The Effect of an Optimized Wet Milling Technology on the Crystallinity, Morphology and Dissolution Properties of Micro- and Nanonized Meloxicam

Abstract

This article reports on the effects of a new combined wet milling technique on the physicochemical properties of meloxicam (MEL). The influence of milling time on the particle size, the crystallinity, the morphology and the dissolution rate of MEL has been studied in the presence and absence of polyvinyl alcohol (PVA) as a stabilizer agent. Micronized MEL particles were produced in aqueous medium which did not contain additive after milling for 10 min. For nanonization an additive and longer milling time were required. After particle size determination the structural and morphological characterization of the wet milled, dried products containing MEL were studied. X-ray powder diffractometry (XRPD) and differential scanning calorimetry (DSC) examinations revealed the change in the crystallinity of MEL. Scanning electron microscopy (SEM) images showed that aggregates of nanosized MEL particles were formed, regardless of the presence of PVA. The nanonized MEL crystals (D 50 = 126 nm) exhibited a regular shape and a smooth surface. The increased specific surface area resulted in a high dissolution rate and concentration of free MEL. According to the results, the produced samples could be applied as a basic material (micronized MEL) and intermediate product (micronized and nanonized MEL with PVA) for the design of dosage forms.

Production of meloxicam suspension using pulsed laser ablation in liquid (PLAL) technique

“…The crystal structure of meloxicam didn't change during the ablation process, and only a slight decrease in the crystalline fraction was observed. The amorphization of meloxicam could also increase the dissolution rate and improve the bioavailability of the poorly water soluble drug (especially if accessing the nanometer size range as well) [55].…”

Design and characterization of loratadine nanosuspension prepared by ultrasonic-assisted precipitation

“…The drug compounds (active pharmaceutical ingredients, APIs) included in nanosuspensions can exist in crystalline or amorphous forms. The produced liquid pre-dispersion can be converted into intermediate solid products, such as powder, by means of drying or into a semi-solid formulation,such as gel (Bartos et al, 2016;Hao et al, 2015;Lindfors et al, 2007;Rabinow, 2004).…”

Optimization of a combined wet milling process in order to produce poly(vinyl alcohol) stabilized nanosuspension

“…This study was performed using 2.5% PVA solution. 23 The ratio of the concentrated predispersion (2.0 g of Mel+18.0 g of PVA aqueous solution) and pearl amount was different: 1:0.5, 1:1, 1:2, and 1:4 (w/w). It can be established that the pearl amount and the milling time have a great effect of on the d (0.5) value ( Table 1 ).…”

“…In our earlier studies, we investigated the applicability of the combined wet milling technique, 20 – 23 and these preliminary studies showed that for the nanonization of Mel, PVA as a stabilizer agent and an increased milling time (>50 min) were required. The influence of milling time was also studied on the particle size distribution, crystallinity, and dissolution rate of Mel.…”