Thermo-Analytical and Compatibility Study with Mechanistic Explanation of Degradation Kinetics of Ambroxol Hydrochloride Tablets under Non-Isothermal Conditions

Ambroxol hydrochloride (AMB), used as a broncho secretolytic and an expectorant drug, is a semi-synthetic derivative of vasicine obtained from the Indian shrub Adhatoda vasica. It is a metabolic product of bromhexine. The paper provides comprehensive and detailed research on ambroxol hydrochloride, gives information on thermal stability, the mechanism of AMB degradation, and data of practical interest for optimization of formulation that contains AMB as an active compound. Investigation on pure AMB and in commercial formulation Flavamed® tablet (FT), which contains AMB as an active compound, was performed systematically using thermal and spectroscopic methods, along with a sophisticated and practical statistical approach. AMB proved to be a heat-stable and humidity-sensitive drug. For its successful formulation, special attention should be addressed to excipients since it was found that polyvinyl pyrrolidone and Mg stearate affect the thermal stability of AMB. At the same time, lactose monohydrate contributes to faster degradation of AMB and change in decomposition mechanism. It was found that the n-th order kinetic model mechanistically best describes the decomposition process of pure AMB and in Flavamed® tablets.

UV-spectrophotometry-assisted chemometric methods for simultaneous determination of ambroxol hydrochloride and doxofylline in pharmaceutical formulation

Two methods, ratio spectra derivative method and partial least squares regression (PLS) were developed for the simultaneous estimation of ambroxol hydrochloride and doxofylline in combined dosage form. In the first method, ratio spectra derivative method, analytical signals were measured at the wavelengths corresponding to either maximums or minimums for both drugs in the first derivative spectra of the ratio spectra obtained by dividing the standard spectrum of one of two drugs in water. Partial least squares regression (PLS) was used for data analysis of and the parameters of the chemometry procedures were optimized. In this study, the simultaneous determination of ambroxol hydrochloride and doxofylline in pharmaceuticals by chemometric approaches using UV spectrophotometry has been reported. Spectra of ABH and DOX were recorded at several concentrations within their linear ranges between 2-12 μg/mL and 15-40 μg/mL respectively and applied to pharmaceutical formulation, tablet, with no interference with excipients as indicated by the results of the recovery study. The proposed methods are simple, rapid and can be easily used in the quality control of drugs as alternative analytical tools.