Decomposition of salbutamol in aqueous solutions. II. The effect of buffer species, pH, buffer concentration and antioxidants

Mälkki-Laine, Liisa; Purra, Kirsi; Kähkönen, Kaarina; Tammilehto, Seija

doi:10.1016/0378-5173(94)00329-4

Cited by 14 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 Although chemical degradation of albuterol sulfate in aqueous solutions has been studied, 9 it is uncertain whether the chemistry in aqueous solutions is related to that in propellant formulations.…”

Section: Introductionmentioning

confidence: 99%

Drug Form Selection in Albuterol-Containing Metered-Dose Inhaler Formulations and Its Impact on Chemical and Physical Stability

Tzou¹,

Pachuta²,

Coy³

et al. 1997

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

New albuterol-containing metered-dose inhaler (MDI) formulations were under development to replace chlorofluorocarbon (CFC) propellants with more environmentally friendly hydrofluoroalkane (HFA) propellants. To achieve good chemical and physical stability of MDI formulations with HFA propellants, different drug forms were evaluated in model formulations (drug, oleic acid, and one of the following: P12/P11, P12/ethanol, P12, P134a/ethanol, P134a). The effects of drug form (base versus sulfate), propellant type (P12 versus P134a), and cosolvent type (P11 or ethanol versus none) on the chemical and physical stability were examined. The chemical stability of the formulations was determined by monitoring the percent drug remaining in the formulations using HPLC. The physical stability of the formulations was followed by visually assessing the suspension appearance, and by determining the mass median diameter (MMD) of the suspended particles using laser diffraction analysis. The drug form has a great impact on the chemical and physical stability of the formulations. The sulfate formulations were chemically stable up to 12 months when stored at 30 degrees C and 40 degrees C/85% relative humidity (RH). Poor chemical stability was observed for the base formulations, except for ethanol-free formulations (P12/P11, P12, and P134a) at 30 degrees C and a P134a formulation at 40 degrees C/85% RH. The chemical instability of albuterol base formulations at 30 degrees C correlates with its solubility. The presence of a cosolvent greatly improved the dispersion characteristics of both sulfate and base formulations. The sulfate formulations in the presence of a cosolvent (P12/P11, P12/ethanol, and P134a/ethanol) showed good physical stability when stored for up to 12 months at 30 degrees C and 40 degrees C/85% RH. The physical stability of the base formulations was not acceptable due to crystal growth/agglomeration in all formulations, except for the P12/P11 formulation. The physical instability of both sulfate and base formulations not only correlates with the drug solubility, but also with particle agglomeration. In conclusion, good chemical and physical stability of albuterol-containing suspension formulations can be achieved with the appropriate choice of drug form and formulation constituents.

show abstract

Section: Introductionmentioning

confidence: 99%

Drug Form Selection in Albuterol-Containing Metered-Dose Inhaler Formulations and Its Impact on Chemical and Physical Stability

Tzou¹,

Pachuta²,

Coy³

et al. 1997

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Even if not evaluated through the DoEs, this could be ascribed to an interaction between these variables. Moreover, it has been previously demonstrated that autoclaving SLBT in acetate buffers causes its degradation [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Polar licit and illicit ingredients in dietary supplements: chemometric optimization of extraction and HILIC-MS/MS analysis

Baglietto,

Benedetti,

Di Carro

et al. 2024

Anal Bioanal Chem

View full text Add to dashboard Cite

Many dietary supplements claim the ability to enhance sports performance and to improve the fitness of the consumers. Occasionally, along with legal ingredients, illicit compounds may be added without being labelled, leading to unintended doping. Hence, the aim of this study was to develop an analytical method to determine a set of 12 polar (logDpH=7 from −2.0 to +0.3) compounds including diuretics, stimulants, β2-agonists, methylxanthines, and sweeteners. Hydrophilic interaction liquid chromatography was chosen as separation strategy, coupled with tandem mass spectrometry. The instrumental method was optimized using a two-step design of experiments (DoE). Firstly, a Plackett–Burman (PB) DoE was performed to identify the more influencing variables affecting peak areas and chromatographic resolution among temperature, water percentage in the mobile phase, and flow rate, as well as type and concentration of buffers. Secondly, a D-optimal DoE was set, considering only the most significant variables from the PB-DoE results, achieving a deeper understanding of the retention mechanism. Sample processing by salt-assisted liquid–liquid extraction was studied through DoE as well, and the whole method showed recoveries in the range 40–107% and procedural precision ≤11% for all analytes. Finally, it was applied to real samples, in which the four methylxanthines and two artificial sweeteners were detected and quantified in the range of 0.02–192 mg g−1. These values were compared to the quantities declared on the DS labels, when possible. Furthermore, a sequence of MS/MS scans allowed detection of a signal in one of the samples, structurally similar to the β2-agonist clenbuterol. Graphical Abstract

show abstract

“…Salbutamol sulfate has proved to have better chemical and physical stability than salbutamol while in racemic form 28 . Research on the decomposition of salbutamol sulfate in aqueous solution indicates that the maximum stability of salbutamol in aqueous solution occurred at an acidic pH 29,30 . Pharmaceutical requirements for an inhalation solution need to be considered carefully.…”

Section: Resultsmentioning

confidence: 99%

An aerosol formulation of R-salbutamol sulfate for pulmonary inhalation

Zhang

Liu

et al. 2014

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

An aerosol formulation containing 7.5 mg of R-salbutamol sulfate was developed. The aerosol was nebulized with an air-jet nebulizer, and further assessed according to the new European Medicines Agency (EMA) guidelines. A breath simulator was used for studies of delivery rate and total amount of the active ingredient at volume of 3 mL. A next generation impactor (NGI) with a cooler was used for analysis of the particle size and in vitro lung deposition rate of the active ingredient at 5 °C. The anti-asthmatic efficacy of the aerosol formulation was assessed in guinea pigs with asthma evoked by intravenous injection of histamine compared with racemic salbutamol. Our results show that this aerosol formulation of R-salbutamol sulfate met all the requirements of the new EMA guidelines for nebulizer. The efficacy of a half-dose of R-salbutamol equaled that of a normal dose of racemic salbutamol.

show abstract

Decomposition of salbutamol in aqueous solutions. II. The effect of buffer species, pH, buffer concentration and antioxidants

Cited by 14 publications

References 7 publications

Drug Form Selection in Albuterol-Containing Metered-Dose Inhaler Formulations and Its Impact on Chemical and Physical Stability

Drug Form Selection in Albuterol-Containing Metered-Dose Inhaler Formulations and Its Impact on Chemical and Physical Stability

Polar licit and illicit ingredients in dietary supplements: chemometric optimization of extraction and HILIC-MS/MS analysis

An aerosol formulation of R-salbutamol sulfate for pulmonary inhalation

Contact Info

Product

Resources

About