Adjuvants to prolong the local anesthetic effects of coated microneedle products.

The objective of this study was to identify an adjuvant for anesthetics coated on microneedles to provide rapid onset and prolonged analgesic action with minimal skin tissue reaction. Aqueous lidocaine or prilocaine formulations with or without clonidine or the related analogs, guanfacine and apraclonidine, were dip-coated onto polymeric microneedles. The amount of lidocaine or prilocaine coated onto the microneedles was assessed by high performance liquid chromatography (HPLC). Delivery efficiency and dermal pharmacokinetics associated with lidocaine or prilocaine delivered via the microneedles were characterized in vivo using domestic swine. Skin punch biopsies were collected and analyzed to determine the anesthetic concentrations in the skin using HPLC-mass spectrometry (LC-MS). Addition of clonidine to the formulations decreased the systemic absorption rate of the anesthetics from the patch application site without impacting the coating performance or the rapid onset of anesthesia. Formulations with 0.3 wt.% clonidine, identified as the optimal dose for lidocaine-delivery via microneedles, maintained the lidocaine skin concentration above the estimated therapeutic level (100 ng/mg) for 1 h without causing any skin irritation or color change. The other two clonidine analogs, guanfacine and apraclonidine, also led to delayed systemic absorption of lidocaine from the skin, indicating utility in providing prolonged analgesia.