Towards characterization and identification of solid state pharmaceutical mixtures through second harmonic generation.
In this paper, we report improvements to a previously developed method based on optical nonlinearity for characterizing polymorphism and concentration of pharmaceuticals in powdered and tablet form. An apparatus that measures the nonlinear optical response of a sample through second harmonic generation (SHG) is described. The response of several enalapril maleate-polyvinylpyrrolidone (PVP) tablets was measured, the results of which were used to determine the concentration of the drug. The current limit of detection of the apparatus was found to be approximately 1%-2%. Ranitidine hydrochloride (RN) polymorph forms I and II were also characterized using SHG. It was found that pure samples of forms I and II could be clearly and rapidly distinguished. Mixtures consisting of 50% form I and 50% form II were also distinguishable from the respective pure forms. An investigation was performed into the size dependence of the SHG response for crystalline lactose. It was found that the SHG response was a slowly decreasing monotonic function of particle size. Additional investigation into the angular dependence of the scattered SHG light was also undertaken for crystalline lactose. This new technique based on optical nonlinearity offers promise for application in monitoring of pharmaceutical manufacturing processes.
Physics Department, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Chris B
CB
Rawle
Chris J
CJ
Lee
Clare J
CJ
Strachan
Keith
K
Payne
Peter J
PJ
Manson
Thomas
T
Rades
D001331:Automation; D003201:Computers; D003460:Crystallization; D004656:Enalapril / Q000032:analysis / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D007834:Lasers; D055095:Optics and Photonics; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D011208:Powders; D011899:Ranitidine / Q000032:analysis / Q000737:chemistry; D013053:Spectrophotometry / Q000295:instrumentation* / Q000379:methods*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation
D004364:Pharmaceutical Preparations; D011208:Powders; D013607:Tablets; D004656:Enalapril; D011899:Ranitidine; D011205:Povidone; D007785:Lactose