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

Abstract We studied the application of pulsed laser ablation (PLA) for particle size reduction in non-steroidal anti-inflammatory drugs (NSAIDs). Grinding of the poorly water-soluble NSAID crystallites can considerably increase their solubility and bioavailability, thereby the necessary doses can be reduced significantly. We used tablets of ibuprofen, niflumic acid and meloxicam as targets. Nanosecond laser pulses were applied at various wavelengths (KrF excimer laser, λ = 248 nm, FWHM = 18 ns and Nd:YAG laser, λ1 = 532 nm/λ2 = 1064 nm, FWHM = 6 ns) and at various fluences. FTIR and Raman spectra showed that the chemical compositions of the drugs had not changed during ablation at 532 nm and 1064 nm laser wavelengths. The size distribution of the ablated products was established using two types of particle size analyzers (SMPS and OPC) having complementary measuring ranges. The mean size of the drug crystallites decreased from the initial 30–80 µm to the submicron to nanometer range. For a better understanding of the ablation mechanism we made several investigations (SEM, Ellipsometry, Fast photography) and some model calculations. We have established that PLA offers a chemical-free and simple method for the size reduction of poorly water-soluble drugs and a possible new way for pharmaceutical drug preformulation for nasal administration.

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

Nanomaterials ◽

10.3390/nano11040996 ◽

2021 ◽

Vol 11 (4) ◽

pp. 996

Author(s):

Eszter Nagy ◽

Attila Andrásik ◽

Tamás Smausz ◽

Tibor Ajtai ◽

Fruzsina Kun-Szabó ◽

...

Keyword(s):

Particle Size ◽

Laser Ablation ◽

Water Solubility ◽

Chemical Change ◽

Pulsed Laser ◽

Pulsed Laser Ablation ◽

Water Soluble ◽

Size Reduction ◽

Distilled Water ◽

Particle Size Reduction

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.

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Preparation of ZnO Nanoparticles by 1064/532nm Laser Ablation and Studying the Effect of the Ablation Wavelength

Materials Science Forum ◽

10.4028/www.scientific.net/msf.1021.171 ◽

2021 ◽

Vol 1021 ◽

pp. 171-180

Author(s):

Munaf S. Majeed ◽

Rabea Q. Nafil ◽

Marwa F. Abdul Jabbar ◽

Kadhim H. Suffer

Keyword(s):

Zinc Oxide ◽

Laser Ablation ◽

Pure Water ◽

Pulsed Laser ◽

Pulsed Laser Ablation ◽

Ultra Pure Water ◽

Hexagonal Shape ◽

532 Nm ◽

Laser Ablation Technique

We prepared Zinc oxide nanomaterial employing PLA (pulsed laser ablation) technique. A pure Zn target was immersed in ultra-pure water (UPW) and it was subjected to several pulses (1st. and 2nd. harmonic) of the pumping Nd: YAG laser. The influence of changing laser’s wavelength (1064, 532) nm on the characterization of the produced nanoparticles was studied. The results obtained from studying the structure, topography, and morphology of the product showed that the particles have a hexagonal shape. Also, changing the wavelength of the laser from 532nm to 1064nm leads to size reduction and density increasing of the nanoparticles.

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Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process

Pharmaceutics ◽

10.3390/pharmaceutics13122061 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2061

Author(s):

Jeong-Soo Kim ◽

Heejun Park ◽

Eun-Sol Ha ◽

Kyu-Tae Kang ◽

Min-Soo Kim ◽

...

Keyword(s):

