Enantioselective resolution of Rac‐terbutaline and evaluation of optically pure R‐terbutaline hydrochloride as an efficient anti‐asthmatic drug

Abstract

Terbutaline is a β -adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R-isomer was found to be the potent enantiomer in generating therapeutic effect, while S-isomer has been reported to show side effects. In this study, R-terbutaline hydrochloride (R-TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac-TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R-TBH 6 nebulized solution was prepared in half dosage of Bricanyl®, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti-asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R-TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti-asthmatic effect with Bricanyl®.

Clinical value of N-acetylcysteine combined with terbutaline sulfate in elderly patients with chronic obstructive pulmonary disease and its effect on apoptosis/anti-apoptosis mechanism

“…Terbutaline sulfate is an important therapeutic drug for COPD, which can act on the respiratory tract at a higher concentration after compressed nebulization and inhalation, activating adenosine cyclase and increasing the content of cyclic adenosine and ribonucleic acid in cells. As a kind of short-acting β2 receptor agonist, terbutaline sulfate can also excite β2 receptors to relax the smooth muscle of the respiratory tract, inhibit the production of inflammatory mediators, expand airways, enhance cilia movement, promote sputum discharge, and finally improve the ventilation function of the lung (9). Concurrently, terbutaline sulfate can stimulate alveolar type II cells to synthesize and secrete pulmonary surfactant, which can reduce the viscosity of mucopolysaccharides, and promote sputum secretion (10).…”

Chiral separation of terbutaline by supercritical fluid chromatography with peak purity determination by UPLC–MS and modeling for chiral recognition mechanism

“…Terbutaline is the most effective drug to treat this disease. [1][2][3] Terbutaline is a selective ⊎ 2 -adrenoceptor agonist. Terbutaline sulfate, chemically ⊎-[(tert-butylamino) methyl]-3,5-dihydroxy-benzyl alcohol (C 12 H 19 NO 3 ), is a synthetic ⊎ 2 -adrenoceptor (⊎ 2 AR) agonist and generally used as a bronchodilator (Fig.…”

“…Nowadays, asthma is the most common chronic disease found in all age groups and about 300 million people are suffering from this disease globally. Terbutaline is the most effective drug to treat this disease 1‐3 . Terbutaline is a selective β 2 ‐adrenoceptor agonist.…”

Quality-by-Design Is a Tool for Quality Assurance in the Assessment of Enantioseparation of a Model Active Pharmaceutical Ingredient

“…Terbutaline (TER) (Figure 1) is a selective β2-agonist, therapeutically used as a fast-acting bronchodilator and tocolytic agent. It is marketed by many pharmaceutical companies as a racemic mixture (racTER) i.e., an equal ratio of the (R) eutomer and (S) distomer [28,29]. In 1992, the FDA highlighted that the determination of the different enantiomers is necessary and cannot be ignored since the enantiomers of a biologically active chiral compound often behave differently in pharmacokinetic and pharmacological activity.…”