RESUMEN
Conventional transdermal drug patches have been on the market since 1997 but their applicability for drug delivery is limited: currently only nearly two dozen of molecules have been approved by the regulatory authorities for transdermal administration and have reached the market. The possibilities for drug delivery via the skin can be improved and expanded by using microneedle patch technologies. However, most microneedle patches focus on the delivery of low amounts of drugs that are generally very potent due to the small dimensions of the microneedle systems. In this study nanoporous microneedle arrays (npMNAs) were combined with a liquid drug reservoir. The parameters that influence the diffusion of memantine from the drug reservoir through the npMNAs in an acceptor solution were investigated. Based on these results a model was developed to predict the diffusion of low-molecular-weight drugs as a function of npMNA properties (i.e., backplate thickness and surface area) and reservoir properties (i.e., volume and drug concentration). This generated an in silico model to predict the release of low-molecular-weight drug from a drug reservoir through a microneedle array into receptor solution, showed a good correlation with the delivery of memantine in a preclinical minipig study. The drug release rates by the npMNAs can be tuned and allow for both zero and first order release kinetics. Summarizing, this work shows that the npMNA technology is a versatile drug delivery system. The npMNAs can be combined with a (seamlessly connected) external drug reservoir and this integrated drug delivery system can be used to deliver at least 9 mg of memantine over 72 h in a preclinical minipig study.