Evaluation of matrices containing molecularly imprinted polymers in the enantioselective-controlled delivery of beta-blockers.

Granules and beads of methacrylic acid (MAA) and granules of N-acryloyl-alanine polymer (NAA) were produced using ethylene glycol dimethacrylate as cross-linking monomer either by bulk (in the case of granules) or suspension (in the case of beads) polymerization. Either R- or S-propranolol, were used as an imprint molecule, acting as a template, with a view to conferring enantioselectivity of release upon the polymer. The molecularly imprinted polymers (MIPs) or nonMIPs (control) were formulated with racemic propranolol and other excipients and compressed to form matrix tablets. Enantioselective release of propranolol in vitro was monitored using a stereoselective HPLC assay. The influence of the method of polymer synthesis, drug: polymer ratio, pH and temperature on the release of the two enantiomers was determined. Stereoselectivity of release was identified in tablets containing either MAA or NAA granules or MAA beads, with the latter showing the greatest differences between enantiomers. Release of the enantiomer used as the print was always faster than the release of the nonprint enantiomer. In the case of S-propranolol-MIP bead matrices composed of MAA, greater differences in the release of enantiomers could be promoted by increasing the polymer: drug ratio of the tablet. Differences in the release rate of the two propranolol enantiomers was still apparent as the pH was varied between 3 and 7.4 and when the temperature was decreased from 37 to 25 degrees C. S-Propranolol-MIP bead matrices demonstrated cross-reactivities of stereoselective dissolution for enantiomers of pindolol and oxprenolol, both of which have structural similarities to the imprint molecule. It is concluded that polymers of this type may have great potential in controlling, via means of formulation, the release of drug eutomer whilst enhancing retention of distomer in the dosage form.