Polymorph characterization and control

Author

Michael J. Donahue, University of Rhode Island

Date of Award

2007

Degree Type

Dissertation

First Advisor

Christopher W. Brown

Abstract

Sustainability in the pharmaceutical industry will require the ability to monitor, and ultimately control production processes in real time. One area of particular concern is that of polymorphism, where there is a change of crystalline state for a compound, resulting in varied physiological properties. For this work we have looked at three such processes. First, an investigation of the ability to monitor polymorphic transitions in a pharmaceutical product, glycine, has been developed though optical spectroscopy. Second, the ability to induce nucleation of a particular polymorph via a novel method of acoustic levitation has been explored. Lastly, a method of characterization of polymorphic variability was explored with an infrared microscope. The first topic investigates a method to monitor the manufacture of a specific crystalline polymorph. It has been reported that optical methods offer promise for real-time monitoring of polymorphism, with the ability to distinguish amongst crystalline states. Optical spectroscopy offers a rapid, potentially in-line method for the evaluation of polymorphic purity. The development of one such system has been explored via the careful analysis for mixtures of the polymorphs of the amino acid glycine. The second part of the intended research is aimed at the development of a novel means of nucleating a particular crystalline state via ultrasonic interference. Saturated solutions of the amino acid glycine were placed on piezoelectric transducers to examine nucleation tendencies while the sample was subject to acoustic vibration. As a result, it has been observed that the γ-polymorph of glycine can be produced in this novel fashion. Finally, in the development of the mixing schemes used to explore the spectral variations, a method of gathering spectra with the microscope was developed. Specifically, microsampling techniques whereby the mixing was done optically rather than physically allowed for the collection of mixture data with the smallest amount of sample. Simply put, wafers of each polymorph were placed side by side and moved incrementally across the field of view for data collection. Thus investigations as to the makeup of suspected polymorphic contamination can be carried out quite simply and without the creation of simulated data.

Recommended Citation

Donahue, Michael J., "Polymorph characterization and control" (2007). Open Access Dissertations. Paper 2163.
https://digitalcommons.uri.edu/oa_diss/2163