| As an alternative new drug delivery method to hypodermic syringe and transdermal patch,microneedle arrays could be used to permit the transport of macromolecules and offer a number of advantages for the patient,i.e.minimally invasive and pain-free treatment,ease of use for non-skilled,reduced risk of needle-stick injury.Polymer microneedle arrays are expected to become one of most important transdermal drug delivery methods because of their excellent biocompatibility,biodegradability,low cost and easy-to-batch production.Although the micro hot embossing based on mold was characterized by low process cost,simplicity in process and high precision,the process used to prepare microneedle arrays needs to be optimized.Taking polymer microneedle arrays as the studying object,this thesis focused on structural and system design for microneedle arrays and micro hot embossing process used to be prepare microneedle arrays.The main research contents were as follows:(1)Combining with human skin structure,and taking into account the characteristics of microneedle piercing into skin,both conical solid and hollow microneedle arrays were designed,the height is 550μm,tip diameter was 50μm,bottom diameter was 250μm and hollow microneedle’ channel diameter was 30μm.The stress analysis and strength checking of the designed microneedles were carried out to verify the theoretical reliability of the two microneedle arrays.In addition,two hollow microneedles drug delivery systems were designed.(2)The numerical simulation of micro hot embossing filling process for microneedles was carried out by DEFORM 2D.The simulation results showed that the non-closed micro hot embossing will have obvious edge effect,the flow barrier structure can weaken the edge effect,and the maximum accordance ratio can be increased by 22.1%.Under the conditions of specific molding temperature and embossing force,the rate of polymer filling decreased gradually with the embossing time until it tends to zero.Within the range of the process to be studied,the greater molding temperature or embossing force,the greater the filling height of the microneedle mold cavity.(3)Experimental study on the preparation of polymer microneedle arrays by micro hot embossing was carried out.The experimental results showed that the higher molding temperature or embossing force,the higher the microneedles height within the range of the process being studied.The effect of molding temperature and embossing force on microneedles height was consistent with the simulation results.The optimal parameters of molding temperature and embossing force were 120℃ and12.78MPa,or 124℃and 10.00MPa,or 124℃and 12.78MPa for achieving design height of PMMA microneedles.For PLA microneedles,the process conditions for achieving more than 0.5mm microneedles in height were T≥120℃ and P≥16.75MPa,where T is molding temperature and P is embossing force.The micro hot embossing auxiliary device not only can weaken the edge effect,but also can improve efficiency of the micro hot embossing process.As a result,the micro hot embossing cycle was shortened by 10-20 minutes.(4)The experiment was carried out on the effect of promoting permeation after insertion of microneedles into porcine skin.The results showed that the porcine skin treated with microneedles had a greater rate of transepidermal water loss than untreated porcine skin,and the difference of them in water content,at the beginning of the experiment was less than 1%,increased to 9.6%when the experiment was conducted two hours.Piercing the porcine skin,thicker than the human skin,when the pressure is applied to 60N,the microneedle array remained intact,which indicating that the microneedle arrays can be safely and effectively applied to human skin transdermal administration. |
PDF Full Text Request