The Effect of an Optimized Wet Milling Technology on the Crystallinity, Morphology and Dissolution Properties of Micro- and Nanonized Meloxicam.
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 (D50 = 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.
Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. bartoscsilla@pharm.u-szeged.hu.
Csilla
C
Bartos
Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. revesz@pharm.u-szeged.hu.
Piroska
P
Szabó-Révész
Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. bartoscsaba@pharm.u-szeged.hu.
Csaba
C
Bartos
Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. katona@pharm.u-szeged.hu.|Gedeon Richter Plc., Gyömrői út 19-21, H-1103 Budapest, Hungary. katona@pharm.u-szeged.hu.
Gábor
G
Katona
Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. laczkovo@pharm.u-szeged.hu.
Orsolya
O
Jójárt-Laczkovich
Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. arita@pharm.u-szeged.hu.
Rita
R
Ambrus
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D000077239:Meloxicam; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013843:Thiazines / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam
crystallinity; in vitro dissolution; micronization; nanonization; physical structure; wet milling