Production of meloxicam suspension using pulsed laser ablation in liquid (PLAL) technique

Abstract

Production of organic particles in the micrometer/nanometer range can find applications in a wide range of areas, however for a number of materials it is not a straightforward task. In the present work pulsed laser ablation in liquid environment (PLAL) of meloxicam was studied aiming the production of near micrometer sized particles of this pharmaceutical ingredient. Targets pressed from crystalline meloxicam powder were placed in distilled water and irradiated with a focused beam of a frequency doubled (532 nm) nanosecond Nd:YAG laser at 4.2-9.4 J/cm 2 fluence. Morphological investigation showed that the produced suspension contained particles in the ∼100 nm to 10 µm size range, with 1.0-2.0 µm on average, which is about 10 times smaller than the size of the initial material. FTIR spectroscopic investigations demonstrated that the chemical composition was preserved, while XRD and calorimetric measurements indicated partial amorphization of meloxicam during the process. The overall results suggest that the particles are mostly produced by the fragmentation of the pressed target by the recoil forces of the ablating laser pulse. Long period sedimentation tests of the suspension combined with UV-Vis spectroscopic analysis showed that by the method of PLAL a greater fraction of the poorly water soluble meloxicam could be dispersed and dissolved in water in a pharmaceutically preferred formation than by simple dissolution of it.

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

“…The laminar, block-like and needle-shaped particles can be fractures of the pressed tablet, which preserved their solid state and retained the crystal structure ( Figure 7 ). The formation mechanism may be similar to that in a previously published experiment investigating nanosecond ablation in liquid [ 24 ]. In the current experiment, femtosecond laser irradiation induced fast material decomposition in a thin surface layer of the target, and the explosive expansion of the plasma plume that was created resulted in the formation of a shock wave.…”

“…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 ]. Laser ablation as a simple, rapid, easily adjustable and chemical-free method has received considerable attention in drug preformulation.…”

Application of pulsed laser ablation (PLA) for the size reduction of non-steroidal anti-inflammatory drugs (NSAIDs)

“…12) where submicron sized particle ejection occurs at nanosecond and few microsecond time scales. Larger, micron-sized and irregularly shaped particles are ejected in the microsecond scale [16][17][18][19] . The above observations apply mainly to homogeneous bulk materials.…”

“…It has already been shown that PLA/PLD is suitable for the size reduction of pharmaceutical particles without causing any chemical decomposition. In recent years, researchers have also started to use lasers for particle size reduction in drugs in liquid environment (PLAL) 18 – 23 .…”

“…any chemical decomposition. In recent years, researchers have also started to use lasers for particle size reduction in drugs in liquid environment (PLAL) [18][19][20][21][22][23] .…”