STUDY OF PHYSICAL INTERACTION ALBENDALOLE-CARBOXYLIC ACID AND THEIR EFFECT ON SOLUBILLITY

• Main Author: Fatmawati, Sofia
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78784
• Institution: Institut Teknologi Bandung

Background : Albendazole is a benzimidazole anthelmintics that has a very low solubility, high permeability, and classified as a BCS class Il substance. Physical and chemical interaction can occur between active pharmaceutical ingredient (API) with API or with excipients. The interaction affects the physicochemical properties of drugs. Interaction of albendazole with carboxylic acid formation to enhance its solubility has not been reported previously. This study aimed to observe the interaction of albendazole (ABZ) with benzoic acid (BA), tartaric acid (TA), nicotinic acid (NA), malonic acid (MNA), sbrbic acid (SA), citric acid monohydrate (CA), and maleic acid (MA); next to study their effect on solubility improvement. Methods: Firstly, this study was conducted by arrange the phase diagram of melt temperature of the mixtures from the two components, in the ratios 0:10; 1: 9; 2: 8; • 10:0, which were measured by Electrothermal 9100. Preliminary screening was conducted by DSC to physical mixture in ratio 1:1. Next, selected carboxylic acids and albendazole (l : l) were ground using ball mill for further screening. Albendazole with selected carboxylic acid (l : l) interaction was tried to isolate by solvent evaporation method using methanol. Next, the interactions were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD) and Fourier Transform Infrared Spectroscopy (FTIR). Afterwards, solubility analysis of physical interaction was measured and analyzed using UV spectrophotometer. Results: Phase diagram and DSC data showed that ABZ did not interact with BA, but had eutectic interaction with NA and TA with the eutectic temperature 178,9 and 160 cc, thoroughly. Different diffractogram patterns showed from the ball milled result of ABZ mixed with CA or MA. Recrystallization form ABZ with CA or MA in methanol caused polymorph change of ABZ form I to Il, with the typical peaks showed at 20: 24,66 and 25,540, and the melting point at 175 oc. Furthermore, the result showed that solubility of ABZ with CA and MA increased in water and HCL 0, I M. Conclusion: Albendazole do not interact with benzoic acid, malonic acid, and sorbic acid, but indicates to form an eutectic interaction with nicotinic acid and tartaric acid with eutectic temperatures were 178,9 and 160 oc, thoroughly. Albendazole does not interact with citric acid and maleic acid after ball milling, but shows polymorphism change after recrystallization from - methanol. Albendazole with citric acid and maleic acid have higher solubility as two to five fold in water, and four to eight fold in HCL 0, I M, thoroughly, than alberp4qzole itself.