Study On Loratadine-sensitive Nasal Gel

Loratadine is a derivative of atazatadine,a long-acting tricyclic antihistamine.It has a good effect on allergic rhinitis,chronic urticaria,eczema,contact dermatitis and other allergic skin diseases,of which anti-allergy is most noticeable.In recent years,the research on the application of Loratadine to anti-allergy has increasingly attracted the interest of some researchers.However,since loratadine is hardly dissolved in water,the effective utilization rate is low,and the adverse reactions of the gastrointestinal tract and the damage of the liver function are easily generated by the oral administration method,which limit its clinical application.In order to solve the problem that loratadine is insoluble in water and its effective utilization rate is low,we have made it into an inclusion compound with 2-hydroxypropyl-?-cyclodextrin,which is the most widely used at present and it has the best effect for drug solubitization and stability enhancement.For the sake of relieving its adverse effects on the human body,we have avoided oral administration and use nasal administration.Thermo-sensitive gels are popular with patients because of their advantages such as ease of using,good compliance,safety and high efficiency.This topic applies the in-situ gel technology and prepares the clathrates as a temperature-sensitive gel for nasal administration for the treatment of rhinitis.It can not only exert the good anti-allergic properties of loratadine,but also prolong the residence time in the nasal cavity,and the blood drug concentration is stable.This can increase the safety of loratadine administration and reduce the risk of poisoning.We will mainly focus on the preparation process of loratadine inclusion compound,screening of gel matrix,preparation and quality inspection of temperature-sensitive gel,toxicity and irritation of nasal mucosa.The full text of the research includes the following aspects:(1)Firstly,the inclusion complex was prepared by the saturated aqueous solution method,and then the ultraviolet spectrophotometric method was used to detect the drug content of the inclusion complex.The influencing factors were selected by single factor experiment:molar ratio,inclusion temperature and inclusion time.The best process was obtained:the molar ratio was 1:1,the temperature was 60°C,the inclusion time was5 hours,the average drug loading measured by the parallel test was17.75%,and the RSD%was 1.12%.Differential scanning calorimetry was used to identify whether the inclusion compound was successfully prepared.(2)For the screening of gel matrix,this article mainly focused on the gelation temperature,gel adhesion and cumulative release in vitro as the reference standard.The main matrix prescription was 18%P407,4%P188,0.2%Carbopol 934.After the measurement,the gelation temperature was 32.7±0.5°C,the adhesion force was 2668 mPa·s,and the release degree was 80.02%.The indicators of the matrix all met the reference standards.(3)When the quality of the gel was examined,the viscosity,cumulative release in vitro,pH value,and gel strength of the preparation were mainly investigated.The results of the tests all met the corresponding requirements;The specific test,precision test,stability test,and repeatability test of the thermosensitive gelling agent by the UV spectrophotometry all indicate that the method is good.The R~2 of the obtained standard curve is equal to 0.9998,indicating that the linear relationship is good.Through the high temperature test,high light test,and accelerated test,the color of the gel did not change significantly,the content of loratadine changed within a reasonable range,and the stability of the preparation was good.(4)The chick embryo allantoic membrane and New Zealand white rabbits were used as experimental models to establish chicken embryo allantoic membrane experiment and skin irritation experiment to initially evaluate the safety of the gel.In the chorioallantoic membrane experiments,neither the blank gel nor the administered gel caused hemorrhage,coagulation,and hemolysis in the chicken embryo allantoic membrane,indicating that the gel preparation had no biofilm toxicity;in skin irritation During the sexual test,no response to erythema or edema on the local skin of the experimental white rabbit was observed using blanks and gel administration.The results indicated that there was no skin irritation during the administration of loratadine thermosensitive gel.It further proves the safety of the gel.