Study On Long-acting Sustained-release Microspheres Of Galantamine

Alzheimer’s disease(AD)has become a serious threat and a major challenge to the health of the elderly and the aging society,respectively.AD is a common,irreversible and degenerative neurological disease caused by a variety of reasons.The current treatment methods for AD can only improve the symptoms of patients,but cannot cure.Therefore,patients with AD need long-term medication.Galantamine is a first-line drug for the treatment of AD,and the current drug formulation requires daily medication.The characteristics of memory decline in patients with AD often lead to the phenomenon of missing or taking more drugs.Therefore,it is significant to develop new formulation of galantamine.Compared with other formulation,sustained-release injections can maintain the effective concentration of the drug for a longer period of time,prolong the effective action time of the drug,and reduce adverse reactions.Due to the reduced frequency,it can also increase the medication compliance of patients.In this study,we use galantamine as a model drug to carry out the preparation of its sustained-release microsphere injection.First,we conducted a systematic pre-prescription study on galantamine: prepared it into a poorly soluble salt to reduce the solubility;performed a series of characterization of the poorly soluble salt;investigated the influence of external environment such as p H,temperature and other factors on the stability of the poorly soluble salt;established a detection method for the content of the poorly soluble salt;Solubility of soluble salt in common organic solvents and dissolution media,oil-water partition coefficient,crystal form,etc.Secondly,we used the classic O/W emulsification-solvent volatilization method to prepare galantamine microspheres.The influence of dosage,type of excipients,composition,and concentration factors on the preparation of galantamine microspheres was investigated.And we compared and analyzed the appearance of the microspheres,the factors affecting the appearance of the microspheres,particle size and particle size distribution,drug loading,encapsulation efficiency and the distribution of drugs in the microspheres with different methods.The content of galantamine microspheres and the in vitro release of microspheres are determined by high performance liquid chromatography,which possessed the following characteristics:easy to operate,high precision and good accuracy.Finally,an in vitro evaluation method for galantamine microspheres was established.With this in vitro evaluation,we explored the impact of environmental factors,prescriptions,and technology on the release of microspheres;and explored the release mechanism and release rules of microspheres.The research results were summarized as following: prepare galantamine into a poorly soluble salt can reduce its solubility in water with a slow-release effect;p H bias and elevated temperature could reduce the stability of galantamine pamoate;Using O/W method to prepare galantamine microspheres can appropriately reduce the volume of the internal water phase and increase the concentration of excipients,and can also increase the drug loading of the microspheres;appropriately increase the concentration of the external water phase can increase the drug loading of the microspheres;The addition of emulsifier in the oil phase can increase the encapsulation efficiency of microspheres.This study finally established a simple process with controllable quality method for preparing galantamine microspheres with a drug loading amount of 30%,a release period of 2 to 4 weeks.