Stress Degradation Studies and Development of Stability Indicating Assay Method for Simultaneous Estimation of Ambroxol Hydrochloride and Salbutamol Sulphate in Bulk and Its Formulation

Abstract

Simple, rapid, precise, and accurate, reversed phase high performance liquid chromatographic method was developed and validated for simultaneous determination of Salbutamol Sulphate (SALB) and Ambroxol Hydrochloride (AMBR). The chromatographic separation was achieved on Grace 4.6 (id) x 250 mm column at detector wavelength of 224 nm, using an mobile phase consisting of phosphate buffer and acetonitrile in a ratio of 50:50 at pH 3.0 with a flow rate 1 ml/min. The retention time for Salbutamol Sulphate (SALB) and Ambroxol Hydrochloride (AMBR) were found to be 3.8 and 6.2 respectively. The method showed adequate precision with a relative standard deviation (RSD) smaller than 3%. The accuracy was analyzed by adding a standard drug and good recovery values were obtained for all drug concentration used. The HPLC method developed in this study showed specificity and selectivity with linearity in the working range and good precision and accuracy, making it very suitable for quantification of Salbutamol Sulphate and Ambroxol Hydrochloride in tablet dosage form. Degradation studies were carried out under conditions of Alkali Degradation, Acid Degradation, dry heat Degradation, Peroxide Degradation, and UV light and the drug substances were degraded in all conditions. Force degradation studies shows all the degradant peak obtained during degradation were well resolved from main peak of the drugs. The analytical procedure is reliable and offers not only advantages in terms of speed but also met the regulatory requirements for specificity, Linearity, LOD, LOQ, Precision, accuracy.

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

“…Such findings could be potentially attributed to the previous moisture effect. In addition, it should be noted that lactose monohydrate, one of the excipients in FT formulation, also interacts with moisture-sensitive drugs and affect the Pharmaceutics 2021, 13, x FOR PEER REVIEW 11 of 30 [41][42][43], or thermal stability via drug-drug interactions [25]. It was noted that ambroxol hydrochloride degrades extensively under acid, alkali, and oxidative conditions, considered during storage time [41].…”

“…Ac cording to the literature data, the stability of ambroxol hydrochloride was mainly studied through the stress degradation approach according to ICH (International Council for Har monisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines For the evaluation of AMB thermal stability from the kinetic point of view, thermal decomposition of ambroxol hydrochloride and Flavamed ® tablet was recorded using multiple heating rates, i.e., non-isothermal conditions as follows: AMB (β = 5, 10, and 20 • C/min) (Figure 5) and FT (β = 5, 10, and 30 • C/min) (Figure 6) in an N 2 atmosphere. According to the literature data, the stability of ambroxol hydrochloride was mainly studied through the stress degradation approach according to ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines [41][42][43], or thermal stability via drug-drug interactions [25]. It was noted that ambroxol hydrochlo-ride degrades extensively under acid, alkali, and oxidative conditions, considered during storage time [41].…”

“…According to the literature data, the stability of ambroxol hydrochloride was mainly studied through the stress degradation approach according to ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines [41][42][43], or thermal stability via drug-drug interactions [25]. It was noted that ambroxol hydrochlo-ride degrades extensively under acid, alkali, and oxidative conditions, considered during storage time [41].…”

“…Pharmaceutics 2021, 13, x FOR PEER REVIEW 11 of 30 [41][42][43], or thermal stability via drug-drug interactions [25]. It was noted that ambroxol hydrochloride degrades extensively under acid, alkali, and oxidative conditions, considered during storage time [41].…”