Development Of Desloratadine Microemulsion In Situ Gel

The global industrialization has developed rapidly since the 21st century.With the increasing environmental pollution and the prevalence of social anxiety,the incidence of allergic rhinitis(AR)in children,adolescents,and middle-aged populations has been increased.At the same time,more and more studies have found that AR is also related to the formation of other diseases such as otitis media,sinusitis,airway infections and asthma,and it has became a common disease that cannot be ignored in daily life.Desloratadine is currently known as the third-generation antihistamine with the strongest ability to bind to the H1 receptor.Due to its good medicinal activity and efficacy,the required dose of desloratadine is relatively lower than other antihistamines.At present,the common dosage forms of the drug on the market mainly include syrups,tablets,and suspensions.However,the above oral dosage forms not only have side effects on the gastrointestinal tract,but also have the first pass effect on drugs.At the same time,eating food and gastric emptying also have bad influence on the efficacy of drugs.The desloratadine microemulsion in situ gel developed in this subject can overcome above shortcomings of the oral preparations.Meanwhile,there are no relevant research reports about it at domestic and foreign so far.Therefore it will increase the new dosage forms of desloratadine in the market.The microemulsion in situ gel drug delivery system is the combination of microemulsion and in situ gel.The microemulsion drug delivery system is relatively stable,and has good solubility for a variety of water-insoluble drugs,thus can solve the problem of poor solubility of desloratadine.At the same time,microemulsion can also improve the drug’s permeability and accelerate the absorption of drug in the mucosa,so that the drug could entry into the blood circulation quickly to reduce the waste of the drug and improve the bioavailability.The in-situ gel is a new type of gel matrix,which is characterized in that it can specifically transform from a liquid form to a semi-solid form when used on the affected area.Therefore,the gel could stay in the affected area for a long time and the drug in it can be fully released.At the same time,because of the simple operation and the good usage feeling of the gel,it can improve the medication effect and medication enjoyment of patients in the future.In this project,the best prescription of desloratadine microemulsion in situ gel and the synthesis process route were determined through the formulation screening and process optimization.And the specification of desloratadine microemulsion in situ gel(1.0 g:90 mg)was also determined by referring to the domestic desloratadine syrup(100 mL:50 mg).The methods for the determination of main drug and related substances in desloratadine microemulsion in situ gel was established and their methodology was verified.The method for determination of the drug in the in vitro release experiment of self-made gel was established and the methodology was verified.The physicochemical properties and initial stability of desloratadine microemulsion in situ gel were investigated.In addition,the effects on the maxillary mucosa and ciliary swingtime of frogs by self-made gel were investigated to test the toxicity on nasal mucosa.The guinea pig AR model was also established,and the medicinal efficacy of the gel was preliminarily investigated by observing various pharmacodynamic indexes of the AR model animals after administration of the self-made gel.