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Technology (including: robots for production, Incompatibilities, drug production and analytics, CRS)
Drug stability determination by variable-parameter kinetic experiments
  1. S. Coppolino,
  2. A. Villari,
  3. I. Villari
  1. 1U.O. Farmacia, P.O. ‘Barone I. Romeo’, Patti (Messina), Italy
  2. 2Università degli Studi di Messina, Dipartimento Farmaco-Chimico, Messina, Italy

Abstract

Background The effect of environmental parameters on drugs stability is a very important piece of information in pharmaceutical field. It often requires a detailed kinetic investigation to have quantitative data on the dependence of the reaction rate constant on a physical parameter (temperature, pH, ionic strength, metal ions concentration, etc.). The common way consists in following many times the reaction, by a suitable analytical instrument for different values of a parameter and for each required parameter with a considerable expense of time and chemicals. The continuous introduction of new drugs made it necessary to develop faster analytical methods for the evaluation of their stability.

Purpose In this contribution the authors show a variable parameter method for the determination of drug stability based on a generalisation of non-isothermal analysis that takes advantage of the capabilities of modern data collecting and processing system.

Materials and methods The used method consists in carrying out kinetic experiments while varying, in a known way, the value of a physical parameter and in obtaining, trough a single experiment run, the entire dependence of the rate constants on that parameter. The experimental apparatus was made up of routine instruments and data were automatically collected and processed using commercially available software.

Results Many drugs, in solution, were analysed: acetylsalicylic acid, indomethacin, rolitetracycline, diltiazem, piroxicam and cinnoxicam following the reacting species using various analytical instruments: UV-vis spectrophotometer, fluorimeter, conductometer, polarimeter and HPLC. Validation was performed, in the same lab, by comparison to results obtained from traditional method experiments with measurements of accuracy, precision, linearity and detection limit. The results are in good agreement with those obtained using constant-parameter kinetic runs, moreover, being the results obtained in a fast way, through a simple mathematical treatment, are subjected to a minor statistical uncertainly.

Conclusions Variable parameter kinetics was an important method for the studied drugs and it can be easily used for all drugs when drug stability investigation is required.

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