CHARACTERIZATION ON PHYSICAL PROPERTIES OF BINARY SYSTEM OF ACETAMINOPHEN-METOCLOPRAMIDE HCL MONOHYDRATE AND THEIR CHANGES DURING THE MILLING PROCESS

• Main Author: Prasetya Nugraha, Yuda
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45238
• Institution: Institut Teknologi Bandung

Pharmaceutical formulations containing two active pharmaceutical ingredients (API) are generally intended to provide a synergistic effect or to reduce side effects. However, the combination often create problems in both pharmaceutical and pharmacological aspects because of the incompatibility between the two APIs or between the API and excipients. The incompatibility may either be physical or chemical interactions that occur either in the development process of the preparation or during storage. Although the combination of acetaminophen (PCT) and metoclopramide HCl monohydrate (MCP) has advantages in terms of pharmacokinetics and pharmacology, pharmaceutical characterization needs to be carried out. PCT and MCP have the same monoclinic crystal structure. In addition, both APIs have functional groups that can interact with each other. Milling is a process that involves mechanical energy and can cause undesirable changes in the physical or chemical characteristics of compounds. The aim of this study was to characterize the physical properties of the PCT-MCP binary system and their changes during the milling process using cold contact method, a thermal method (Differential Scanning Calorimetry), microscopy (polarizing microscopy and Scanning Electron Microscope), Raman spectroscopy, and diffractometry (Powder X-Ray Diffraction). The milling process was performed using mortar grinding, neat grinding and solvent drop grinding mills. On the cold contact method, the presence of crystals of different habits at the contact area was not observed. The DSC thermogram of equimolar PCT-MCP binary mixtures indicated there were no interaction between PCT and MCP. Aggregation of particles occurred during the milling of PCT and MCP for 60 minutes with a mortar grinder mill. The milling of equimolar PCT-MCP binary mixture with a mortar grinder mill for 5 minutes resulted in a decrease in the crystallinity index of 84.4 %, significantly more than during the milling of each component for 60 minutes (34.10 % and 37.76 % respectively). The diffractogram peak broadening resulted from the milling of the mixture for 5 minutes were more significant than the peak broadening from the milling of individual components for 60 minutes. Neat grinding and solvent drop grinding did not result in changes in the Raman spectrum and diffractogram of an equimolar PCT-MCP binary mixture which indicates that there were no interaction between PCT and MCP.