Diclofenac-proline nano-co-crystal development, characterization, in vitro dissolution and diffusion study

Nanotechnology has been widely developed to improve the solubility of active pharmaceutical ingredients. Co-crystal discovery has also taken much attention in drug design and development. A combination of the two techniques generates "nano-co-crystallization", a new approach to obtaining the superior character of drugs. Previously, a new diclofenac-proline co-crystal (DPC) arrangement has been reported. The present research attempted to develop a nano-diclofenac-proline-co-crystal (NDPC) and to evaluate its formation kinetics, and dissolution-diffusion improvements. Both top-down and bottom-up methods optimized nano-co-crystal production. The top-down technique was used through the wet milling procedure and neat grinding procedures, while the bottom-up technique was performed through the globule inversion phase and fast evaporation assisted microwaving. The NDPCs obtained were then characterized by dynamic light scattering, binocular microscope, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, powder x-ray diffractometry, and Fourier transform infrared spectrophotometry. The kinetics of NDPC formation was determined based on the difference of microwaving versus the co-crystal yield, which was analyzed using Fourier transform infrared spectroscopy. Dissolution was tested by type 2 apparatus, and diffusion was tested using Franz diffusion cells. The bottom-up method by fast evaporation assisted microwaving provided the best nano-co-crystal with a mean diameter of 598.2 +/- 63.2 nm and a polydispersity index of 0.278 +/- 0.062. Nano-co-crystal formation kinetic, which was evaluated by FTIR, indicated to follow first order. Finally, NDPC showed the superior dissolution and diffusion profile than conventional-DPC. In this study, we demonstrate a promising alternative for improving the dissolution and diffusion of the drug by nano-co-crystallization.