Effects of formulation and process variables on the release of a weakly basic drug from single unit extended release formulations

A new commercially available extended release matrix material, Kollidon® SR, composed of polyvinylacetate (PVA) and polyvinylpyrrolidone (PVP), was evaluated with respect to its ability to modulate the in vitro release of the weakly basic drug ZK 811 752. The effect of different formulation and process parameters on the release kinetics of ZK 811 752 from PVA/PVP based matrix tablets was investigated as a function of the (i) nature of excipient added to the drug-polymer mixtures, (ii) method of manufacturing (direct compression versus wet granulation), and (iii) effect of a post-compression curing step. ZK 811 752 containing extended release matrix tablets were successfully prepared by using Kollidon® SR. The drug release from the matrix tablets increased by the addition of excipients such as maize starch, lactose and calcium phosphate. Addition of the highly swellable maize starch and the water-soluble lactose accelerated the drug release in a more pronounced manner compared to the water-insoluble calcium phosphate. Compound release from matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression. Post compression curing did not influence the drug release rate from drug-lactose-Kollidon® SR formulations. Stability studies demonstrated no degradation of the drug substance and reproducible drug release patterns for matrix tablets stored at 25 °C/60% RH and 30 °C/70% RH for up to 6 months.