below 18.6%, the ionization kinetics were governed by intraparticle diffusion and chemical reaction resistances, with an additional minor contribution from film diffusion resistance. At higher loading, above 24.6% of acebutalol HCl, however, the film diffusion resistance controlled the overall ionization kinetics of drug-loaded PMMA/MAA beads.