Desarrollo galénico de una cápsula que contiene minicomprimidos de Rosuvastatina, Repaglinida y Olmesartan para el tratamiento del Síndrome Metabólico

Resum

This research project studies the possibility of improving adherence to treatment in patients with metabolic syndrome. To this end, a capsule containing mini tablets of rosuvastatin, repaglinide and olmesartan, used in the treatment of this pathology, was developed to reduce the number of tablets that the patient has to administer and the number of administrations. Accordingly, a methodology was proposed for the design, development and characterization of tablets prepared by direct compression for each of the active ingredients. The design was based on a careful selection of excipients that, due to their characteristics and proportions within each formulation, allowed to take advantage of their properties such as fluidity or granulometric distribution. The formulations were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD) methods. In addition, the SeDeM galenic methodology was used to establish the profile of the selected active ingredient-excipient mixture and ensure its suitability to produce tablets by the direct compression method. At the same time, a simple, rapid, and highly sensitive analytical method for the detection, separation, and quantification of N-nitrosodimethylamine in the active substance olmesartan medoxomil, as well as in the manufactured and marketed tablets, was developed and validated using high-performance liquid chromatography-mass spectrometry. The validated method can be used routinely for the determination and quantification of N-nitrosodimethylamine in olmesartan. Finally, the pharmaceutical technological characteristics of the manufactured tablets were determined. The formulation of the three tablets complied with pharmacopoeia guidelines in terms of content uniformity, tablet hardness, thickness, friability, in vitro disintegration time and dissolution profile.