DLBS1033 is a mixture of bioactive proteins fractinated from the earthworm Lumbricus rubellus which possesses antithrombotic and thrombolytic activities. DLBS1033 contains a potent fibrinolytic enzyme with excellent specificity for fibrin. A commercial oral enteric coated tablet for administration 3 times daily is available on the market from the DLBS manufacturer. This research aimed to develop a multiparticulate sustained-release DLBS1033 Forte (DLBS1033F) tablet (with more potent fibrinolytic activity than DLBS1033), which has targeted release in the small intestine and colon. The chemical and physical stability of the fibrinolytic enzyme was expected to be preserved in these bowel segments. The sustained-release system was designed to maintain the effective plasma concentration of the proteins and prolong the thrombolytic activity. This was done by incorporating the proteins in a multiparticulate solid that was subsequently compressed into the monolithic system of a sustained-release tablet. The challenge was to maintain pellet integrity after the compression process. A set of studies confirmed the preserved physical shape of the pellets. In addition, in vitro release studies of the multiparticulate tablet in reassembling media of the gastrointestinal tract indicated the successful formulation of DLBS1033F as an enteric as well as sustained-release solid dosage form.