Effect of particle size reduction and crystalline form on dissolution behaviour of nimesulide

Abstract

The objective of this study was to develop and examine innovative and very simple and easily scalable techniques able to improve solubility and/or dissolution rate and thus oral bioavailability of nimesulide. Three different nimesulide batches were obtained by three different laboratory-scale methods: Method A (Batch A) used crystallization by solvent evaporation in a nanospray dryer, Method B (Batches G and GLN) involved cryo-milling, and Method C (Batch Neu) dispersed nimesulide in Neusilin(A (R)) UFL2. All the nimesulide batches were fully characterized for chemical stability, thermal behaviour, physicochemical and micromeritics properties, and intrinsic dissolution and particle dissolution rates. Batch A not only showed a good reduction in particle size but also exhibited a reduced degree of crystallinity by both differential scanning calorimetry and X-ray powder diffractometry, which could explain the increase in intrinsic dissolution rate (IDR) and particle dissolution. Batch GLN showed an acceptable increase in IDR, probably caused by a slight decrease in the degree of crystallinity, and good improvement in dissolution rate due to a certain decrease in particle size. Batches G and native crystals exhibited very close IDRs, while G showed somewhat higher particle dissolution, probably attributed to the particle size reduction. The dispersion of nimesulide in Neusilin UFL2 in a 1:6 drug-polymer ratio made it possible to recover anamorphous powder, as proven by thermal analysis and X-ray powder diffractometry, characterized by pronounced particle size reduction to nanometric dimensions. Both amorphous character and nanometric dimensions could account for the fastest particle dissolution during the first 10 min of the experiment. The stability study conducted according to the International Conference on Harmonization (ICH) confirmed the good chemical and physicochemical stability of all the batches

A survey and optical microscopy in pilot comparative analysis of generic and original nimesulide granules

“…Studying the nanocrystal structure of a nimesulide drug, the scientists found that better solubility of BCS Class II drugs (including nimesulide) in water can be achieved by reducing the particle size using nanotechnologies. It is also confirmed by R. Rascioni et al.’s study [ 40 ], which found a relation between the reduction of the nimesulide particle size and the increased dissolution rate.…”

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

“…Effective delivery of Biopharmaceutics Classification System class II active pharmaceutical ingredients (APIs), defined as having high permeability and low solubility, 1 is challenging due to their low bioavailability. 2 To enhance their bioavailability, several technologies have been examined, such as particle size reduction, [3][4][5] cyclodextrin complexes, 6 polymeric micelles, 7 freeze-dried liposomes, 8 solid lipid nanoparticles, 9 and amorphous solid dispersions (ASDs). 10,11 Among them, amorphous solids dispersions technology has been proved to be one of the promising solutions.…”

Pharmaceutical Particle Engineering via Nano Spray Drying - Process Parameters and Application Examples on the Laboratory-Scale

“…• inflammation (e.g. dexamethasone and azithromycin, or pain and fever reducer indomethacin and nimesulide) [16,31,45,47,48,53,55,64,71,[99][100][101],…”

“…• oral (e.g. poorly water-soluble drugs like diuretic furosemide [10], pain reducing nimesulide [100], blood vessels dilating nicergoline [67], fever reducing indomethacin [99], anti-inflammatory dexamethasone [46], or steroidal hormone mecigestone [109]),…”