Abstract
Crystalline salbutamol sulphate (SS) is a common β2-agonist used in dry powder inhalers for the treatment of asthma. The solid-state characteristics of SS are import since they govern the stability, and thus efficacy of the drug when incorporated in inhalation medicine. Previous studies have investigated the thermal properties of SS and the complex array of thermal events have been attributed a mixture of melting and/or degradation mechanisms. In order to ascertain the exact thermal transformation processes that SS undergoes, and we utilised a combination of differential scanning calorimetry coupled with quadrupole mass spectrometry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy over the temperature range 25–500 °C. Based on the coupled thermal analysis data, we proposed that SS undergoes a multi-step degradation mechanism in which the molecule dehydrates loosing water initially, followed by the break up of the secondary amine group and lastly formation of sulphur dioxide. When used in conjunction, the analytical techniques offered significant advantages over the use of thermal analysis alone, offering a better understanding of the transformations occurring to SS following heating.
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References
Op’t Holt TB. Inhaled beta agonists. Respir Care. 2007;52(7):820–32.
Anderson PJ. History of aerosol therapy: liquid nebulization to MDIs to DPIs. Respir Care. 2005;50(9):1139–50.
Crompton G. A brief history of inhaled asthma therapy over the last 50 years. Prim Care Respir J. 2006;15(6):326–31.
Giron D. Characterisation of salts of drug substances. J Therm Anal Calorim. 2003;73(2):441–57.
Caira MR, Bourne SA, Oliver CL. Thermal and structural characterization of two polymorphs of the bronchodilator tolbuterol. J Therm Anal Clarorim. 2004;77(2):597–605.
Silva ACM, Galico DA, Guerra RB, Legendre AO, Rinaldo D, Galhiane MS, Bannach G. Study of some volatile compounds evolved from the thermal decomposition of atenolol. J Therm Anal Calorim. 2014;115(3):2517–20.
Brodka-Pfeiffer K, Langguth P, Grass P, Häusler H. Influence of mechanical activation on the physical stability of salbutamol sulphate. Eur J Pharm Biopharm. 2003;56(3):393–400.
Raula J, Thielmann F, Kansikas J, Hietala S, Annala M, Seppälä J, et al. Investigations on the humidity-induced transformations of salbutamol sulphate particles coated with l-leucine. Pharm Res. 2008;25(10):2250–61.
Jetmalani K, Young PM, Smith T, Stewart P, Traini D. Micronized drug powders in binary mixtures and the effect of physical properties on aerosolization from combination drug dry powder inhalers. Drug Dev Ind Pharm. 2012;38(12):1504–11.
Igo DH, Bis JA, Carino SAR, Chen P, Katrincic LA, Kinder DS, et al. Albuterol sulfate: discovery and attributes of new crystalline forms. In: Dalby RBR, Byron PR, Peart J, Suman J, Farr SJ, Young P, editors. Proceedings of Respiratory Drug Delivery; 2012. pp. 437–40.
Ward GH, Schultz RK. Process-induced crystallinity changes in albuterol sulfate and its effect on powder physical stability. Pharm Res. 1995;12(5):773–9.
Curtin V, Amharar Y, Gallagher KH, Corcoran S, Tajber L, Corrigan OI, et al. Reducing mechanical activation-induced amorphisation of salbutamol sulphate by co-processing with selected carboxylic acids. Int J Pharm. 2013;456(2):508–16.
Larhrib H, Martin GP, Marriott C, Prime D. The influence of carrier and drug morphology on drug delivery from dry powder formulations. Int J Pharm. 2003;257(1–2):283–96.
Felix FS, Cides da Silva LC, Angnes L, Matos JR. Thermal behavior study and decomposition kinetics of salbutamol under isothermal and non-isothermal conditions. J Threm Anal Calorim. 2009;95(3):877–80.
NIST Mass Spec Data Center, Stein SE, director. Infrared spectra. In: NIST Chemistry WebBook, NIST Standard Reference Database Number 69. National Institute of Standards and Technology. 2013. http://webbook.nist.gov/chemistry. Accessed 21 Aug 2013.
Corrigan D. Predicting the physical state of spray dried composites: salbutamol sulphate/lactose and salbutamol sulphate/polyethylene glycol co-spray dried systems. Int J Pharm. 2004;273(1–2):171–82.
Coates J. Interpretation of infrared spectra, a practical approach. In: Meyers RA, editor. Encyclopedia of analytical chemistry. Chichester: Wiley; 2000. p. 10815–37.
Mälkki L, Tammilehto S. Decomposition of salbutamol in aqueous solutions. I. The effect of pH, temperature and drug concentration. Int J Pharm. 1990;63(1):17–22.
Mälkki-Laine L, Bruins AP. Structural characterization of the decomposition products of salbutamol by liquid chromatography—ionspray mass spectrometry. J Pharm Biomed Anal. 1994;12(4):543–50.
Mälkki-Laine L, Purra K, Kähkönen K, Tammilehto S. Decomposition of salbutamol in aqueous solutions. II. The effect of buffer species, pH, buffer concentration and antioxidants. Int J Pharm. 1995;117(2):189–95.
Cope M, Bautista-Parra F. The degradation of salbutamol in ethanolic solutions. J Pharm Biomed Anal. 2010;52(2):210–5.
Acknowledgements
A/Professor Young is the recipient of an Australian Research Council Future Fellowship (project number FT110100996). A/Professor Traini is the recipient of an Australian Research Council Future Fellowship (project number FT12010063). The authors would like to thank Jean-Pierre Guerbois of UTS Science for the invaluable help on the use of DSC/MS.
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Sonvico, F., Coleman, V., Traini, D. et al. Evolved gas analysis during thermal degradation of salbutamol sulphate. J Therm Anal Calorim 120, 789–794 (2015). https://doi.org/10.1007/s10973-014-3935-8
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DOI: https://doi.org/10.1007/s10973-014-3935-8