Fabrication of Submicrometer-Sized Meloxicam Particles Using Femtosecond Laser Ablation in Gas and Liquid Environments

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.

A comparative study of femtosecond pulsed laser ablation of meloxicam in distilled water and in air

“…Our present work focuses on the femtosecond pulsed laser ablation of pressed meloxicam pastilles in distilled water (pulsed laser ablation in liquid, PLAL) and in air (pulsed laser ablation, PLA). This study is an extension of our previous investigation 35 , and it complements our studies on nanosecond pulsed laser ablation of meloxicam in liquid 36,37 , in air 38 and ibuprofen in vacuum 39 . The aim was to investigate the ablation process with laser parameters (femtosecond pulses with kHz repetition rate) that are orders of magnitude different from those in our previous works, and to see how suitable it is for pharmaceutical applications.…”

Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐alt‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study

“…The fluorescence of meloxicam powder in the CH─ stretching region (2700–3200 cm −1 ) is so high that it could not be used for imaging. However, lower CARS shift regions showed a good signal, and a characteristic CARS spectrum [ 22 ] was obtained between 1400 and 1800 cm −1 ( Figure A). Furthermore, in the CARS spectrum area, both PVP and PMVE–MA showed no clear Raman peaks, making imaging our MN formulation possible.…”

“…[ 21 ] As a nondestructive method, CARS microscopy facilitates real‐time in situ imaging, thereby proving indispensable for examining the crystal structure of pharmaceuticals like meloxicam encapsulated within MN patches. [ 22 ]…”

“…[21] As a nondestructive method, CARS microscopy facilitates real-time in situ imaging, thereby proving indispensable for examining the crystal structure of pharmaceuticals like meloxicam encapsulated within MN patches. [22] Upon formulating meloxicam in a double-layered MN patch and assessing its critical attributes in terms of morphology, drug loading and status, and structural integrity, we proceeded to investigate the in vitro release and skin permeability, as well as evaluated the bioavailability and efficacy through in vivo studies. Moreover, we showcased the short-term stability of the formulation, providing a comprehensive assessment of its performance and potential for further development.…”

Emerging applications of femtosecond laser fabrication in neurobiological research

“…It is reported that nanoparticles smaller than 100 nm are more likely to cross the BBB (Nance et al, 2022). Eszter et al reduced the particle size down to submicron scale (50 nm) by laser ablation strategy, and applied them to transnasal drug delivery (Nagy et al, 2021). Furthermore, Ajay et al reduced the particle size to 20-25 nm, and successfully carried three drugs for HIV-1 (Figure 1C) (Singh et al, 2020).…”