Application of HPLC with optical and thermal methods in complex analysis of inter-component interactions of pharmaceutical compositions

Abstract

The variety of new drugs and the increasing requirements of the GMP (Good Manufacturing Practice for medical Products) standard applied to them require a systematic approach to the study of possible interaction of components. It is extremely important not only to ascertain the compliance of the drug with the
established requirements but also to understand the causes of undesirable deviations. Chromatographic, optical, thermal methods of analysis, provided with fairly modern and widespread equipment and mathematical apparatus, are most often used to identify inter-component interaction. The joint use of the methods allows obtaining complex and realistic information about the mixtures, to assess the state of the components during their contact, including as a result of the impact of stress conditions. Based on the results of experience with a group of multicomponent drugs analgesic, anti-inflammatory and anti-cold action formulated a unified methodological approach to the process of studying the stability of pharmaceutical substances in the composition of drug compositions. The algorithm includes the following blocks. The choice of objects (can be limited to the prescription of the drug or expanded by analogs). Detection of deviations in the IR spectra of the mixture and the sum of the spectra of individual ingredients. Evaluation of thermograms and state diagrams.
Computational and graphical analysis of the digital data Bank (allows identifying interaction products withgreater confidence in the result). HPLC (or it's variant of HPLC) analysis (to confirm the absence of significant amounts of impurities and the quantitative content of active components) at the final stage allows proving the stability of the components. The complex application of optical, chromatographic and thermoanalytical methods in combination with the influence of stress factors and (or) in the conditions of "accelerated aging" made it possible to study the processes and characterize the degradation products more effectively than each of the methods separately. The result of the research obtained data on the stability of 11 pairs of compounds:
drotaverine and magnesium, calcium stearate, drotaverine and citric acid, and the GOC drotaverine, drotaverine and croscarmellose sodium, naproxen and magnesium, calcium stearate, and the GOC naproxen, naproxen and pheniramine maleate, pheniramine maleate and the GOC, pheniramine maleate and ascorbic acid, co-grinding and heating which strengthens the processes of inter-pillar interaction.