Preparation And Evaluation Of Amiodarone Hydrochloride Nanoemulsion

Amiodarone hydrochloride （ADHC） is one of the most common drugs used in thetreatment of arrhythmic, ventricular and supra ventricular arrhythmias. It is also used fortreating various types of organic cardiopathy, ACS（acute coronary syndrome） and so on.It is the first-line drugs for treating symptomatic atrialfibrillation and left ventriculardysfunction or chronic heart failure. However, the clinical application of ADHC islimited by its low water-solubility, low dissolubility in vitro, slow assimilation in vivoand low bioavailability. Using Nanoemulsion as a Drug carrier possess the advantage ofenhancing the water solubility of indissolvable drug, which is able to increase thesolubility of insoluble drugs. Therefore, the ADHC was prepared as nanoemulsion inorder to improve its solubility and absorption.As to our research, firstly, the basic components of the formulation weredetermined via investigating the solubility of ADHC in various vehicles. Pseudo-ternaryphase diagram we established to further screening surfactant, co-surfactants, oil phaseand Km values （the Km value is the mass ratio of surfactant and co-surfactants）. Theeffects of temperature, ion strength, pH values on the formation of nanoemulsion wereresearched also. The results showed that under the condition of Emulsifier OP^-10assurfactant, Ethyl alcohol as co-surfactant, EO as oil phase and the Km=3∶1, the bestmass ratio was obtained as Emulsifier OP^-10/absolute ethyl alcohol/EO/water=24.3∶8.1∶3.6∶64. The protocol was less surfactants using, higher loading rate andoutstanding physical stability.The ADHC nanoemulsion was prepared by using Phase inversion methodaccording to the optimized protocol, following by quality evaluation. The resultsshowed that the ADHC nanoemulsion was light, clear, transparent and good liquidityliquids. It is basic character parameters such as electric conductivity, viscosity, pH were134.8μs·cm^-1,40.27mPa·s and6.8respectively. The shape of nanoemulsion dropletswas sphere under transmission electron microscopy with an average diameter of10.06nm. The dilution stability of nanoemulsion was investigated by using1mol·L^-1HCl, pH6.8PBS and distilled water. The results showed that the bigger the dilution ratio ofdifferent media was, the smaller the particle size of nanoemulsion will be. However, theparticle size of nanoemulsion was independent of the dilution ratio after50or moredilution ratio and the nanoemulsion keeps clear and transparent during the dilute processes.UV-VIS method was established to determinate the content of ADHC innanoemulsion and the content was detected as78.70mg·mL^-1. The solubility was morethan1000times than that in water；Stability tests demonstrated that the nanoemulsionwas stable at the humidity of75%, and at the temperature of40℃、4℃and25℃for3months. Their contents and diameters also had no obvious change; On the basis ofresults of release test, the ADHC nanoemulsion was proved to be a sustained–releasepreparation.To sum up, the prepared ADHC nanoemulsion possesses good appearance, stablequality, function of sustained-release, and can enhancing the solubility of the ADHC inADHC nanoemulsion. Therefore, this method is anticipated to be a new preparationprotocol of ADHC.