Prescription Optimization And Medicinal Research Of The Exenatide Phase Transition Microneedle Patch

Exenatide is first choice of treating type 2 diabetes,there are two kinds of dosage form in the market currently,one is Byetta which injected twice a day,another one is long-term sustained release microsphere formulations named Bydureon which injected once a week.Exenatide which provides a new method of treatment for the treatment of type 2 diabetes is the first FDA-approved glucagon-like peptide one(GLP-1)receptor agonist,provides a new method of treatment,compared with other drugs,exenatide has its unique advantages,including glucose dependent hypoglycemic effect,stimulate insulin secretion,suppress glucagon secretion,inhibit the apoptosis of pancreatic islet beta cells,reduce the gastric emptying,reduce appetite,etc.But exenatide has a short half-life,patients must inject many small doses to establish the tolerance of exenatide.Frequent injections caused inconvenience and pain to the patient.To solve those problems,this experiment aimed to study exenatide-loaded phase transition microneedle patch,which is safety and effective,convenient to use and establish tolerance,improve the compliance of patients.Exenatide-loaded phase transition microneedle was made by freezing at-20℃ for 12 h and thawing it at 4℃ for 4 h several time.The appearance of microneedle is uniform and smooth,microneedle was hard enough to insert skin epidermis layer under the conditions of dry,the microneedle can swelling to form drug release channel by absorbing fluids,drug moved to tissue and enter the bloodstream under the concentration difference thought the channel.This experiment studied the compatibility of PVA,HA/CMCNa,dextran-6000 and exenatide,the stability of exenatide in p H 7.4phosphate buffer,designed the prescription of microneedle,studied the effect of the excipients on the preparation process and drug release in vitro.The molecular weight of 400 k Da hyaluronic acid is prior to molecular weight of 4 k Da hyaluronic acid and carboxymethylcellulose sodium,the 24 hours cumulative release rate of microneedle with 400 k Da hyaluronic acid is about 90% in vitro.Finally,pharmacodynamics experiment through the type 2 diabetic rats,confirmed exenatide-loaded phase transition microneedle can reduce blood sugar.