Characterization of Mefenamic Acid polymorphs and development of a quantitative method using NIR spectroscopy coupled to Chemometrics.

MAGGIO, RUBÉN M.; KAUFMAN, TEODORO S.; ANTONIO, MARINA

Rosario

Congreso; IV Reunión Internacional de Ciencias Farmacéuticas; 2016

Comite Organizador RICIFA-UNR-UNC

Nonsteroidal anti-inflammatory drugs are widely used for the treatment of pain and inflammation. Some NSAIDs hold polymorphism, showing variations in compaction and flow properties, stability and solubility; thus, affecting their bioavailability. Mefenamic Acid (AMF) is an NSAID that has four crystalline forms, PI and PII are the only forms that have been isolated and characterized. Both polymorphs have different solubility and stability. Thus, it is essential to have methodologies to allow rapid identification and quantification of both.The scope of this work was to develop an analytical methodology based on PLS (squares regression least partial), coupled to near infrared (NIR) data to quantify the polymorphic content of AMF in commercial tables. PI and PII were prepared and characterized following literature. Training set (N=20) was prepared containing mixtures of both polymorphs and matrix of excipients following a pre-established proportions. Samples were prepared in quadruplicate by weighing and mechanical homogenization. NIR spectra of samples were obtained by measurements in the range 400-2500 nm using a NIRS DS2500 FOSS.The data obtained were analyzed using the PLS algorithm using routines written for Matlab. Optimal calibration conditions (7 LVs, 400-2500 nm and maximum-minimum normalization) were obtained by evaluating the minimum Predicted Residual Error Sum of Squares (PRESS). The methodology was fully validated by analyzing the figures of merit during cross-validation and using an independent validation set. The optimized PLS model was successfully used to analyze the polymorphic content of commercial tablets (raw and spiked ones).In conclusion a reliable NIR-PLS to quantify polymorphs AMF was developed. Method was rapid, easy and need no sample preparation.