Fabrication of aceclofenac nanocrystals for improved dissolution: Process optimization and physicochemical characterization

摘要

The purpose of the study is to optimize process variables and fabricate nanocrystals to improve dissolution rate of aceclofenac. Particle engineering was carried out to obtain pure drug nanocrystals of aceclofenac to overcome its poor dissolution behavior using different polymeric stabilizers. A Box-Behnken design was used to study the influence of process variables and further optimization was carried out. The physicochemical properties were evaluated including particle size distribution, powder X-ray diffractometry, scanning electron microscopy and dissolution studies. Preclinical investigation was also carried out in Wistar rats. All the identified process variables influenced the particle size and dissolution velocity of aceclofenac. Methyl cellulose (MC) and hydroxypropyl methyl cellulose (HPMC) were found very effective in preventing growth of crystals and improving the dissolution of aceclofenac. The optimized process variables predicted were 0.47%, 25 °C and 1070 rpm for stabilizer concentration, processing temperature and mixing speed respectively using MC as stabilizer. The optimized aceclofenac nanocrystals showed improved dissolution and reduced particle size (Q, = 87.27 ± 0.83% and Mz = 54.23 ± 3.24 nm). Preclinical investigation using Wistar rats revealed statistically significant improvement of efficacy of optimized nanocrystals in terms of percentage inhibition of paw edema induced by carrageenan challenge indicating enhanced bioavailability through improved dissolution of aceclofenac nanocrystals.