Quantitative measurements of concentration and solubility using Raman spectroscopy

• US 20050228594A1
• Filed: 04/11/2005
• Published: 10/13/2005
• Est. Priority Date: 04/12/2004
• Status: Active Grant

• Current Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: TransForm Pharmaceuticals, Inc. (Johnson & Johnson)
• Inventors: Pryce-Lewis, Wendy, Shimizu, Kentaro, Sun, Evie
• Granted Patent: US 7,521,254 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

The present invention provides methods which allows for the determination of concentration or solubility in a multi-component system using Raman spectroscopy. The present invention circumvents the necessity of constructing a calibration curve in order to analytically determine the concentration/solubility of a solute in a homogeneous liquid or a homogeneous solid. Methods of determining the saturation concentration of a solute in a polymer matrix or a polymer matrix film are also provided.

Claims

1. A method of determining the saturation concentration of a solute in a polymer matrix or a polymer matrix film, comprising:

(a) obtaining a calibration curve;

(b) preparing samples with high solute concentration;

(c) allowing said samples to reach equilibrium;

(d) finding a crystal within said polymer matrix or polymer matrix film;

(e) scanning a laser beam off the face of the crystal; and

(f) determining C_sat at the crystal interface.

2. The method of claim 1, wherein:

(a) said calibration curve in step (a) comprises the intensity between the solute signal and the polymer matrix or polymer matrix film for each formulation;

(b) said calibration curve in step (a) comprises the normalized intensity between the solute signal and the polymer matrix or polymer matrix film for each formulation;

(c) said calibration curve in step (a) is constructed using several low solute level samples;

(d) said samples in step (b) are prepared with high solute concentration and a high driving force to nucleate;

(e) said samples in step (b) are prepared with seed crystals;

(f) said crystal in step (d) is found using an in-line vision station;

(g) said crystal in step (d) is found using a CCD camera;

(h) said laser beam in step (e) is scanned in increments;

(i) said laser beam in step (e) is scanned in increments of at least about 1.0 micrometer;

(j) said laser beam in step (e) is scanned in increments of about 10.0 micrometers;

(k) C_sat is determined by analyzing a Raman signal at the interface;

or

(l) C_sat is determined by analyzing a normalized Raman signal at the interface.