Development, validation and comparison of near infrared and Raman spectroscopic methods for fast characterization of tablets with amlodipine and valsartan.

The objective of this study was to develop, validate and compare NIR and Raman spectroscopic methods for fast characterization in terms of API content and tensile strength of fixed-dose combination tablets containing amlodipine and valsartan. For the APIs assay NIR-transmittance and Raman-reflectance methods were considered, whereas for the tensile strength assay Raman spectra were recorded in reflectance configuration and NIR spectra were recorded in both reflectance and transmittance. Multivariate calibration models (PLS) were built by applying different pre-processing methods (SNV, MSC, SD+SNV) on certain spectral regions. Correlating pre-processed spectral data with tablet properties resulted in highly predictive models except in the case of NIR-transmittance spectra for tensile strength estimation. The best models selected by cross-validation were further validated on independent samples in terms of linearity, trueness, accuracy and precision. Using Bland and Altman analysis the analytical performance of the NIR and Raman methods were compared, demonstrating their similarity considering the investigated applications. The two spectroscopic methods can be used in association to confirm each others results for at-line characterization of the pharmaceutical product.

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system.

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained.