Method for monitoring particle size
View Patent ↗The present invention provides methods for the use of visible and/or near-infrared spectroscopic methodology to monitor and control processes for the generation of particles, including processes that provide for a reduction in particle size and processes that result in an increase in particle size. One embodiment of the present invention employs visible and/or near-infrared diffuse reflectance spectroscopy to monitor particle size. The present invention is particularly useful for monitoring particle size of optically dense samples and is further useful for monitoring the endpoint of particle generation processes. In contrast to methods known in the art, the present invention is especially useful for on-line monitoring of particle size.
1. A method for monitoring the change in size of particles in a solvent during a process to generate such particles that comprises:
(a) obtaining a first near-infrared diffuse reflectance spectra in a diffuse reflectance backscattered configuration of the particles in the solvent at an initial time point;
(b) obtaining a second near-infrared diffuse reflectance spectra in a diffuse reflectance backscattered configuration of the particles in the solvent at a later time point;
(c) comparing the first near-infrared diffuse reflectance spectra to the second near-infrared diffuse reflectance spectra to monitor the change in size of the particles, wherein the monitoring of the change in size of the particles is used to control the process to generate such particles.
2. The method of claim 1 for monitoring the change in size of particles of a pharmaceutical compound in a solvent during a process to generate such particles.
3. The method of claim 1 wherein the near infrared spectroscopic data are collected at a wavelength of about 1460 nm.
4. The method of claim 1 wherein the solvent comprises water.
5. The method of claim 1 wherein the monitoring of the change in size of particles is employed for on-line or continuous monitoring of particle size in a process for particle generation.
6. The method of claim 1 wherein the size of the particles changes within the range of 100 microns to 200 nm.
7. A method for monitoring the change in size of particles in a solvent during a process to generate such particles that comprises:
(a) obtaining near-infrared diffuse reflectance spectra in a diffuse reflectance backscattered configuration for a plurality of reference samples of particles in the solvent wherein the particles in each reference sample possess a known size;
(b) obtaining near-infrared diffuse reflectance spectra in a diffuse reflectance backscattered configuration of the particles in the solvent during the process to generate the particles;
(c) comparing the spectra from the process to generate the particles to the spectra for the plurality of reference samples;
(d) identifying which of the spectra for the plurality of reference samples most closely matches the spectra from the process to generate the particles, thereby correlating the known size of the particles in the reference sample to the size of the particles resulting from the process to generate the particles, wherein correlating the known size of the particles in the reference sample to the size of the particles resulting from the process to generate the particle is used to control the process to generate such particles;
(e) repeating steps (a)-(d) until the particles resulting from the process to generate the particles have reached the desired size.
8. The method of claim 7 wherein the near infrared spectroscopic data are collected at a wavelength of about 1460 nm.
9. The method of claim 7 wherein the solvent comprises water.
10. The method of claim 7 wherein the monitoring of the change in size of particles is employed for on-line or continuous monitoring of particle size in a process for particle generation.
11. The method of claim 7 wherein the size of the particles changes within the range of 100 microns to 200 nm.
12. A method for determining when the size of particles in a solvent has reached a steady state during a process to generate such particles that comprises:
(a) obtaining a first near-infrared diffuse reflectance spectra in a diffuse reflectance backscattered configuration of the particles in the solvent at an initial time point;
(b) obtaining a second near-infrared diffuse reflectance spectra in a diffuse reflectance backscattered configuration of the particles in the solvent at a later time point;
(c) comparing the first near-infrared diffuse reflectance spectra to the second near-infrared diffuse reflectance spectra; and
(d) repeating steps (a)-(c) until there are no significant differences between the first near-infrared diffuse reflectance spectra and the second near-infrared diffuse reflectance spectra, wherein the foregoing steps are used to control the process to generate such particles.
13. The method of claim 12 for determining when the size of particles of a pharmaceutical compound in a solvent has reached a steady state during a process to generate such particles.
14. The method of claim 12 wherein the near infrared spectroscopic data are collected at a wavelength of about 1460 nm.
15. The method of claim 12 wherein the solvent comprises water.
16. The method of claim 12 wherein the monitoring of the change in size of particles is employed for on-line or continuous monitoring of particle size in a process for particle generation.
17. The method of claim 12 wherein the size of the particles changes within the range of 100 microns to 200 nm.