Preparation And Property Characterization Of Dissolving Microneedles

Objective: The type of polymers can affect the formability and mechanical strength of microneedles(MN),as well as the delivery efficiency of the drug product.It is necessary to study the performance of MN with different polymers to overcome the limitation of MN that was prepared by using single type of polymer.Nicotinamide was selected as model drug,the property of microneedle prepared by new composite materials were verified.We developed nicotinamide dissolving microneedles that had clinical value,good formulation properties and drug delivery efficiency.Methods: MNs were fabricated from PVM/MA(Gantrez S-97),PMVE/MAH(Gantrez AN139),PVP K29/32,PVP K90,PVA 05-88 and HPMC E5,using the centrifugal molding method.The needle formability,needle content,insertion ratio and dissolution rate were evaluated to compare the performance’s difference of MN made by different polymers’ combination.Combined with texture analyzer and Parafilm insertion to verify the mechanical property of the better formulations Then,nicotinamide was selected as a model drug,PVP K29/32 and PVA 05-88 were used as new composite materials.The 1%,3% and 5% nicotinamide loaded DMNs were successfully formulated with combination of PVP K29/32 and PVA 05-88.Through H&E slices,texture analyzer,combined with Parafilm insertion,various performances of drug loaded microneedles were comprehensively evaluated,as well as the penetration depth of microneedles during skin penetration.Besides,to assess drug delivery efficiency,the amount of drug deposited in skin was measured.Results: The properties of MNs can be improved by combined ductile materials(PVA,HPMC)and brittle materials(Gantrez S-97,Gantrez AN139 and PVP K29/32).The formability and mechanical strength of MNs were significantly enhanced by adding more brittle materials.Microneedles was fabricated from PVA had good morphology,but the microneedle patch cannot be successfully penetrated the skin.It was shown that the microneedles fabricated from PVP K29/32 and PVA with various mass ratios(PVP K29/32: PVA)of 1:1～2:1,with the increase of the proportion of PVP K29/32,the mechanical strength of the needle was improved,and the addition of PVA significantly improved the toughness of PVP K29/32.When PVA was combined with PVM/MA,the greater the proportion of PVM/MA,the higher the insertion rate of microneedles.The ration of PVM/MA: PVA increased from 1:1 to 5:1,the insertion rate of microneedles increased from 66% to 100%.We found that the failure of PVM/MA:PVA(5:1)microneedles occurred when the compression force per needle exceeded 0.19 N.When PVA was combined with PMVE/MAH,the insertion rate for PMVE/MAH/PVA microneedles with mass ratios of 1:1 and 5:1 was 100%.Meanwhile,the compression forces for PMVE/MAH:PVA microneedles with mass ratios of 1:1 and5:1 were 0.20 N and 0.24 N,respectively.Different from PVA,the HPMC E5 microneedles had poor morphology.The morphology and mechanical strength for PMVE/MAH and HPMC E5 microneedle with rations of 5:1 was good,and the insertion rate of microneedles was 99%,the fracture force was 0.19 N.In this study,PVP with different molecular weights was also compounded.With the increase of the proportion of K90,the brittleness of K29/32 was significantly reduced.When the proportion of PVP K29/32 and K90 was 1:1,the insertion rate of microneedles was 100%.The compression forces for microneedles was 0.19N/needle.Besides,optimized combination of different polymers can promote the dissolution rate of MNs.In this study,nicotinamide was selected as a model drug,and PVA 05-88 and PVP K29/32 were used as new composite matrix materials.The nicotinamide loaded DMNs possess good formability,uniform drug distribution and excellent mechanical strength to penetrate into the skin.The results of histological sections showed that the microneedles could successfully pierce the stratum corneum and deliver the drug subcutaneously.The dissolution of DMNs was approximately 10 min.The amount of1%,3% and 5% nicotinamide loaded DMNs delivered in skin was 0.46±0.13%,1.55±0.38% and 3.32±0.69% after 1min respectively,which achieved drug delivery efficiently.Conclusion: These results indicated the microneedles with appropriate ratio of ductile and brittle materials possess good formability,excellent mechanical strength and good skin adhesion.In this study,new composite materials were selected to construct nicotinamide dissolving microneedles with different drug loading capacity,which have good morphology,mechanical properties and rapid drug release,and are expected to provide new methods and means for acne treatment,skin whitening and skin brightening.