| Adrenaline is a hormone secreted by the adrenal medulla when stimulated by the outside world.It is very important to maintain the nerve excitement and heart beat of the human body.Adrenaline is also an essential drug for emergency rescue such as cardiac arrest,bleeding and shock.Firstly,the solubility of API at different p H was investigated.Through the investigation of saturated solubility and instantaneous solubility,it was found that the solubility of adrenaline gradually decreased with the increase of p H.according to the solubility and the p H range required for nasal spray,the specification of nasal spray was preliminarily determined as 5mg /ml;Secondly,through the study on the compatibility of raw and auxiliary materials,the stability of the preparation was preliminarily investigated.The results showed that the compatibility of raw and auxiliary materials was good;Through the investigation of the uniformity of each spray content of the two spray pumps,it is preliminarily determined that the pump head packaging material is VP7 model.Quality inspection and dosage screening of API and excipients;By adjusting the preparation to different p H,the stability of the preparation was investigated to determine the appropriate p H range.Through the investigation and screening of the adding sequence of raw and auxiliary materials,the material of production equipment,and the storage time of the drug solution,it is determined that the adding sequence of the prescription process is disodium edetate,sodium pyrosulfite,sodium chloride,citric acid,adrenaline,water constant volume,stainless steel solution preparation tank and medical silica gel tube can be used,and nylon 66 material can be used for the filter membrane;The compatibility of the packaging materials was investigated,and the brown medium borosilicate glass bottle was determined to be used,and the compatibility of the packaging materials was good.In order to control the quality of adrenaline nasal spray,an HPLC method was established for the content of adrenaline nasal spray,related substances and disodium edetate,and a detailed methodological validation was carried out.The results showed that the method was accurate and applicable.Through the influence factor test,acceleration and long-term test,it is determined that the product has good stability under the conditions of high temperature of 60℃and light(4500±500lux),and the impurities do not exceed the limit within 3 months of long-term acceleration,so it has good stability.Using the scanning electron microscope mucosal morphology and the time of cilia movement of bullfrog maxillary mucosa as the basis for toxicological study,it was investigated that adrenaline nasal spray and functional excipients had little irritation to the mucosa,and there was no obvious damage to the mucosal morphology.The relative movement percentage of cilia movement compared with normal saline showed that there was a little damage,but it was reversible and safe.Establish the liquid quality analysis method of this product,carry out the specificity verification,draw the standard curve,take SD rats as animal models,after intravenous injection and nasal spray,respectively,investigate the blood concentration,compare the pharmacokinetic parameters with the injection,and calculate the absolute bioavailability.In conclusion,the adrenaline nasal spray prepared in this study belongs to the class II improved innovative drug of chemical medicine.Its formulation process is reasonable and perfect.It is suitable for industrial mass production,with controllable stability,and the bioavailability is equivalent to that of the injection.It can be applied to the out of hospital drug treatment of patients with severe allergic reactions and asthma,improve the drug compliance of patients,and provide new drug choices for clinical medication. |
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