Formulation and evaluation of PVA-sucrose dissolving microneedles loaded with glimepiride nanocrystals as a potential transdermal delivery system

Abstract

Considering the limited research on microneedles for potent transdermal oral hypoglycemic drugs, in this study, we formulated, glimepiride nanocrystals and incorporated them into PVA-based, sucrose-dissolving microneedles. Nanocrystals were formulated using two different aqueous surfactant solutions as antisolvents, PVP (at concentrations of 0.2% w/v or 2.5% w/v) and SLS (0.2% w/v), with or without a post-drying grinding step. Glimepiride nanocrystals using 0.2% w/v SLS with grinding showed the smallest particle size of 348 ± 27 nm with a PI of 0.29 ± 0.05, which was confirmed by SEM imaging. Therefore, the SLS-with-grinding formula was used for incorporation into a polymeric microneedle formulation composed of 23% w/w PVA and 15% w/w sucrose (GLIM_MN). GLIM_MN showed a microneedle height of 500 ± 14 μm and a sharp tip, as shown under SEM imaging. Furthermore, GLIM_MN could withstand a force of 32 N for 30 seconds at a rate of 0.5 mm per second. Moreover, GLIM_MN successfully penetrated three layers of Parafilm, which is analogous to the mechanical properties of the skin, and successfully penetrated excised BALB/c mice skin to a depth of 480 ± 15 μm, as shown by bright-field image microscopy. Moreover, GLIM_MN showed full penetration of the array into excised human skin to a depth of 276 ± 65 μm. Subsequently, we monitored the glucose level in healthy BALB/c mice for over 24 hours. The GLIM_MN treated group showed a rapid decline in the blood glucose level, reaching a minimum level at 5 hours. This was also corroborated with an increase in the level of serum insulin in the GLIM_MN treated group compared with that in the untreated group 5 hours after administration. Moreover, GLIM_MN-treated mice showed no significant change in the serum C-reactive protein level compared with that in the untreated group, indicating no inflammation upon microneedle administration. These results collectively indicate that our glimepiride dissolving microneedle formulation can enhance the delivery of glimepiride with minimal invasiveness, causing no inflammation. Therefore, it can be considered a potential treatment in the management of type 2 diabetes mellitus, avoiding the drawbacks associated with conventional oral administration.