EFFECT OF EXCIPIENTS AS PRECIPITATION INHIBITOR ON PHASE TRANSFORMATION AND DISSOLUTION PROFILE OF CARBAMAZEPINE-SACCHARIN COCRYSTAL TABLETS

• Main Author: Pratiwi, Novita
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/80361
• Institution: Institut Teknologi Bandung

Poorly water-soluble drugs present ongoing challenges in translating them into viable medicinal products. Oral absorption of poorly soluble drugs may be incomplete, variable, and less than proportional to dose. To overcome limited oral absorption, currently many medicinal ingredients are being developed as supersaturated active pharmaceutical ingredients (sAPI), such as cocrystals, salts, metastable crystalline forms, and amorphous solid forms. For nonionized drugs, one alternative is to form cocrystals. The solubility advantage of pharmaceutical cocrystals at supersaturation concentrations presents the risk of precipitation to less soluble crystalline forms during the dissolution process due to the solution-mediated phase transformation (SMPT) phenomenon. The strategy is to include precipitation inhibitor polymers (PPIs) in the formula, HPMC being one of the most effective PPIs in inhibiting drug precipitation and improving dissolution behavior as well as maintaining cocrystal supersaturation. The aim of this research was to determine the effect of the single excipient HPMC and the combination excipient HPMC + MCC and HPMC + primojel as precipitation inhibitors on the phase transformation and dissolution profile of cocrystals in tablets. This study highlights the importance of exploring cocrystal form conversion in aqueous media and illustrates the potential for simple formulations that can be produced based on an efficient and material-saving approach. Carbamazepine cocrystal (CBZ III) and saccharin coformer (SAC) were chosen as model compounds for this study because of their tendency toward precipitation. The results of this study indicate that the use of combined excipients (HPMC + MCC) and (HPMC + primojel) does not show a significant synergistic effect in inhibiting precipitation and increasing the solubility and dissolution of CBZ-SAC cocrystals. The use of a single excipient HPMC with a concentration of 6.5% (w/w) in CBZ-SAC cocrystal tablets shows a dissolution profile that meets the dissolution requirements of test 2 according to the monograph where the amount of substance dissolved at 15 minutes is in the range of 45 – 75% and at 60 minutes not less than 75% and is supported by good flowability and tabletability.