Physicochemical Properties and Solubility of Hydrochloride Mucolytic Agents

Abstract

Two widely used active pharmaceutical ingredients (API), ambroxol hydrochloride (AMB·HCl) and bromhexine hydrochloride (BMH·HCl), belong to the expectorant and mucokinetic group of drugs. Their applications are found in the treatment of the upper respiratory tract and bronchopulmonary diseases. The compounds have similar chemical structures, but are different enough to distinguish their physicochemical properties. To understand better the bioavailability of the drugs a series of experiments was performed to establish significant parameters. With differential scanning calorimetry (DSC) the temperature and the enthalpy of fusion were determined with no observed polymorphic transformations. The phase diagrams for binary systems {active agent (1) + solvent (2)} were determined with three solvents: 1-octanol, water and ethanol, to describe phase equilibria by correlation with the local composition models: Wilson, UNIQUAC and NRTL. Finally, the Bates–Schwarzenbach method was used to establish the ionization constants of AMB·HCl and BMH·HCl at two temperatures: room temperature 298.2 K and human body temperature 310.2 K. Our study can give an insight into further drug delivery system design and help to create more effective drug application forms.

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

“…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 stability of the drug [27,44]. Koivisto et al [45] reported that Mg stearate (excipient as well) properties strongly depend on the moisture content and its hydration state [21]. Literature data confirm that magnesium stearate might absorb moisture during storage under relative humidity greater than approximately 85% [46].…”

“…stability of the drug [27,44]. Koivisto et al [45] reported that Mg stearate (excipient as well) properties strongly depend on the moisture content and its hydration state [21]. Literature data confirm that magnesium stearate might absorb moisture during storage under relative humidity greater than approximately 85% [46].…”

“…Most excipients used for Flavamed ® formulation are stable up to 300 • C. The last stage (IV stage-318-800 • C) is attributed to the excipients decomposition reactions, including the primary and secondary released products and the carbonization processes. Excipients such as corn starch [40], PVP [3], croscarmellose sodium excipient [58], magnesium stearate and powdered cellulose [21,59], are disintegrated here.…”

“…There is no detailed and comprehensive research on ambroxol hydrochloride thermal decomposition and its stability in the current literature. Podbukowska et al reported on some physicochemical properties of AMB: solubility, acidity constant determination, and thermophysical data [21]. Caira et al investigated the thermal and structural properties of ambroxol polymorphs [22].…”

Study of the flow mechanism and influencing factors of sputum excretion from the distal lung

“…In addition to relying on the swing of cilia on the bronchial wall to push sputum out (Paplińska-Goryca et al , 2020), most of the other sputum expulsion methods involve different fluid dynamic mechanisms. Drugs are generally used to accelerate the secretion of body fluid to reduce the dynamic viscosity of sputum and promote sputum excretion (Pobudkowska et al , 2021). When people can breathe autonomously, they can instantaneously produce large air velocity through severe coughs (Bourouiba et al , 2014; Wei and Li, 2017) and push the sputum upward with the help of inertia.…”