Presented at PITTCON 2003, March 9-14 Orlando Florida IN-SITU MONITORING OF QUALITY OF PHARMACEUTICAL PRODUCTS USING LASER BREAKDOWN SPECTROSCOPY

Presented at PITTCON 2003, March 9-14 Orlando Florida TOTAL QUALITY CONTROL (TQC ) CONVENTIONAL QUALITY CONTROL: End Product TOTAL QUALITY CONTROL: At every stage of the process FOR OTHER INDUSTRY TQC IS A BUSINESS TOOL PHARMACEUTICAL INDUSTRY TQC IS LEGAL REQUIRMENT; USA FEDERAL FOOD, DRUG AND COSMETIC ACT

Presented at PITTCON 2003, March 9-14 Orlando Florida TECHNIQUES LISTED IN UNITED STATES PHARMACOPEIA WET CHEMSITRY IR,VIS,UV, ABSORPTION/FLUORESCENCE SPECTROMETRY LIGHT SCATTERING MASS SPECTROMETRY CHROMATOGRAPHY NMR (CW/FTR) X-RAY FLUORESCENCE/DIFFRACTION

Presented at PITTCON 2003, March 9-14 Orlando Florida WHY NEW TECHNIQUE All these techniques need sample preparation 1.Most of the operating costs and time are spent on the preparation of the sample for injection in the measurement device 2.Waste storage, segregation and disposal of chemicals/solvents We need a technique which needs no sample preparation

Presented at PITTCON 2003, March 9-14 Orlando Florida LASER INDUCED BREAKDOWN SPECTROSCOPY (LIBS) Almost no sample preparation Several elements can be monitored simultaneously Results are available almost immediately Optical fibers make it more convenient

Presented at PITTCON 2003, March 9-14 Orlando Florida PROBLEMS WITH LIBS Process involved ablation, atomization and excitation are complex and difficult to reproduce Careful optimization of experimental parameters to achieve detection limits and accuracy better /comparable with the alternate techniques

Presented at PITTCON 2003, March 9-14 Orlando Florida SAMPLES. wt% inwt% in wt% in wt% in Amount of brand Abrand B brand C brand D 99.99% CaCO3 CaNa CaCaMg Ca 10 tablets+0g tablets+1.00g tablets+2.00g tablets+3.00g tablets+4.00g tablets+5.00g

Presented at PITTCON 2003, March 9-14 Orlando Florida EXPERIMENTAL SETUP

Presented at PITTCON 2003, March 9-14 Orlando Florida OPTIMIZATION OF FOCAL SPOT

Presented at PITTCON 2003, March 9-14 Orlando Florida DELAY TIME

Presented at PITTCON 2003, March 9-14 Orlando Florida SAMPLE ROTATION

Presented at PITTCON 2003, March 9-14 Orlando Florida Absolute Intensity I ji = n X (hc/ ji ){g j /Q(T)}A ji Exp[-E j /kT] Or I ji = n X K Which is a linear relation

Presented at PITTCON 2003, March 9-14 Orlando Florida INTENSITY RATIO ( I ji ) x = n X (hc/ ji ) x [{g j /Q(T)}A ji ] x Exp[-E j /kT] x (I mn ) y =n Y (hc/ mn ) Y [{g m /Q(T)}A mn ] Y Exp[-E m /kT] Y Temperature dependence of Q is neglected T(x) =T(Y) ~T e [(I ji ) x ]/[(I mn ) y = constant[n X /n Y ]

Presented at PITTCON 2003, March 9-14 Orlando Florida LIBS SPECTRUM IN nm REGION

Presented at PITTCON 2003, March 9-14 Orlando Florida LIBS SPECTRUM IN nm REGION

Presented at PITTCON 2003, March 9-14 Orlando Florida CALIBRATION FOR ACTIVE INGREDIENT Ca

Presented at PITTCON 2003, March 9-14 Orlando Florida CALIBRATION FOR ACTIVE INGREDIENT Mg

Presented at PITTCON 2003, March 9-14 Orlando Florida CALIBRATION FOR IN-ACTIVE INGREDIENT Na

Presented at PITTCON 2003, March 9-14 Orlando Florida CALIBRATION FOR IMPURITY Al

Presented at PITTCON 2003, March 9-14 Orlando Florida CONCLUSIONS LIBS CAN BE USED IN TQC TO: SIMULTANEOUSLY MONITOR ON-LINE 1. ACTIVE INGREDIENTS 2. INACTIVE INGREDIENTS 3. IMPURITIES OF PHARMACEUTICAL PRODUCTS