KJ Hansen, JK Simons, TA Peterson 3M’s hMTS provides intradermal delivery of relatively high volumes of liquid API formulations. Infusion time may be anywhere from 5-30 minutes depending on the volume and the physical/chemical characteristics of the formulation. In a human clinical trial, results indicate that hMTS can be applied – and a high volume infusion administered – with little or no discomfort to the patient. Visual evidence of the infusion disappears rapidly in most subjects. Results of in-vivo characterization of hMTS delivery indicate a safe and flexible delivery system. The hMTS can provide PK profiles and bioavailability measurements similar to those achieved via subcutaneous injection. Uptake of the drug by the systemic circulation may, in some cases, be faster than by injection. Under extreme force, 3M’s hMTS polymeric arrays bend, but not break, all but eliminating the risk of structure loss in the application site. Purpose. A polycarbonate array containing multiple hollow microstructures has been developed to enable rapid transdermal infusion of several non-traditional transdermal APIs. The utility of the hollow microstructured transdermal system (hMTS) has been tested in-vivo and in humans, demonstrating the potential of this delivery technology for relatively high volume injectables traditionally delivered by syringe. Methods. Using an external applicator, the hMTS array was inserted into tissue (human and animal) to allow intradermal infusion of several different liquid formulations. After infusion of active into domestic swine, blood samples were collected and assayed using liquid chromatography coupled to tandem mass spectrometry or to a UV detector or via ELISA. Back pressure was collected using an in-line pressure transducer. When tested in humans, subjects were asked to rate pain using a 10 point pain scale before, during and after infusion of a placebo. Results. Tested in domestic swine, the pharmacokinetic profiles resulting from intradermal infusion through the hMTS were comparable, with respect to Cmax and bioavailability, to those measured following subcutaneous injections. Up to 1mL of formulation has been infused, according to different infusion rate profiles, in less than fifteen minutes and up to nearly 40 minutes. When tested in humans, the infusions were completed with minimal discomfort and minimal irritation to the application/infusion site. The speed of delivery, the absolute bioavailability and the diversity of APIs achieved using the hMTS technology far exceed those achieved using existing (patch) transdermal technologies. Conclusions. Up to 1mL of liquid formulation can be infused in less than 15 minutes using plastic hollow microstructures with minimal discomfort and minimal site reactions. These results demonstrate the potential utility of hMTS to transdermally deliver a wide variety of formulations typically requiring injection, and to show pharmacokinetic performance similar to those resulting from high volume injections. The hMTS technology is compatible with a wide variety of water-soluble or partially water-soluble APIs. These characteristics provide faster, more complete, and more versatile delivery than can be achieved using existing passive (patch) transdermal technologies. These data show the distribution of the maximum infusion pain collected after or during infusion via hMTS of at least 0.75mL of placebo formulation. All applications were to the upper arm or the upper thigh, infusion time was between minutes. A naloxone formulation was administered to swine via 3M’s hollow microstructures according to several different infusion profiles or via subcutaneous injection. Sera samples were collected over 2 hours and analyzed via LCMS. Comparative results are shown below. A commercial hGH formulation was administered to swine via infusion through hollow microstructures or via subcutaneous injection. Sera samples were collected over 8 hours and analyzed via ELISA. Comparative results are shown below. Subjects were administered mL of placebo via a hMTS proof-of-concept device applied to the upper arm or upper thigh. The average pain score associated with the application of the microstructures was 1.4; the average pain score associated with infusions greater than 0.75mL was 1.8. Upon examination of the infusion site two hours after removal of the hMTS POC patch, 48% of infusion sites evidenced no visual vestiges of the infusion. At 36 hours post-infusion, 89% percent of infusion sites had no visible vestige of the infusion; the remaining 11% of infusion sites were scored “minimal erythema, barely perceptible” by the attending physician. hMTS leverages 3M expertise in drug delivery, pharmaceutical development, microreplication, surface coating and manufacturing process optimization. Liquid drug formulations of µL were administered to swine using an hMTS integrated device or a proof-of-concept device. Hollow microstructures were applied such that the infusion depth ranged from µm beneath the surface of the skin. For comparison, the same concentration and volume of liquid formulation was administered via subcutaneous injection. Blood samples were collected after dosing and assayed using either LCMS or ELISA. Various infusion parameters were utilized in the delivery of naloxone, causing variations in the results PK profiles. Following hMTS infusions greater than 750µL, a small bleb may be observed on the surface of the skin but dissipates complete in less than an hour. 3M Drug Delivery Systems Transdermal delivery of high volume liquid formulations using hollow microstructures Array Performance 3M Molding and Microreplication Capabilities Summary of POC Study in Humans – preliminary results hMTS for Delivery of High Volume Liquid Formulations IntroductionFormulation Compatibility Distribution of Max Pain Scores associated with hMTS Infusion, mL Placebo PK profiles for Naloxone Administered with Different Infusion Parameters Summary of hMTS Infusion POC Study in Humans Comparative PK profiles for hGH Pharmacokinetics: hMTS Delivery of hGH Pharmacokinetics: hMTS Delivery of Naloxone Formulation compatibility studies are underway with respect to parameters such as viscosity, osmolarity, pH, API size, and the presence or absence of several common formulation components. A commercial naloxone formulation was administered to swine via infusion through hollow microstructures or via subcutaneous injection. Sera samples were collected over 8 hours and analyzed via LCMS. Comparative results are shown below. These paired images were taken before and after the microstructures were exposed to 245N of force administered against a hard substrate. The hMTS arrays are made of Class VI polymeric material and bend, but do not break when exposed to extreme force. The use of 3M’s hMTS with existing subcutaneous formulations and formulation components is being explored.