Salbutamol formulations

Nogami-Itoh, M., I.Yakuo, D.M.Hammerbeck, R.I.Miller, and K.Takeyama. 1997. The equivalent bronchodilator effects of salbutamol formulated in chlorofluorocarbon and hydrofluoroalkane-134a metered dose inhalers on the histamine-induced pulmonary response in dogs. Pharmaceut. Res. 14 208-212. 

An asthmatic patient whose salbutamol formulation was replaced by another containing benzalkonium chloride as an excipient developed bronchospasm as a result (3). 

Wu T, Pao W, Chen J, Shang R. Formulation optimization technique based on artificial neural network in salbutamol sulfate osmotic pump tablets. Drug Dev Ind Pharm 2000 26 211-15. 

Data have been obtained with this set-up for several different types of MR products and the ability to predict food effects, at least on a qualitative basis, appears to be very promising. An example of a known food effect which can be simulated in vitro is that of a salbutamol MR formulation. The in vitro results are shown in Figure 12. 

The transformation of a drug into a medicinal product is a complex process that is controlled by a range of competing factors. The formulator must amalgamate the preformulation information and the clinical indication, which may suggest a particular route of administration (e.g. inhalation of salbutamol. Table 2.2), with toxicology and biopharmaceutical data determining... 

CEC-based metered-dose therapeutic aerosols are in the process of being reformulated with HEA-134a. HEA-formulations of salbutamol (= albuterol) and fluticasone propionate have been shown to be as effective and well tolerated as CEC products at equivalent doses. 

Salbutamol may be administered parenterally as an intravenous infusion at 3-20 pg min-1 with the dose being titrated to therapeutic effect. Side effects notably tachycardia are more common with parenteral or nebulised formulations. The drug may also be administered by the subcutaneous or intramuscular routes. Salbutamol is conjugated in the liver and excreted both in the urine as unchanged drug and metabolites, and also in the faeces. 

Taha El, Zaghloul A A, Kassem AA, Khan MA. Salbutamol sulfate suppositories influence of formulation on physical parameters and stability. Pharm Dev Technol 2003 8(1) 21 30. 

Cheng YS, Fu CS, Yazzie D, Zhou Y. Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulations in a human airway replica. J Aerosol Med 2001 14(2)255-266. 

Zeng XM, Martin GP, Tee SK, Ghoush AA, Marriott C. Effects of particle size and adding sequence of fine lactose on the deposition of salbutamol sulphate from a dry powder formulation. Int J Pharma 1999 182 133-144. 

What formulations of salbutamol and inhaled corticosteroids are available and what are the advantages and disadvantages ... 

Salbutamol is available as tablets, inhalers, nebuliser solution and intravenous injection. In the management of asthma at step 1 and 2 the inhaled formulation is the best option since it targets the drug and minimises side-effects. Oral tablets of salbutamol are rarely used and there is limited evidence of their effectiveness. 

Argekar, A.P. Powar, S.G. Simultaneous determination of salbutamol sulfate and bromhexine hydrochloride in formulations by quantitative thin layer chromatography. J. Planar Chromatogr.-Mod TLC 1998,11, 254-257. 

M.C.R. Production of spraydried salbutamol sylphate for use in dry powder aerosol formulation. Int. J. Pharm. 

More patients using the hydrofluoroalkane (18%) withdrew from the study than patients using the chlorofluorocarbon (4.8%). Most of the withdrawals in both groups were unrelated to safety (9 and 3.2% respectively). The reasons for withdrawal included intercurrent illness, loss to followup, and inadvertent prescription errors. More patients using the hydrofluoroalkane withdrew because of an adverse event or because of the taste of the inhaler, 3.8 versus 0.9% and 3.1 versus 0.2% respectively. The authors concluded that the data supported the evidence already obtained in clinical trials that reformulation of salbutamol in a hydrofluoroalkane propellant does not result in changes in safety compared with a chlorofluorocarbon formulation. 

The issue of enantioselective efficacy and safety of salbutamol has been reviewed (1). Interest in chiral switch, that is the replacement of the racemic formulation by the pharmacologically active (i )-enantiomer levosalbutamol, may be hampered by enantiomeric interconversion in vivo and marked interindividual variation in salbutamol pharmacokinetics and pharmacodynamics, owing to complex interactions between genetic and environmental effects. The authors concluded that the advantage of levosalbutamol over the racemic formulation appears to be small with respect to efficacy and controversial with respect to safety. Two large crossover studies with multiple inhaled doses of (5 )-salbutamol in asthmatic patients showed no evidence of adverse effects on FEVi (2,3). 

Salbutamol (albuterol) is a beta2-adrenoceptor agonist used to treat asthma. It is available in various formulations ... 

A modified-release formulation of salbutamol (ProventU Repitabs) 12 mg bd was well tolerated in children. There were no serious adverse events and no changes in vital signs or the electrocardiogram (SEDA-21,182). 

Inhalation of the intravenous formulation of tobramycin can cause bronchoconstriction, as has been confirmed in 26 children with mild to moderate cystic fibrosis (11). Nevertheless, while bronchoconstriction did occur, many patients did not have bronchoconstriction in response to the standard intravenous formulation. The risk of bronchoconstriction may further be reduced by pretreatment with salbutamol. 

For certain substances it is generally accepted that in conventional orcil pharmaceutical formulations they do not cause bioequivalence problems. That is why the MEB does not consider it necessary to perform and submit bioequivalence research for the following 19 substances amoxicilline, dextromethorfan, diazepam, doxycycline, potassiumfenoxymethylpenicillin, flunarizine, indometacine, isosorbide-5-mononitrate, lorazepam, lormetazepam, metoprolol, naproxen, nitrazepam, oxprenolol, paracetamol, pindolol, piroxicam, salbutamol, temazepam. According to the MEB there is enough evidence present in literature to prove that there is no problem with the bioequivalence. 

Aboul-Enein, H. Y. and Abu-Zaid, S. Two-dimensional TLC method for identification and quantitative analysis of salbutamol and related impurities in pharmaceutical tablet formulation. Anal. Lett. 34 2099-2110, 2001. 

Combinations of medications has been common practice for the treatment of COPD. There is evidence of increased efficacy of combinations of the (3-adrenoceptors agonists and cholinergic receptor antagonists. Such combined therapy has recently been introduced, e.g., Combivent , which is an aerosol formulation of the (3-adrenoceptor agonist, salbutamol, and ipratropium [86]. 

H. Leon-Molina, F. Flores-Murrieta, and R. Chapela, Assessment of comparative bioequivalence of two metered-dose inhaler formulations of salbutamol— measuring bron-chodilatory effect in patients with asthma. Clin Drug Invest 22(7) 435-441 (2002). 

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