DEVELOPMENT OF HIGH-THROUGHPUT NIR-CHEMOMETRIC METHODS FOR THE CHARACTERISATION OF POWDER BLENDS FOR TABLETTING AND EXTENDED-RELEASE TABLETS WITH KETOPROFEN

This study aimed to develop and validate NIR-chemometric methods for direct quantification of ketoprofen and lactose in powder blends for tabletting, respectively, ketoprofen, lactose, and the kinetics of release from extended-release inert matrix tablets.Calibration samples were prepared using an experimental design with two variables and five levels, including 26 formulations.The in vitro release was carried out in phosphate buffer (pH = 7.4), utilising a dissolution testing device equipped with baskets at 100 rpm.The calibration algorithm for ketoprofen was obtained using as pre-treatment method FD+MSC (PLS = 7, RMSECV = 1.46) for powder blends, respectively SNV (PLS = 10, RMSECV = 3.94) for tablets in the 10000 -6098 cm -1 ; 5454 -4596 cm -1 spectral ranges.In the case of lactose, the calibration algorithm was obtained using the pre-treatment method SLS (PLS = 7, RMSECV = 1.79) for powder blends, respectively FD+SNV (PLS = 4, RMSECV = 6.45) for tablets, in the 10000 -4200 cm -1 spectral range.For kinetic release characterization, the Higuchi equation parameters were determined and correlated with the tablets' NIR spectra to develop a chemometric method to estimate the kinetic release directly.According to the experimental data, the calibration algorithms were validated with satisfactory accuracy, reproducibility and linearity. RezumatScopul acestui studiu a fost dezvoltarea i validarea metodelor NIR-chemometrice pentru cuantificarea direct a ketoprofenului i lactozei n amestecurile de pulberi pentru comprimate, respectiv ketoprofen, lactoz i cinetica eliberrii din comprimatele cu matrice inert cu eliberare prelungit.Probele de calibrare au fost pregtite conform unui design experimental cu 2 variabile i cinci niveluri, incluznd 26 de formulri.Cedarea in vitro a fost realizat n tampon fosfat (pH = 7,4), folosind un dispozitiv de testare a dizolvrii echipat cu couri, la 100 rpm.Algoritmul de calibrare pentru ketoprofen a fost obinut folosind ca metod de pretratare FD+MSC (PLS = 7, RMSECV = 1,46) pentru amestecurile de pulberi, respectiv SNV (PLS = 10, RMSECV = 3,94) pentru comprimate n intervalele spectrale 10000 -6098 cm -1 ; 5454 -4596 cm -1 .n cazul lactozei, algoritmul de calibrare a fost obinut folosind ca metod de pretratare SLS (PLS = 7, RMSECV = 1,79) pentru amestecurile de pulberi, respectiv FD+SNV (PLS = 4, RMSECV = 6,45) pentru tablete, n intervalul spectral 10000 -4200 cm -1 .Pentru caracterizarea cineticii eliberrii au fost determinai parametrii ecuaiei Higuchi i corelai cu spectrele NIR ale comprimatelor, pentru a dezvolta o metod NIR-chemometric pentru estimarea direct a cineticii eliberrii.Conform datelor experimentale obinute, algoritmii de calibrare au permis validarea metodelor cu acuratee, reproductibilitate i linearitate satisfctoare.