Particle Size ◽

Surface Layer ◽

Dissolution Rate ◽

Spray Drying ◽

Supercritical Fluid ◽

Water Soluble ◽

Size Reduction ◽

Particle Size Reduction ◽

Surface Active ◽

Poorly Water Soluble

In this study, supercritical fluid-assisted spray-drying (SA-SD) was applied to achieve the micronization of fenofibrate particles possessing surface-active additives, such as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose mono palmitate (Sucroester 15), and polyoxyethylene 52 stearate (Myrj 52), to improve the pharmacokinetic and pharmacodynamic properties of fenofibrate. For comparison, the same formulation was prepared using a spray-drying (SD) process, and then both methods were compared. The SA-SD process resulted in a significantly smaller mean particle size (approximately 2 μm) compared to that of unprocessed fenofibrate (approximately 20 μm) and SD-processed particles (approximately 40 μm). There was no significant difference in the effect on the particle size reduction among the selected surface-active additives. The microcomposite particles prepared with surface-active additives using SA-SD exhibited remarkable enhancement in their dissolution rate due to the synergistic effect of comparably moderate wettability improvement and significant particle size reduction. In contrast, the SD samples with the surface-active additives exhibited a decrease in dissolution rate compared to that of the unprocessed fenofibrate due to the absence of particle size reduction, although wettability was greatly improved. The results of zeta potential and XPS analyses indicated that the surface-active additive coverage on the surface layer of the SD-processed particles with a better wettability was higher than that of the SA-SD-processed composite particles. Additionally, after rapid depletion of hydrophilic additives that were excessively distributed on the surfaces of SD-processed particles, the creation of a surface layer rich in poorly water-soluble fenofibrate resulted in a decrease in the dissolution rate. In contrast, the surface-active molecules were dispersed homogeneously throughout the particle matrix in the SA-SD-processed microparticles. Furthermore, improved pharmacokinetic and pharmacodynamic characteristics were observed for the SA-SD-processed fenofibrate microparticles compared to those for the SD-processed fenofibrate particles. Therefore, the SA-SD process incorporating surface-active additives can efficiently micronize poorly water-soluble drugs and optimize their physicochemical and biopharmaceutical characteristics.

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Preparation and characterization of N-benzyl-N,O-succinyl chitosan polymeric micelles for solubilization of poorly soluble non-steroidal anti-inflammatory drugs

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v16i10.6 ◽

2017 ◽

Vol 16 (10) ◽

pp. 2349-2357

Author(s):

Thisirak Woraphatphadung ◽

Warayuth Sajomsang ◽

Theerasak Rojanarata ◽

Prasert Akkaramongkolporn ◽

Tanasait Ngawhirunpat ◽

...

Keyword(s):

Particle Size ◽

Surface Charge ◽

Polymeric Micelles ◽

Rank Order ◽

Drug Loading ◽

Polymer Concentration ◽

Water Soluble ◽

Loading Efficiency ◽

Inflammatory Drugs ◽

Anti Inflammatory

Purpose: To investigate the solubilization of poorly water-soluble non-steroidal anti-inflammatory drugs (NSAIDs) in N-benzyl-N,O-succinyl chitosan (BSCS) polymeric micellesMethods: BSCS was synthesized by reductive amination and succinylation, respectively. NSAIDs; meloxicam (MX), piroxicam (PRX), ketoprofen (KP) and indomethacin (IND) were entrapped in the hydrophobic inner cores by evaporation method. The effects of drug structure on loading efficiency, particle size and surface charge of micelles were investigated.Results: The critical micelle concentration of BSCS micelles was 0.0385 mg/mL and cytotoxicity on Caco-2 cells depends on the polymer concentration (IC50 = 3.23 ± 0.08 mg/mL). BSCS micelles were able to entrap MX, PRX, KP and IND and also improve the solubility of drugs. Drug loading efficiency was highly dependent on the drug molecules. The drug loading capacity of these BSCS micelles was in the following rank order: KP (282.9 μg/mg) > PRX (200.8 μg/mg) > MX (73.7 μg/mg) > IND (41.2 μg/mg). The highest loading efficiency was observed in KP-loaded BSCS micelles due to the attractive force between phenyl groups of KP and benzyl groups of the polymer. Particle size and surface charge were in the range of 312 - 433 nm and -38 to -41 mV, respectively.Conclusion: BSCS copolymer presents desirable attributes for enhancing the solubility of hydrophobic drugs. Moreover, BSCS polymeric micelles might be beneficial carrier in a drug delivery system.Keywords: BSCS, polymeric micelles, solubilization, non-steroidal anti-inflammatory drugs

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Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity

Malaria Research and Treatment ◽

10.1155/2013/769234 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Hongxing Wang ◽

Qigui Li ◽

Sean Reyes ◽

Jing Zhang ◽

Lisa Xie ◽

...

Keyword(s):

Particle Size ◽

Solid Dispersion ◽

Antimalarial Activity ◽

Fold Increase ◽

Water Soluble ◽

Size Reduction ◽

Particle Size Reduction ◽

Physical Form ◽

Poorly Water Soluble ◽

Nanoparticle Formulation

Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L-α-phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

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