Construction Of Double-layer Microneedles Of Gum Arabic And Sumatriptan Delivery

Transdermal preparations are the third largest topical preparations after oral and injection,but the stratum corneum of the skin is rich in lipids,which limits the permeability of ionic and polar macromolecular drugs and has low bioavailability.The transdermal drug delivery formed by the microneedle array can successfully pass through the skin’s main barrier（the stratum corneum）,forming dense micropores in the epidermis,allowing drug molecules to flow into the dermis rich in capillaries,and effectively delivering drug macromolecules or active ingredients.The whole body circulates,does not touch the nerve fibers of the dermis,and has the characteristics of painless,minimally invasive or non-invasive.In this paper,using gum arabic as the main matrix,two dissolving microneedles with different drug release behaviors were constructed,and their performance and drug release behavior were studied.The main content is the following two parts:（1）During the acute attack of migraine patients,the self-treatment dose of drugs can alleviate the pain in time.In order to make the active drugs embedded in the transdermal preparation take effect in the shortest time,acacia gum with excellent solubility is selected as the matrix,because a single polymer has poor film-forming properties and high brittleness,and cannot be directly used to prepare microneedles.In this study,the insoluble composite formed by the crosslinking of hyperbranched gum arabic natural polymer by Ca²⁺was used as the framework material,and the preparation has good mechanical properties,solubility,and Sumatriptan double-layer microneedle patch with high drug loading.The puncture experiment showed that the microneedle can puncture the aluminum foil paper with the thickness of the human skin stratum corneum（15μm）without deformation,and the vertical application of5N/patch force can smoothly puncture the isolated pig skin;the drug load is 0.51mg（280needles/0.38cm²）The release of microneedle patch in vitro shows that compared with previous studies,the release rate of sumatriptan can be as high as 100%in 240s.The fitting results of in vitro release kinetics studies all show that matrix erosion is considered to be the drug release mechanism of sumatriptan microneedles.Taking 6mg of sumatriptan subcutaneously as a reference（approved by the US FDA）,the prepared microneedles with an area of 4.5cm²can meet the needs of administration.（2）In order to increase the application range of gum arabic and realize the slow release of sumatriptan,N-isopropylacrylamide（NIPAM）is used as the monomer,ammonium persulfate（APS）and sodium bisulfite（SBS）as the redox initiation system,and N,N’methylenebisacrylamide（BIS）as the cross-linker Coupling agent,a hydrophilic thermosensitive gel（GA-NIPAM）was prepared.Based on the analysis and characterization of infrared spectroscopy（FTIR）,X-ray photoelectron spectroscopy（XPS）and differential scanning calorimetry（DSC）,the morphological characterization,hardness test,solubility study and in vitro release of isolated pig skin of the GA double-layer microneedle patch were further discussed.Experiments showed that the gel LCST increased from 32°C to 37°C.As the proportion of gum arabic monomer increases,the LCST moves in the direction of increasing temperature,and the microneedles have good temperature responsiveness within the phase change range.The double-layer microneedles made of 30%wt GA-NIPAM polymer at room temperature have sufficient mechanical strength to penetrate the stratum corneum of pig skin,and the needle body can be completely dissolved within 30 minutes;p H=7.4phosphate at 20-40°C In the buffer medium,the GA-NIPAM microneedle patch loaded with rhodamine shows different drug release capabilities due to temperature sensitivity.The in vitro transdermal test results showed that the cumulative drug release and permeation flux of the microneedle puncture group were 6.383 times and 6.061 times that of the non-microneedle puncture group（control group）.The cumulative release of sumatriptan at 36hours was 4901μg,the delivery rate is 136.0±24.36μg/cm²/h,and it can be released continuously for a long time.