The Preparation Of Doxycycline Hydrochloride Sustained-release Pellets And The Release Model In Vitro

Doxycycline HCL is a semi-synthetic tetracycline broad-spectrum antibiotic,which has the advantages of small toxicity,good antibacterial activity and so on.It is used for infection of gram-positive bacteria,negative bacteria and mycoplasma.Doxycycline HCL is a time-dependent antibiotic,The longer the body stays in the body,the better it will be to use its antibacterial effect.However,doxycycline HCL is unstable in strong alkaline environment and aqueous solution,and it is easy to produce chemical reactions such as hydrolysis and oxidation when exposed to light and heat,this phenomenon reduces the usage of doxycycline HCL and seriously affects its clinical application.In order to improve the physical stability of hydrochloric acid,extending the duration of the drug,reducing the number of doses,lower the cost of medicine,adapting to clinical application,In this paper,the preparation of doxycycline hydrochloride sustained-release pellets was developed.We screening out the optimum composition and preparation process of the pellets by single factor test and orthogonal design test.It has been successfully prepared the sustained release pellets with good release effect and good formability,and the expected purpose was achieved.The main results are as follows:1.Ultraviolet spectrophotometry was used to determine the content of doxycycline in vitro,and according to the methodology test results,the method is simple,feasible,low cost,fast analysis,high sensitivity,good selectivity,accuracy and precision,which is suitable for the content determination of doxycycline in vitro.2.Taking the molding and dissolution of pellets as the indexes,the optimal prescription composition was 10%doxycycline,60%MCC101,10%SA,1%HPMC and19%starch,the optimal preparation process was 45 rpm/min extrusion speed,400 rpm/min rounding speed and rolling 5min.And three batches of pellets prepared according to the prescription and process have good reproducibility.3.The results of the study in vitro release showed that ordinary pellets had been released at about 5 min,and the sustained-release pellets were completely released at about1 h,in conclusion,the effect of sustained release was obviously improved.4.According to the results of the release study in vitro,we fitted the different pharmacokinetic models,and the release behavior of doxycycline sustained-release pellets conformed to the Weibull equation model,R~2 was 0.9897.