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

Authors Bartos C, Jójárt-Laczkovich O, Katona G, Budai-Szűcs M, Ambrus R, Bocsik A, Gróf I, Deli MA, Szabó-Révész P

Received 16 December 2017

Accepted for publication 20 March 2018

Published 31 May 2018 Volume 2018:12 Pages 1567—1580


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng

Csaba Bartos,1 Orsolya Jójárt-Laczkovich,1 Gábor Katona,1 Mária Budai-Szűcs,1 Rita Ambrus,1 Alexandra Bocsik,2 Ilona Gróf,2 Mária Anna Deli,2 Piroska Szabó-Révész1

1Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary; 2Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary

Purpose: The article reports a wet milling process, where the planetary ball mill was combined with pearl milling technology to reach nanosize range of meloxicam (Mel; 100–500 nm). The main purpose was to increase the dissolution rate and extent of a poorly water-soluble Mel as nonsteroidal anti-inflammatory drug as well as to study its permeability across cultured intestinal epithelial cell layers.
Methods: Viscosity of milled dispersion and particle size distribution and zeta potential of Mel were investigated and differential scanning calorimeter and X-ray powder diffractometer were used to analyse the structure of the suspended Mel. Finally in vitro dissolution test and in vitro cell culture studies were made.
Results: It was found that the ratio of predispersion and pearls 1:1 (w/w) resulted in the most effective grinding system (200-fold particle size reduction in one step) with optimized process parameters, 437 rpm and 43 min. Nanosuspension (1% Mel and 0.5% poly[vinyl alcohol]) as an intermediate product showed a stable system with 2 weeks of holding time. This optimized nanosuspension enhanced the penetration of Mel across cultured intestinal epithelial cell layers without toxic effects.
Conclusion: The dissolution rate of Mel from the poly(vinyl alcohol) stabilized nanosuspension justified its applicability in the design of innovative per oral dosage form (capsule) in order to ensure/give a rapid analgesia.

Keywords: nanonization, meloxicam, milled dispersion, milling efficiency, zeta potential, intermediate product

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