Development and in-vitro/in-vivo evaluation of extended release propranolol tablets Part II: pilot bioequivalence study

In this second part of the study an optimized propranolol (CAS 318-98-9) extended release matrix tablet based on polyvinylacetate/povidone excipient was tested and compared with an extended release marketed capsule product. Using the USP dissolution testing, the drug release from the matrix tablets was faster in the initial acid stage, but similar in the buffer stage to that of the market capsule product. When evaluated in a pilot bioequivalence study in eight human volunteers, the two products were not bioequivalent according to the FDA bioequivalence criteria. The matrix tablets produced higher C-max and AUC(0-24h) than the market capsules. For the developed tablet formulation the higher initial plasma concentrations correlated positively with the faster initial release observed during in vitro testing. Stability study of the matrix tablet formulation indicated a significant reduction in dissolution rates associated with an increase in tablet hardness under accelerated conditions. However, stability testing under ICH long-term conditions did not influence the physical properties and dissolution characteristics of the tablets. Storage of these tablets must be carried out under controlled temperatures not exceeding 25 degrees C / 60 % RH. Thus, the newly introduced polyvinylacetate/povidone excipient succeeded in developing propranolol extended release matrix tablets.