Preformulation Key Technologies Study On Novel Antiviral Drug GZ914

Virus is a non-cell morphology that incapacitated live independently without host cell.Most of infectious diseases are caused by virus,such as influenza,AIDS,smallpox,viral hepatitis and poliovirus,these diseases not only endanger human physical but mental condition.There are two main ways to solve the problem,vaccine injection and drug therapy,both of them are not imperfect.Vaccine incapable provide protection timely after the outbreak of the new virus,besides the incompleteness of new vaccine production platform,all they made vaccine production unable fast and generous,thence,just rely on vaccination means are not completely against viral disease.However,antiviral drugs,also has the problem of low bioavailability,resistance and more adverse reactions,seriously impact the treatment effect.It is necessary to discover novel,high efficiency and broad-spectrum antiviral drugs,so that we can fight against viral diseases more confidence.GZ914 is a novel compound with antiviral activity,which is rapidly transformed into its active metabolite GZ915 in vivo.Recent pharmacological studies found that GZ914 is expected to be a novel antiviral prodrug.Pharmaceutical prefromulation studies consist of physical,chemical,biological and other properties research of the drug before it is formulated,these preliminary experiments provide direction and protection for the preparation production and clinical trials.In this study,these are a great number key technology research conducted of GZ914 model drug,so the oral solid preparation design progress may be smooth.Firstly,the inherent properties of GZ914 were studied,including the appearance of raw materials,physical-chemical properties and residue experiments.GZ914 drug are light yellow powder with crystal structure,low water-solubility and solubility increases with the pH increases.Meanwhile,a well HPLC analysis method was established.Then,the single related substances of GZ914 were synthesized and identified.In vivo,GZ914 transform into active metabolite GZ915 rapidly,and then model drug also degraded during the procedure of synthesis,research,storage and transportation.These products can be divided into organic and inorganic impurities,organic impurities are known as related substances,which may be unknown structures or may be known structures.It is important to research related substances in the quality control of new chemical entities.Related substances researching,we usually conduct series experiments,which includes strong destruction experiment,active drug/excipient compatibility test,as well as the long-term experiment and accelerated experiment in later preparation study.Strong destruction experiment mainly to study the unstable factors of model drug,which follows the law of material conservation,it would be better 90% main component existed.The related substances study are especially significance to GZ914 because that it is a prodrug.How related substances generate,how much the proportion of GZ914 degraded,what the related substances it is and who made that the unstable factors take place,we must make an intensive study to settle these uncertainty problem.Finally,ascertain the moulding techniques of GZ914.Including the option of excipients and preliminary dissolution condition.