Simvastatin Loaded Dissolvable Microneedle Patches with Improved Pharmacokinetic Performance

载有辛伐他汀的可溶性微针贴剂,具有更优的药代动力学性能

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Abstract

Microneedle patches (MNPs) are one of the emerging approaches for drug delivery involving minimal invasion and improved skin penetration of macro- and micro-entities. Herein, we report dissolvable microneedle patches (dMNPs) as a novel tool for better systemic delivery of Simvastatin in the management of hypocholesteremia. Thiolated chitosan (TC), polyvinyl pyrolidone (PVP) and polyvinyl alcohol (PVA) were employed in the development of dMNPs. Developed patches were characterized through SEM, FTIR, DSC, TGA, PXRD, dissolution testing, tensile strength, elongation (%), skin irritation studies, moisture content and pharmacokinetic evaluation. dMNP F26 exhibited excellent tensile strength (9.85 MPa), penetration potential (~700 µm), moisture content (5.95%), elongation (35.54%) and Simvastatin release of 77.92%. Pharmacokinetic properties were also improved, i.e., C(max) 1.97 µg/mL, t(max) 9 h, MRT 19.9 h and AUC 46.24 µg·h/mL as compared to Simvastatin solution displaying C(max) 2.55 µg/mL, t(max) 3 h, MRT 5.91 h and AUC 14.20 µg·h/mL thus confirming higher and improved bioavailability. Kinetic modelling revealed zero order as the best fit model based on regression coefficient. Histopathological findings proved the biocompatibility of the developed dMNPs.

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