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

Csilla Bartos,Gábor Katona,Csaba Bartos,Orsolya Jójárt-Laczkovich,Piroska Szabó-Révész,Rita Ambrus

doi:10.3390/molecules21040507

Csilla Bartos, Gábor Katona + Show 4 more

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https://doi.org/10.3390/molecules21040507

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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 (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.

Highlights

One of the major current challenges of the pharmaceutical industry is related to strategies that improve the water solubility of drugs because over 40% of new drug candidates are water-insoluble compounds [1]
Further milling led to an increase in particle size, because MEL particles aggregated without the presence of polyvinyl alcohol (PVA)
The aqueous solubility of MEL (4.4 μg/mL, 25 ̋ C) increased due to the elevated temperature (40 μg/mL, 37 ̋ C), but it was not remarkable in our investigation, and 0.8 mg MEL could be dissolved in our dispersant medium of the presence 2 g of active agent

Summary

Introduction

One of the major current challenges of the pharmaceutical industry is related to strategies that improve the water solubility of drugs because over 40% of new drug candidates are water-insoluble compounds [1]. Water-soluble drug properties can impede the effective delivery of these drugs into humans, and affect their dissolution rate and subsequent absorption at the site of activity [2]. Soluble molecules have been successfully formulated by employing a variety of techniques to modify the physico-chemical and biopharmaceutical properties of drugs [3,4] such as:. Milling is a technique commonly applied to produce micro- or nanosized drug crystals in order to increase the dissolution rate and absorption, and the bioavailability of poorly-soluble materials. According to the Noyes-Whitney equation, the reduction of the particle sizes of drug crystals increases the specific surface area, which can improve the rate of dissolution of the drug [11]. There are many different well-known types of milling techniques with both advantages and disadvantages; dry and Molecules 2016, 21, 507; doi:10.3390/molecules21040507 www.mdpi.com/journal/molecules

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