Research Of A Novel Drug Loading Liquid Crystal Gel System

As a kind of drug delivery agents,drug carrier can protect drugs and make them be absorbed by human body,meanwhile it can achieve the aim of drug targeting delivery and control the release rate.With the development of science and technology,many new formulations were developed,and study of drug carrier such as microemulsion,submicroemulsion,liposome,alcohol liposomes,microspheres,nano materials and gel have been made significant progress.As a novel drug carrier,lyotropic liquid crystals(LLCs)has been paid attention to.As drug carrier,lyotropic liquid crystals can improve the stability of drugs and prevent the enzymatic hydrolysis of protein,peptides and other bioactive molecules,and it can realize the sustained-release of drugs in body,thereby reducing the time of administration,bring great convenience to the patients.Gastroenteropancreatic endocrine tumors(GEP-NETs)is caused by the neuroendocrine cell in the stomach,intestines and pancreas under the action of carcinogenic factors.Drug therapy can relieve the disease symptom caused by tumor,inhibit tumor growth,control the primary tumor metastasis to the surrounding areas and has a good effect for the mitigation and treatment of GEP-NETs.Octreotide acetate is one of the commonly used drugs in the treatment of these kind of tumors.Octreotide acetate(OA)is a somatostatin analogue,which can combine somatostatin receptor in stomach,intestine and pancreas,and inhibit the excessive secretion of various hormones in these areas.Stopping the drug will not cause a rebound phenomenon of hormone secretion.At present,The main form of available octreotide acetate is injection type,and it often given by the method of subcutaneous injection and intravenous drip.But the drug has a short half-life in vivo,and frequent dosing is required,so it will brought inconvenience and pain to patients and cause economic burden to them.In order to prolong the action time of medicine in the administration site,increase its bioavailability and reduce the number of medication,this project intends to develop a kind precursor formulation of octreotide acetate liquid crystal which has the slow release effect of drugs,and the gelling reaction will occur when encounter water.The preparation Include soya phosphatidyl choline(SPC)and glycerol dioleate(GDO),which are natural materials and have good biocompatibility.Through the single factor experiment,this study investigate the effect of ethanol dosage and the ratio of SPC and GDO on the properties of octreotide acetate liquid crystal gel precursor.The ethanol dosage is 15wt%,which is determined by the appearance and performance of forming system.By investigate the gelling ability,needle penetration properties and rheological properties of the system,the quality ratio of SPC and GDO is choosed preliminary,which is between 70:30 and 30:70.Optimization of the octreotide acetate formulation is complete by characterize the liquid crystal structure of the system by cross-polarizing light microscopy and investigate release properties of different systems in vitro,and the final quality ratio of SPC and GDO is 7:3(wt/wt).The octreotide acetate liquid crystal gel precursor after prescription optimization is light yellow,clear and transparent liquid,and it has good fluidity and injection performance in the storage condition.After subcutaneous injection into the body,it will form gelatinous semi-solid after contact with body fluids,thereby delaying drug release.The determination result of rotary rheometer show that the complex viscosity(?*)values of the formulation have significant difference before and after water is added.Under the condition of shear stress is 20 Pa and frequency is 0.1Hz,the ?* values of the precursor formulation is only 9.86×10-2 Pas,and the ?* values water of the formulation can reach 6.22×103 Pas after water is added,the result show that the formulation will has good adhesion in vivo.The quality control methods of octreotide acetate liquid crystal gel precursor is established,and drug content in preparation is determinate by HPLC.The specificity,precision,reproducibility,recovery rate of the method is inspection,and the rusult of the examination show that the method of HPLC is specific,and it has good precision and stability.The drug content measured by this method in the sample is in accordance with the regulations.The influence factors test showed that temperature and light have relatively great effect on octreotide acetate liquid crystal gel precursor,therefore the formulation should be kept refrigerated in the condition avoid light.At the same time,in order to avoid the subtle influence of water in the air on the formulation,the formulation can be stored in a dry environment,so that the formulation will have better stability.This study investigate the appearance and the content of the drug in octreotide acetate liquid crystal gel precursor by influence factors test and long-term stability test,so as to investigate the influence of different factors on the stability of formulation.The experimental results show that light and temperature have great influence on the stability of octreotide acetate liquid crystal gel precursor.Combine the result with the nature of itself,the formulation should be be sealed and stored in cold and dry storage environment and avoid light.In summary,the octreotide acetate liquid crystal gel precursor has good injection performance in the study.The stable gel structure is formed after administration by subcutaneous injection,and it have good drug sustained-release properties.