PRODUCTION, CHARACTERIZATION, DISSOLUTION AND DIFFUSION STUDY OF DICLOFENAC ACID-PROLINE NANOCOCRYSTAL

• Main Author: Nur Auli, Winni
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45810
• Institution: Institut Teknologi Bandung

Nanotechnology has been widely developed to improve the solubility of active pharmaceutical ingredients. Cocrystal discovery also has taken much attention in the drug design and development to improve physicochemical properties. A combination of the two techniques generates “nanococrystallization”, a new approach to obtain the superior character of drugs. Previously, a new diclofenac acid-L-proline cocrystal (DPC) arrangement have been reported. Present research attempted to develop a nanococrystal diclofenac acid-L proline (NDPC) and to evaluate its formation kinetics, stability, and dissolution-diffusion improvements. The nanococrystal production was optimized by both top-down and bottom-up techniques. The top-down technique is done through the wet milling procedure and neat grinding procedures, while the bottom-up technique is done through the inversion phase of the globule and fast evaporation procedures assisted microwaving. The NDPCs were then characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, binocular microscopy, powder x-ray diffractometry, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The kinetics of NDPC formation were determined by the difference in microwave time and were analyzed using Fourier transform infrared spectroscopy. Dissolution was tested by type 2 apparatus and diffusion was tested using Franz diffusion cells. Particle size stability and structure of NDPC spectra was tested at room temperature of 25±2°C and relative humidity of 80±5%. The bottom-up method by fast evaporation assisted microwaving provided the best nanococrystals with a mean diameter of 598.2±63.2 nm and a polydispersity index of 0.278±0.062. Nanococrystal formation indicated to follow first order kinetic. Dissolution percentage of NDPC increase by 1.32 folds in buffer pH 1.2; 1.14 folds in buffer pH 6.8; and 2.46 folds in buffer pH 7.4. Diffusion percentage of NDPC increase by 2.06 folds in buffer pH 6.8; and 1.71 folds in buffer pH 7.4. Finally, nanosized DPC was proven can be produced with still maintain the cocrystal structure by the method fast recrystallization assisted microwaving and showed the superior dissolution and in vitro absorption profile than conventional-DPC.