Improvement Of Quality Standards Of Piroxicam And Tablets And Determination Of Crystal Form Of Piroxicam

Objective:To improve quality standards of piroxicam and piroxicam tablets by establish HPLC method for the determination of related substances of piroxicam and tablets,establish HPLC method for the determination of piroxicam tablets,establish gas chromatographic method for the determination of residual solvents.And study crystalline form of piroxicam.Methods:1.Related substances examination:using C18 col?mn(5?m,4.6×250mm),with the detection wavelength at 230nm.The mobile phase was composed of 0.05mol/L Potassium dihydrogen phosphate solution(adjusted to pH 3.0 with phosphoric acid)and acetonitrile with gradient elution,and the flow rate was 1.Oml/min.2.Determination:using C18 col?mn(5?m,4.6x250mm).The mobile phase was composed of methanol-buffer(citric acid 7.72g and sodium dihydrogen phosphate 5.35g,dissolved in water and diluted to 1000ml)(45:55),flow rate:1.0ml/min,the detection wavelength was 246nm.3.Residual solvents:The determination was performed on INNOWAX capillary column with FID detector using nitrogen as carrier gas and dimethylsulfoxide as solvent by temperature programming.The vial equilibrium temperature was 90?and equilibrium time was 30 min.4.Crystal form:use PXRD,IR,DSC,NIR,Raman spectroscopy,microscopic identification to determin the crystalline form of piroxicam.Dissolution was measured automatically using fiber intrinsic dissolution rates of different polymorphs of piroxicam tablets and raw materials.Results:1.Established the method for the determination of related substances:piroxicam had a good linearity in the range of 1.49?g/ml?29.84?g/ml(r=0.9995).the reference solution and the test solution were stable within 24 hours.The limit of detection was 0.2?g/ml.14 related substances can be detected,including 4 main impurities.Speculate structure of the main impurities by LC-MS.2.Established the method for determination:Accessories has no interference with piroxicam,piroxicam had a good linearity in the range of 24.73?g/ml?74.19?g/ml(r=1).the solution had a good stability in 24 hours,mean recoveries was 100.3%(RSD was 0.2%,n=9).3.Established the method for the determination of residual solvents:The 8 residual organic solvents were separated completely.Good linearity were obtained(r?0.9997);average recovery rates were 87.91%?101.65%,RSD 1.4%?2.0%(n=9).The detection limits were 0.05?1.54?g/ml.1.2-dichloroethane was confirmed by GC-MS.4.Crystalline form:after the determination,there are two crystal form P??P?of piroxicam and tablets by comparison with the literature,dissolution rate of different crystal materials and tablets are different;1.2-dichloroethane was detected in piroxicam drug and tablets which have the same crystal form of P?.Conclusions:Establised and verified the method for related substances examination,for determination,for residual solvents,improved quality standards of piroxicam and tablets.Polymorphs were studied to provide a theoretical basis for piroxicam further research.