Preparation Of Metformin Hydrochloride Sustained-release Microspheres

Microspheres technology is a new process and new technique,which has been mainly used in drug delivery system in the last 30 years.At present,the research on microsphere preparation mainly concentrates on the insoluble drugs,because there are many problems in the preparation of microspheres with water-soluble drugs.For example,the encapsulation efficiency,drug loading and the encapsulation yield are relatively low,and there are burst release phenomenon,which restricts the wide application of microsphere technology.The objective of this study was to prepare metformin hydrochloride sustained-release microspheres by W/O/W double emulsion method,and to improve the encapsulation yield of microspheres by adding gelatin to the inner water phase.We studied the various influencing factors on microspheres’ preparation,such as the technology factors and prescription factors.The microspheres were characterized by the particle size,encapsulation yield,and in-vitro drug release.The results of the optimized formulation of the microspheres were as follows:(1)Prescription: the concentration of drug is 10%;the concentration of gelatin is 20%;the concentration of ethyl cellulose is 10%;the oil phase solvent is dichloromethane saturated solution with metformin hydrochloric acid solution;the concentration of polyvinyl alcohol is 1%;both inner and external water phase solvents are water;the ratio of oil phase to inner water phase is 40:1;the ratio of colostrum to external water phase is 1:10;(2)Technology: the ultrasonic power: 300 W;pulse: 5 s/10 s;ultrasonic time: 25 s;emulsification time: 1 min;speed: 5000~8000 rpm(slow first and then fast).The quality of the microspheres was investigated,including the shape of microspheres,encapsulation efficiency,drug loading,encapsulation yield,the particle size distribution of microspheres and the drug release.The results showed that the microspheres are relatively uniform in size,spherical round and no adhesion,the average particle size is 126.9±2.35 μm,the average drug loading is 7.0±0.13%,the average encapsulation efficiency is 97.6±0.73%,and the average encapsulation yield is 81.4±0.66%.From the microsphere in vitro release test results,it can be seen that the amount of burst release of the prepared microspheres within the first 0.5 h is about 7.4%,less than 40%,and there is no obvious burst release effect.The release of the microspheres can last for 96 hours and the cumulative release rate is 82.4%.The stability test showed that there was no obvious change in the appearance,particle size,drug loading and encapsulation efficiency of the microspheres,indicating that the prepared microspheres had good stability.