FORMULATION AND IN VITRO CHARACTERIZATION OF SUSTAINED RELEASE TABLET FROM PELLET CONTAINING BIOACTIVE FRACTION OF \TEXTIT{LUMBRICUS RUBELLUS}

• Main Author: Christy, Gabriela
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78546
• Institution: Institut Teknologi Bandung

DLBSI 033F is a bioactive fraction derived from Lumbricus rubellus earthworm extract that possesses an antithrombosis and thrombolytic activities. This bioactive fraction contains a potent fibrinolytic enzyme with excellent specificity to fibrin. The development of DLBS1033F into an oral dosage form would be very favorable for the treatment of thrombosis and thrombosis-associated diseases. This research aims to formulate a multiparticulate sustained release system of DLBS 1033F tablet, which targeted the release of this bioactive fraction to the small intestine and colon segment of gastrointestinal tract. In these gastrointestinal segment, the chemical and physical stabilities of the fibrinolytic enzyme can be maintained due to the more neutral pH and lowpr proteolytic enzymatic activity. The sustained release system was aimed to maintain the effective concentration of the bioactive in the bloodstream, so longer duration of therapy can be achieved. The delayed and sustained release system incorporated into the formula by the development of matrix system. Pellets containing DLBS1033F were first prepared by extrusion-spheronizalion methods An optimization was done to modify the protein release by using guar gum and a combination of sodium alginate and calcium acetate. Evaluation studies were performed to select the best pellet formula for the next compression process. Pellet formula containing 60% DLBS1033F, 5% sodium alginate, 5% calcium acetate, 25% Avicel PHIOI, and 5% PVP showed the best physical characteristic and in vitro release profile. About of protein was released from the pellet for 2 hours of release study in the HCI pH 1.2 medium, and about 90.53±1.47% of protein was then released at the end of 8 hours study after changing the medium into pH 6.8 phospate buffer solution. Tablet containing DLBS1033F pellets was then prepared by direct compression method. Xanthan gum was introduced into the tablet formula to achieved better sustained release profile for 24 hours. Based on in vitro release study, multiparticulate tablet formula containing 30% pellets and 20% xanthan gum showed the best sustained release profile. About of protein was released from the tablet for 2 hours of release study in the HCI pH 1.2 medium, and about 85.96±2.43% of protein was then released at the end of 24 hours study after changing the medium into pH 6.8 phospate buffer solution. Both of the chosen pellet and tablet formulas showed a good protein profile similarity with the DLBSI 033F powder from the SDS-PAGE analysis. The protease activity of the multiparticulate tablet was 2881.98±2176 U/mg protein. Thus, the developed formula enabled to prevent the protein release in the gastric segment and sustain the drug release for 24 hours in lower part of GIT.