MODIFICATION OF PHARMACEUTICAL CHARACTERISTICS OF METOCLOPRAMIDE THROUGH MULTICOMPONENT CRYSTAL FORMATION

• Main Author: Annisa, Luthfi
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/70446
• Institution: Institut Teknologi Bandung

Metoclopramide is an antiemetic drug which is commonly used in patients undergoing surgery, chemotherapy, and radiotherapy. In previous studies, preparation, determination of crystal structure, and characterization of the physicochemical properties of metoclopramide hydrochloride salt (MCP.HCl) and its cocrystals (MCP.HC-OXA and MCP.HCl-GAL) were carried out, and the cocrystals were proven to improve the physicochemical properties of MCP.HCl. This research is aimed to explore the base form of metoclopramide (MCP) to produce new model compounds or multicomponent crystals. The presence of hydrogen bond donors and acceptors in the MCP structure increases the chances of forming multicomponent crystals. Therefore, our research at this stage of development was carried out to modify the pharmaceutical characteristics of metoclopramide (MCP) through the preparation of multicomponent crystals and to determine the relationship between the crystal structure and its physicochemical properties. The coformers chosen in this follow-up study were the same as in previous studies: oxalic acid (OXA) and gallic acid (GAL). Screening with binary phase diagrams showed that MCP had the potential to form multicomponent crystal with OXA and GAL in a molar ratio of 1:1. The liquid-assisted grinding (LAG) combination with the slurry method was successful in forming the combination of MCP and OXA, whereas the slurry approach was successful for the combination of MCP and GAL. The obtained solids were characterized by differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD). The analysis results confirmed the formation of multicomponent crystal from MCP-OXA and MCP-GAL. Our findings showed that metoclopramide muticomonent crystals or salts improved solubility, intrinsic dissolving rate, and tabletability compared to the base form. MCP with the two carboxylic acid derivatives has the potential to be further developed into pharmaceutical formulation.