Towards characterization and identification of solid state pharmaceutical mixtures through second harmonic...

Area of Science:

• Analytical Chemistry
• Materials Science
• Pharmaceutical Science

Background:

• Pharmaceutical quality control requires accurate methods for characterizing drug concentration and polymorphism.
• Existing methods may be time-consuming or lack sensitivity for certain analyses.
• Optical nonlinearity offers a novel approach for rapid and sensitive pharmaceutical characterization.

Purpose of the Study:

• To report improvements to an optical nonlinearity-based method for pharmaceutical analysis.
• To characterize drug polymorphism and concentration in powdered and tablet forms.
• To assess the potential of this technique for pharmaceutical manufacturing process monitoring.

Main Methods:

• Utilized an apparatus measuring nonlinear optical response via second harmonic generation (SHG).
• Applied the SHG technique to enalapril maleate-polyvinylpyrrolidone (PVP) tablets for concentration determination.
• Characterized ranitidine hydrochloride (RN) polymorph forms I and II using SHG.
• Investigated particle size and angular dependence of SHG response in crystalline lactose.

Main Results:

• The SHG method successfully determined drug concentration in tablets with a limit of detection around 1%-2%.
• Pure and mixed (50:50) ranitidine hydrochloride polymorphs (I and II) were clearly distinguished.
• SHG response showed a monotonic decrease with increasing particle size for crystalline lactose.
• Angular dependence of scattered SHG light was investigated for crystalline lactose.

Conclusions:

• The improved optical nonlinearity method, particularly SHG, is effective for pharmaceutical polymorphism and concentration characterization.
• The technique demonstrates rapid and clear distinction between different drug forms and concentrations.
• This method shows significant promise for real-time monitoring in pharmaceutical manufacturing.