Quantification method of impurities in lactide

Abstract

A method for quantification of the amount of impurities in lactide. The method is characterized in that the quantification of the impurities is based on measurements performed on absorptions in the near Infra-Red region of the electromagnetic spectrum. With this method, small amounts of impurities like water, free-acid species or both can be determined online in a reaction mixture of lactide in a relatively simple manner. This allows a simple online monitoring of the production process of lactide.

Claims

1. Method for quantification of impurities in lactide, comprising obtaining absorption spectra of the lactide in a near Infra-Red region of the electromagnetic spectrum ranging from 12000 cm.sup.1 to 4000 cm.sup.1 so as to capture second and higher overtones of the lactide and of the impurities, and quantifying an amount of the impurities in the lactide by performing measurements on the obtained absorption spectra, wherein the lactide is a cyclic dimer of lactic acid, and wherein the impurities are impurities bearing hydroxyl and/or carboxylic acid groups.

2. Method according to claim 1, wherein the impurities comprise water.

3. Method according to claim 1, wherein the impurities comprise free acid species.

4. Method according to claim 1, wherein the amount of impurities is quantified in lactide being in a liquid aggregate phase.

5. Method according to claim 1, wherein the amount of impurities is quantified in lactide being in a solid aggregate phase.

6. Method according to claim 1, wherein the amount of impurities is quantified during a lactide production process based on the measurements performed on the absorption spectra that are obtained in lactide prepared by depolymerization of oligomers of lactic acid.

7. Method according to claim 6, wherein the lactide production process is a batch process.

8. Method according to claim 6, wherein the lactide production process is a continuous process.

9. Method according to claim 8, wherein the amount of impurities in the lactide is quantified simultaneously at different stages of the continuous lactide production process.

10. Method according to claim 9, wherein the quantification of the amounts of the impurities is used to control production parameters, in order to adjust the continuous lactide production process.

Description

BRIEF DESCRIPTION OF THE INVENTION

(1) The present invention is described in more detail and elucidated by different examples and a drawing, in which

(2) FIG. 1 shows an overlay of several nIR spectra of lactide with different amounts of free acid species and water,

(3) FIG. 2 shows a cross validation plot of measured and calculated data of free acid species concentrations in lactide, and

(4) FIG. 3 shows a cross validation plot of measured and calculated data of water concentrations in lactide.

DETAILED DESCRIPTION OF THE INVENTION

(5) In an experiment, approximately 550 grams of lactide (freshly prepared with an extreme low amount of free acid species and water) was melted under a nitrogen blanket in a round bottom flask of 500 ml with 4 necks by a heating jacket. The temperature of the lactide inside the round bottom flask was controlled by a special temperature controller. A nIR probe was inserted in the lactide liquid aggregate phase and the data acquisition was started. Every 17 seconds a spectrum was acquired. The amounts of the impurities were determined by titration, more particularly with a Karl Fischer titration method for the water content and a titration with Potassium Methanoate to determine the amount of free acid species. The titration was performed using a Titrino 736 apparatus with a 730 autosampler. The moment of sampling was used to connect the results with a single nIR spectrum which was used to develop a corresponding measuring model.

(6) In FIG. 1 an overlay of several nIR spectra is shown, in which the absorption A is depicted as a function of the wave number W (in cm.sup.1). In more detail, this Figure shows a series of nIR spectra of the measured lactide in liquid state in which determined amounts of water and free acid species are present. The spectra of the lactide in liquid aggregate state were recorded in transmission mode over the range between approximately 12000 and 4000 cm.sup.1. The water content and free acid species content of the lactide samples of which the spectra are shown ranged between 10-381 mmol per kg lactide and 0.0113-0.695% (w/w), respectively. The measurements were performed with a Bruker MPA Matrix F duplex NIR spectrometer. Peaks of particular interest for the quantification method according to the present invention are located in the spectral range between 7300 and 4500 cm.sup.1. This is the area in which vibrations of the molecular OH-bonds in the different molecules of interest show overtones.

(7) FIG. 2 shows a so-called cross-validation curve of measured amounts of free acid (in mmol/kg) in the freshly prepared lactide. In this Figure, the modeled concentration (C.sub.m) is plotted as a function of the experimentally determined concentration (C.sub.exp). In order to determine these curves, small amounts of lactic acid were added to the mixture during a period of time. At a number of time slots, a measuring sample was taken from the flask, which sample was frozen and the amount of free acid was determined by titration. At the moment of sample taking, a nIR spectrum was recorded over the indicated area. Based on the titration results, the recorded spectra and the software used, the plotted best-fit curves could be obtained for both the calibration curve and the cross validation curve.

(8) From FIG. 2, it can be concluded that with the used nIR method it is possible to determine the amount of free acid species in pure lactide within a range of 6 to 600 mmol/kg with a confidence interval of 4 mmol/kg (SECV, this is the error for the whole model, at the lower part of the calibration line this error becomes 1 mmol/kg). In these early experiments, it was not possible to test the system at lower free acid numbers because the material had to be melted and small amounts of air can enter the set-up resulting in adsorption of water which is then (partly) converted to free acid. In later experiments, it was confirmed that free acid species amounts as low as 2 mmol/kg lactide could be measured with nIR with a confidence level RMSECV of 0.33 mmol/kg (cross validation plot not shown).

(9) FIG. 3 shows a cross-validation curve of measured amounts of water (in %.w/w) in the freshly prepared lactide. In this Figure, the modeled concentration (C.sub.m) is plotted as a function of the experimentally determined concentration (C.sub.exp). In order to determine these curves, the above-mentioned sample was allowed to absorb water during a period of time. At a number of time slots, a measuring sample was taken from the flask, which sample was frozen and the amount of water was determined by titration. As the moment of sample taking, a nIR spectrum was recorded over the indicated area. Based on the titration results, the recorded spectra and the software used, the plotted best-fit curves could be obtained for both the calibration curve and the cross validation curve.

(10) From FIG. 3, it can be concluded that with the used nIR method it is possible to determine the amount of water in pure lactide within a range of 0.006 to 0.2% (w/w) with a confidence interval of 0.01% (w/w). The accuracy of the determination of water is less good compared with the accuracy of the amount of free acid species (correlation coefficient 0.9681 versus 0.9999). This is partly due to the fact that the used reference method has a larger confidence interval.

(11) The Relative Standard Deviation (RSD) of the free acid titration is less than 2.5%. For the water titration the RSD is much higher. The samples are very sensitive to moisture from the air. The lower precision of the water determination is most likely caused by the stability of the sample and the time it takes between sampling and analysing (a few minutes). The precision of the NIR method will be equal or less compared to the precision of the used reference method.

(12) In addition to the above mentioned experimental results, it has also been shown that both mentioned impurities (water and free acid) can be measured and quantified simultaneously in lactide samples.

(13) In summary, it has been shown that, with the presently invented lactide quantification method, small amounts of impurities like water and free-acid can be determined online in a reaction mixture of lactide in a relatively simple manner. This allows a simple online monitoring of the production process of lactide.

(14) While the invention has been illustrated and described in detail in the foregoing description, such description is to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments and experiments. Variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the disclosure and the appended claims.

(15) In the claims, the word comprising does not exclude other elements or steps, and the indefinite article a or an does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.