Abstract

In pharmaceutical development, more and more drugs are classified as poorly water-soluble or insoluble. Particle size reduction is a common way to fight this trend by improving dissolution rate, transport characteristics and bioavailability. Pulsed laser ablation is a ground-breaking technique of drug particle generation in the nano- and micrometer size range. Meloxicam, a commonly used nonsteroidal anti-inflammatory drug with poor water solubility, was chosen as the model drug. The pastille pressed meloxicam targets were irradiated by a Ti:sapphire laser (τ = 135 fs, λc = 800 nm) in air and in distilled water. Fourier transform infrared and Raman spectroscopies were used for chemical characterization and scanning electron microscopy to determine morphology and size. Additional particle size studies were performed using a scanning mobility particle sizer. Our experiments demonstrated that significant particle size reduction can be achieved with laser ablation both in air and in distilled water without any chemical change of meloxicam. The size of the ablated particles (~50 nm to a few microns) is approximately at least one-tenth of the size (~10–50 micron) of commercially available meloxicam crystals. Furthermore, nanoaggregate formation was described during pulsed laser ablation in air, which was scarcely studied for drug/organic molecules before.

Highlights

  • Laser ablation is a widely used and versatile technique, especially in material processing

  • Whereas previous research mainly focused on metals [1,2,3,4,5] and metal alloys [6,7,8], in the past decade more and more studies have been published on particle generation by the laser ablation of organic materials too [9,10,11,12,13]

  • Our aim is to compare the ablation of a pure meloxicam target with femtosecond laser pulses in air and in distilled water, referred to as pulsed laser ablation (PLA) and pulsed laser ablation in liquid (PLAL), respectively, in this paper

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Summary

Introduction

Laser ablation is a widely used and versatile technique, especially in material processing. It can be applied to produce high-precision surface structures as well as submicrometersized particles from various materials in vacuum, gas or liquid. Whereas previous research mainly focused on metals [1,2,3,4,5] and metal alloys [6,7,8], in the past decade more and more studies have been published on particle generation by the laser ablation of organic materials too [9,10,11,12,13]. Particle size reduction (and thereby improvement in the surface to volume ratio) is a possible way to enhance the dissolution rate, transport characteristics and bioavailability of these drugs [15,16]. Size reduction can be achieved by different approaches [17,18], such as forming solid dispersions [19], grinding [20], wet milling [21], cavitation [22], and laser ablation [11,12,13,23,24,25,26,27,28,29]

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