| Development and in vitro / in vivo Evaluation of Extended Release Propranolol Tablets Part II: Pilot bioequivalence study*) Elena Draganoiu and Adel Sakr Industrial Pharmacy Program, University of Cincinnati, Cincinnati, Ohio (USA) Correspondence: Prof. Dr. Adel Sakr, College of Pharmacy, University of Cincinnati Medical Center, Cincinnati, OH 45267-0004 (USA), Fax +1 513 558 72 57, e-mail: Adel.Sakr@Uc.Edu
Dedicated to Prof. Dr. Wolfgang Suess, Chairman, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Leipzig (Germany), on the occasion of his 65th birthday
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 Cmax and AUC0-24h 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 C / 60 % RH.
Thus, the newly introduced polyvinylacetate/povidone excipient succeeded in developing propranolol extended release matrix tablets. Key words Bioequivalence • CAS 318-98-9 • Extended release tablets • Methacrylic acid copolymer • Propranolol • Polyvinylacetate/povidone excipient |
