Preparation And Evaluation Of A Novel R-terbutaline Nebulizer For Treatment Of Asthma

Terbutaline,a rapid-acting ?2-adrenergic receptor agonist,is used as a bronchodilator for the treatment of asthma and chronic obstructive pulmonary diseases in the clinic.Terbutaline is a chiral durg,and only the racemate has been approved worldwide.Studies have showned that R-enantiomer of terbutaline generates the therapeutic effect,while its S-enantiomer is therapeutically ineffective and possesses certain toxicities and side effects such as increasing airway hyperresponisiveness and cardiac adverse events.So far,no researches about formulation of R-terbutaline hydrochloride had been reperoted.Therefore,the aim of this study was to develop the formulation for inhalation of the optically pure R-enantiomer of terbutaline hydrochloride.The details were as follows,(1)The optically pure R-terbutaline hydrochloride was kindly obtained from Dongguan Key-Pharma Biomedical Co.,Ltd.Then the quality research was conducted according to the requirments of Chinese Pharmacopoeia(2015),including characters,identification,optical rotation,loss on drying,assay,related substances,S-enantiomer;Then the stability of R-terbutaline hydrochloride under heat,humidity and light was carried out.The stability data showed that R-terbutaline hydrochloride was stable varies with time,but greatly influenced by light and heat.So this would be considered in formulation part.(2)Then R-terbutaline hydrochloride solution for nebulization was prepared;Its quality research was conducted according to ChP(2015);Then three batches of its solution for nebulization were prepared.Then their stress testing and stability under accelerated condition and long-term condition were carried out.So far,the result of stability studies showed this two formulations were all stable.(3)The aerodynamic size distribution of this two formulation and Bricanyl was tested by using the new generation pharmaceutical impactor(NGI)according to ChP(2015).And the result of in-vitro particle size distribution of this two formulation showed no significant difference when compared with Bricanyl.(4)We constructed acute asthma model of guinea pig by using histamine as a stimulant.The pharmacodynamics of R-terbutaline and double-dosage of racemic terbutaline was observed to relieve the airway hyperreponsiveness of guinea pig after aerosolizing the low,medium and high doses of drugs.It showed there has greatly significant difference when compared with the blank stimulus.While there is no significant difference between R-terbutaline group and double-dosage racemic terbutaline group,which means that the S-enantiomer of terbutaline have no efficacy and support the importance for the development of R-terbutaline.