Spray Cooling Process Factors and Quality Interactions During the Preparation of Microparticles Containing an Active Pharmaceutical Ingredient

Abstract

The current work studies the spray-cooling process factors and quality interactions during the production of microparticulated solid dispersions containing piroxicam, polyethylene glycol 4000, and poloxamer 407. The Box-Behnken factorial design was used to evaluate the influence of the temperature of the molten dispersion, the percentage of poloxamer 407 in the sample, and dispersion feed rate on the microparticles. The dependent variables studied by this design were particle size, flow properties, drug content, and solubility. Microparticle characterization was done through X-ray powder diffraction, thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and in vitro dissolution analysis. Statistical analysis showed that the factors studied in Box-Behnken factorial design significantly influenced (p < 0.05) the Carr index, the Hausner factor, and the solubility of these microparticles. The microparticles presented average diameter from 72 to 120 µm, moderate to excellent flowability, drug content between 77.5 to 99.2%, and an increase in solubility between 2.5- and 5.4-fold when compared to the solubility of the pure drug. In dissolution tests, more than 75.0% of the piroxicam present in the microparticles was released in just 2.5 minutes and the microparticles promoted a total release of the drug. In addition, microparticles increased both the release rate and the amount of drug released.

Keywords:

• Box-Benhken factorial design
• Piroxicam
• Spray congealing

Notes

Notes: X₁: coded value of the temperature of the molten dispersion; X₂: coded value of the percentage of poloxamer 407 in the sample; X₃: coded value of the dispersion feed rate.

Notes: Intersections, linear and quadratic coefficients, and correlation coefficients of polynomial fits for the dependent variables D ₅₀, α, CI, HF, DC, and S as functions of the factors. T: temperature of the molten dispersion; P_POL: percentage of poloxamer 407 in the sample; D_FR: dispersion feed rate. Fitted by surface response methodology.

^a Significant at p < 0.05.