Functionalization of inhalable particles by fluidized bed processing.

摘要

This work focused initially on the size reduction of naproxen sodium to less than 5 microm for inhalation applications. The second objective was the adhesion of naproxen sodium particles to micronized lactose particles with an average size below 5 microm. Both processes were executed in a fluid bed processing unit at high vacuum pressure.;The desired particles were obtained by precipitation in a fluid bed processing unit at a pressure at the nozzle of 551.43 kPa from a naproxen sodium solution flowing at 1.0 ml/s for 30 seconds through a nozzle. This solution contained 30% (v/v) ethanol, 20% naproxen sodium by weight at a temperature of 313.15 K. The solution entered the fluid bed processing unit operating at high vacuum pressure which maintains the fluidization with a flow rate of air at 5 m/s for 10 minutes. These conditions ensured a crystallization of naproxen sodium smaller than 5 microm.;The functionalization of the particles of the micronized lactose particles by naproxen sodium were performed in the same fluid bed processing unit under the same conditions used for the crystallization process of naproxen sodium.;The composition of the particles functionalized was determined using Energy Dispersive X-Ray microanalysis, which identified the sodium atoms of the crystallized naproxen sodium.;The crystalline structure of micronized lactose, naproxen sodium, naproxen sodium crystallized, and particles functionalized was determined using X-Ray Diffraction with Kalpha 1.54056 A° with a range angle of 7° to 74° showing a small deviation between micronized lactose and naproxen sodium crystallized. It is shown that a change in the crystal arrangements between naproxen sodium and naproxen sodium crystallized occurred after the crystallization.;The average particles size obtained for the micronized lactose was 2.349 microm, for the naproxen sodium crystallized is 2.280 microm, and for the particle functionalized is 4.040 microm. The images of the particles obtained with a Scanning Electron Microscope were analyzed with the Scandium Software for the determination of particle sizes, and morphology. The accumulation distribution of the micronized lactose particles and naproxen sodium crystallized with less than 5 microm was 90%, and 80% for the particles functionalized.;The micronized lactose, naproxen sodium, naproxen sodium crystallized, and particles functionalized were characterized using Fourier Transform Infrared Spectroscopy. The wavenumber region studied for the particles functionalized was from 960--1160 cm-1. However, the wavenumber range for the micronized lactose, naproxen sodium, and naproxen sodium crystallized was 780--1680 cm-1.;The particles functionalized resulted by adhesion of naproxen sodium crystallized over micronized lactose were due to Van der Waals, intermolecular, electrostatic, and magnetic forces. These particles functionalized can be used as inhalation products since they complied with the requirement of a particle size less than 10 microm.