LITERATURE REVIEW OF NSAID COCRYSTALS AND PILOT SCALE EXPERIMENT OF SODIUM MEFENAMIC NICOTINAMIDE AS POTENTIAL SALT COCRYSTAL

• Main Author: Desti Parwati, Rismaya
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/56616
• Institution: Institut Teknologi Bandung

ii The formation of cocrystal can modulate active pharmaceutical ingredients with poor physicochemical and solid physical properties. This study aims to conduct a literature review on the development of nonsteroid anti inflammation (NSAID) cocrystal in general and to conduct pilot scale-up experiments of sodium mefenamic nicotinamide (SMN) cocrystal salt. This literature review describes the progress and challenges that occur in the development of NSAID cocrystal. Sources of information were obtained by using “NSAID co-crystalline”inclusion criteria through search engines, namely ScienceDirect, Google Scholar, PubMed, American Chemical Society (ACS) publication. Based on the literature review, it was known that researches on NSAID cocrystal have been developed in various methods to produce better cocrystal. In the development of NSAID cocrystal, there are many challenges, such as coformer selection, improvement of solubility and intrinsic dissolution rate, changes in pH, changes instability, and formation of polymorphisms. In this experiment, scaling up was carried out with the solvent drop grinding (SDG) method using a blender with a capacity of 5g, 10g, 25 g to produce a solid sample of 100 g. The SDG method was chosen because it can produce homogeneous cocrystal faster, easier, and less expensive; with maximum yield, and reducing the use of organic solvents compared to the solvent evaporation (SE) method. Ethanol was chosen because it is most safe compared to other organic solvents. Optimization of the SDG method with the blender was carried out to obtain the mixing technique, the amount of solvent, and the best time. The results of the scaleup were then characterized by solid analysis using thermal analysis (electrothermal and DSC), FTIR, and PXRD. Furthermore, the characterization of powder was carried out by testing the flow rate and compressibility of the SMN 25 g. Based on the results of the research, the SMN scale-up method with a blender can be done by directly mixing mefenamic acid, sodium hydroxide, and nicotinamide equimolar ratio 1: 1: 1 with the amount of solvent (70% ethanol) 3 mL for 5g SMN in a blender time of 1 minute, 7 ml. for 10g SMN and 14.2 ml for 25g SMN in 4 minutes. Characterization and evaluation of solids concluded that the scale-up of SMN could be formed by mechanical methods using SDG using a blender with better flow properties and compressibility compared to sodium mefenamic salt (SM).