Spectrophotometric Determination of Bromhexine HCl in Pure and Pharmaceutical Forms

Five spectrophotometric methods for determination of bromhexine HCl have been developed, validated, and applied for the assay of the drug in pharmaceuticals. Methods A, B, and C are based on ion-pair complexation of drug, in acidic buffers, with triphenylmethane dyes, namely, bromothymol blue (BTB), bromophenol blue (BPB), and bromocresol green (BCG). The complexes are extracted into chloroform, and absorbance is measured at around 415？nm as function of concentration of the drug. The stoichiometry of the complex is found to be 1？:？1 in each case. Method D depends upon charge-transfer complexation of neutralized drug with iodine which produces iodide ion whose absorbance at 366？nm is measured as function of concentration of the drug. This complex too has 1？:？1 composition as determined by Job’s method. Method E is developed on the basis of oxidation of the drug with alkaline KMnO4 which generates green-colored manganate ion with 610？nm. As the intensity of green color increased with increasing time kinetics of the reaction is followed, and calibration curves are constructed by using initial rate and fixed time methods. Excellent recovery studies with high accuracy and precision indicate that the methods can be successfully used in industries for the assay of drug in pure form and pharmaceuticals. 1. Introduction Bromhexine HCl (BRH), chemically named 2-amino-3,5-dibromo-N-cyclohexyl-N-methyl benzenemethanamine hydrochloride, is a mucolytic agent used in the treatment of respiratory disorders associated with viscid or excessive mucus [1, 2]. The drug is official in IP [3] and BP [4]. Because of its physiological importance, the drug has been quantified by exploiting its chemical [5, 6] and physical properties [7–25]. The different analytical methods used to quantify the drug as a single active pharmaceutical ingredient include flow injection analysis with ion-selective electrodes [7], inductively coupled plasma mass spectrometry [8], electrokinetic chromatography [9], electrochemical oxidation at the glassy carbon electrode [10], liquid chromatography [11], liquid gas chromatography [12], GC with mass detection [13], and voltammetry [14]. The drug has also been quantified in its combined formulations using HPLC [15–18], direct and derivative UV spectrophotometry [19–23]. These methods involve scarcely available costly equipment and tedious experimentation. Simple, accurate, and precise methods using spectrophotometry have also been developed based on the production of chromophore by the interaction of the drug with an analytical reagent, as chromogen