Desenvolupament i validació d’un mètode analític amb un equip de difracció làser per a la determinació de la distribució de mida de partícula d’un API

Abstract

One of the most studied parameters in the pharmaceutical industry today is the particle size distribution of the active pharmaceutical principles (APIs). The analytical method used for this purpose is usually based on the laser diffraction technique. Some years ago, Medichem S.A. used the Malvern Mastersizer S laser diffraction instrument to carry out this type of analysis. For each of the APIs, they had a method developed and validated following quality standards that allowed them to obtain repeatability and precision of the results. At present, the company has acquired a new laser diffraction instrument, the Malvern Mastersizer 3000, which needs the development and a validation of the methods of analysis for each product. In this study we will focus specifically on the development and validation of a laser diffraction method with this new system for determining the particle size of an API that serves to treat ventricular heart arrhythmias. Due to confidentiality reasons, no further specific details of this product can be given. In order to carry out the development of the method with the new laser diffraction instrument, different parameters of the previous method and instrument are studied and, through different analysis, we will found the optimal values of the measurement with the new equipment. Specifically, we will study the type of dispersant, the sonication time, the optical properties of the material, the measurement duration, the pump and stirring rates, the stability time and the obscuration. Once the new method has been developed, it will have to be validated. The validation for this type of analytical method, according to the US Pharmacopoeia USP <1225>, requires that the precision of the measurements have to be considered. It is demonstrated that the developed and validated method allows obtaining results with adequate precision and repeatability. The obtained relative standard deviation of the results is within the required limits. Therefore, the method complies with the quality limits requested in this type of analysis and it can be used in the Quality Control laboratory