Study On Temperature-sensitive In Situ Gel Drug Delivery System Of Doxycycline Hydrochloride Microspheres

Doxycycline hydrochloride is a second-generation semi-synthetic tetracycline antibiotic.It has been widely used in human and veterinary clinics because of its broadspectrum antibacterial advantages,and has become a hotspot in recent years.Due to its poor stability and other factors,the application of doxycycline hydrochloride has been limited.In order to improve the stability of doxycycline hydrochloride,enhance the compliance of patients,reduce the irritation of the drug and the number of times of administration,this paper conducted a study on the doxycycline hydrochloride microsphere temperature-sensitive in situ gel delivery system.First,doxycycline hydrochloride chitosan microspheres were prepared.In this paper,chitosan-doxycycline hydrochloride microspheres were prepared by emulsification and cross-linking,using sodium tripolyphosphate as the cross-linking agent,and glutaraldehyde as the curing agent.The experiment was designed by Design-Expert software.The concentration of chitosan,the mass of doxycycline hydrochloride in the system,the speed of rotation and the volume of the oil phase were considered as factors for analysis.Four factors and three levels were used for analysis,and the drug loading and encapsulation rate were used to evaluate the microsphere prescription.Visibleultraviolet spectrophotometer was used to measure the drug loading and encapsulation efficiency of the prepared microspheres.The results showed that the concentration of chitosan was 20.00 mg/m L,the mass of doxycycline hydrochloride in the system was 0.3 g,and the speed was 910 r/min,the liquid loading and encapsulation efficiency of liquid paraffin at 12 mL were 56.49% and 61.41%,which were significantly better than the results of other experimental groups.They were determined as the preparation of chitosan-doxycycline hydrochloride microspheres.Program.Secondly,the characteristics of doxycycline hydrochloride chitosan microspheres were characterized.In this paper,the size and dispersion of microspheres were observed by scanning electron microscopy.It was found that there was almost no adhesion between microspheres,and the appearance was approximately spherical.On this basis,the microspheres were characterized and analyzed by Fourier infrared spectrometer,TGA thermogravimetric analyzer,X-ray diffractometer and Raman spectrometer,proving that doxy hydrochloride passed The way of inclusion is wrapped inside by chitosan.Then,the microspheres were subjected to in vitro release,stability investigation and cytotoxicity experiments,and it was found that the doxycycline hydrochloridechitosan microspheres had a good release effect and had good storage stability in high temperature,high humidity and light environments.The cytotoxicity test showed that the microspheres had weak or little cytotoxicity.In summary,the microspheres have good appearance,stable structure,smooth release,safety and non-toxicity,and can be used in subsequent gel experiments.Finally,in this paper,poloxamer was used as a gelling agent,and hydroxypropyl methyl cellulose was used as a suspending agent.A temperature-sensitive in-situ gel was prepared by the cold-dissolving method.Design and optimization,using poloxamer-407,poloxamer-188,and hydroxypropylmethyl fiber doses as factors,using a three-factor three-level method for analysis,and using gel temperature as an evaluation index for optimization And the in vitro release of the loaded microsphere gel was investigated.The results showed that the temperature-sensitive in situ gel prepared by the best prescription released only 41% of the content in 24 hours.Effect.It can be seen that the temperaturesensitive in situ gel of doxycycline hydrochloride microspheres can well meet the requirements of sustained-release preparations,can improve drug stability and prolong drug action time,and will provide a theory for the selection of antibiotic drug formulation Guidance and reference.