Study On Oral Medicine Device Based On 3D Printing Technology

3D printing is a kind of rapid prototyping technology.It is a technology to generate three-dimensional entities by continuously adding materials layer by layer on the top of physical layers.In the past twenty years,3D printing technology has developed rapidly with the rise of technology in related disciplines.3D printing has made certain research progress in the field of pharmacy,especially in recent years.It is more suitable for the preparation of tablets and controlled release preparations by fused deposition method.Spritam,a 3D printed anti-epileptic drug approved by the FDA is available for patients with swallowing disorders at 2015.However,there are few researches on pharmaceutical products about the oral cavity based on 3D printing technology,such as 3D printing chewable tablets,which can improve the medication compliance of special people who have difficulty in medications such as children and the elderly.The route of administration and drug delivery devices for such special populations have been explored by researchers,and 3D printing is just a requirement for on-demand drug delivery.We combined the 3D printing technology to prepare oral medicine devices,and explored the properties,release mechanism and pharmacodynamics of the device.1.3D printed clonidine hydrochloride orthodontic retainerThe purpose of this study was to prepare a long-term sustained release oral clonidine hydrochloride tooth holder by 3D printing technology.Two kinds of good biocompatibility of material Poly(lactic acid)and poly(caprolactone)were the main components of orthodontic retainer,and clonidine hydrochloride was chosen as a model drug.It was mixed and molten with polyethylene glycol 4000.then mixed with two kinds of material and tween-80 to form a system.Finally mixed and molten the system by the desktop extruder to prepare the clonidine hydrochloride extruded filaments and printed orthodontic retainer.The vitro release experiments proved that there is a obvious burst effect of the original retainer,and the first day of release is much higher than the daily demand of clonidine hydrochloride.We tried to solve this problem through two processes.Firstly,the surface of the original retainer was coated with hydroxypropyl methicellulose and ethyl cellulose,and the burst effect showed no obvious improvement,so we remove the surface drug by soaking.Finally,clonidine hydrochloride orthodontic retainer prepared by soaking was selected as the best technology.The results of DTA and XRD analysis showed that the crystalline state of CH could maintain in the retainer and did not change its crystal form.The TGA graph showed that all the components in the retainer kept stable in the whole HME and 3D printing processes.Observed filaments surface and internal structure and different process retainers of surface and internal structure difference before and after drug release by scanning electron microscope,the result showed that sticky clonidine hydrochloride microparticles existed on the surface of original retainers,leading to burst release and after the release,drug microparticles disappears and there were some tiny holes in the surface and a corroded channel inside because of the dissolution of drug,so it is further verified that clonidine hydrochloride existed in the original crystal state in the retainer and released by the diffusion mechanism.The blood concentration of the clonidine hydrochloride tooth retainer was simulated by Gastroplus.The blood concentration of the soaking process was stable,and it could be continuously released for more than 3 days,and it was very similar to the effective blood concentration.Therefore,the drug-loaded tooth retainer treated by soaking technology can achieve the desired sustained release effect.2.Functional capsaicin candy prepared by 3D printing molds for thetreatment of oral ulcerThe purpose is to use 3D printing technology to prepare different forms of drug-containing functional candies for children and other special groups who have difficulty taking the medicine.Capsaicin,the main active ingredient of chili,was selected as the functional factor and the dose was set at 0.05%,and xylitol was more suitable as candy to replace substrate used in traditional confectionery.10% Poloxamer 188 were added as the cosolvent and osmotic promoter.The preparation of confectionery is perfusion method.Firstly,various forms of candy molds are printed through the way of light curing,and then the whole system in the molten state was perfused into the molds,and the molds are removed after cooling and solidification.It has been reported in relevant literature that capsaicin at a certain dose can promote healing besides analgesic and anti-inflammatory pharmacological effects.Therefore,animal experiments were conducted to explore.Firstly,a circular ulcer model with a diameter of 0.5 cm was established in the mouth of SD rats by phenol burn method.After 24 hours,the formation of gray pseudomembrane represented the success of modeling.For 7 consecutive days,rats in each group were photographed and recorded the area of ulcer,and their daily weight and food intake were also recorded.After 7 days,it was observed that the ulcer healing rate of the capsaicin group was higher compared with the model group and the blank group,while the ulcer condition of the positive group did not improve significantly due to some side effects.The related inflammatory factors TNF-α,IL-6 and WBC of capsaicin group were significantly lower than other groups.The structures of the epidermis and lamina propria were restored and the collagen fibers were clearly visible,without swelling.Therefore,capsaicin candies have a obvious effect on promoting healing and anti-inflammatory of oral ulcer.This study makes use of the unique advantages of 3D printing technology to achieve on-demand drug delivery to prepare drug devices,oral cavity was selected as the drug delivery site.And this study provided a new way of thinking to solve the clinical medicine demand of special population.