HPMC/PVP K90 Dissolving Microneedles Fabricated from 3D-Printed Master Molds: Impact on Microneedle Morphology, Mechanical Strength, and Topical Dissolving Property

Abstract

Three-dimensional (3D) printing can be used to fabricate custom microneedle (MN) patches instead of the conventional method. In this work, 3D-printed MN patches were utilized to fabricate a MN mold, and the mold was used to prepare dissolving MNs for topical lidocaine HCl (L) delivery through the skin. Topical creams usually take 1–2 h to induce an anesthetic effect, so the delivery of lidocaine HCl from dissolving MNs can allow for a therapeutic effect to be reached faster than with a topical cream. The dissolving-MN-patch-incorporated lidocaine HCl was constructed from hydroxypropyl methylcellulose (HPMC; H) and polyvinyl pyrrolidone (PVP K90; P) using centrifugation. Additionally, the morphology, mechanical property, skin insertion, dissolving behavior, drug-loading content, drug release of MNs and the chemical interactions among the compositions were also examined. H51P2-L, H501P2-L, and H901P2-L showed an acceptable needle appearance without bent tips or a broken structure, and they had a low % height change (<10%), including a high blue-dot percentage on the skin (>80%). These three formulations exhibited a drug-loading content approaching 100%. Importantly, the composition-dependent dissolving abilities of MNs were revealed. Containing the lowest amount of HPMC in its formulation, H901P2-L showed the fastest dissolving ability, which was related to the high amount of lidocaine HCl released through the skin. Moreover, the results of an FTIR analysis showed no chemical interactions among the two polymers and lidocaine HCl. As a result, HPMC/PVP K90 dissolving microneedles can be used to deliver lidocaine HCl through the skin, resulting in a faster onset of anesthetic action.

Determination of vat-photopolymerization parameters for microneedles fabrication and characterization of HPMC/PVP K90 dissolving microneedles utilizing 3D-printed mold

“…Computer-aided design (CAD) software is initially utilized to design the 3D model following by converting the 3D model to the standard triangulation language (STL) format, which is the standard and most frequently used format 1 . The designed model is then sliced into layers 2 before sending to a 3D printer, and each sliced layer is constructed by a 3D printer 1 , 3 initiating from the base layer and constructing a series of layers on top 2 . 3D printing plays an important role in object fabrication with a high complexity in a fast and efficient method 4 .…”

“…Although MEMS is an effective technology for micro-device fabrication because this technology has the potential for mass production of those micro-devices, it has complex muti-step of production, and requires specialize training, including high cost of the machine 5 . Thus, 3D printing can be utilized to fabricate 3D objects rather than MEMS since it can construct a high-resolution object in a fast production, including easy to scale up and unnecessary special training need 3 , 5 .…”

“…In vat-photopolymerization, a light-curable polymer resin is treated with either visible light or ultraviolet (UV) light initiating polymerization reaction, which the polymer chains are formed into a solid resin, which is irreversible and cannot be changed back to the liquid form 1 . Noteworthy, utilization of vat-photopolymerization techniques, such as stereolithography (SLA) and digital light processing (DLP) 2 has been reported for printing MN patch 3 because of a low cost of 3D printer and these two technologies give high resolution 3D objects. In DLP, digital light projector is used instead of a mirror, which is employed in SLA, to scatter a laser source accelerating the printing process 1 .…”

“…In DLP, digital light projector is used instead of a mirror, which is employed in SLA, to scatter a laser source accelerating the printing process 1 . Due to the same resolution of the object, utilization of SLA printers tends to be more affordable than DLP printers since SLA printers are cheaper than DLP printers 3 . At present, directly 3D-printed MN via vat photopolymerization shows some drawbacks, such as photo-absorber toxicity, and unable to incorporate drug during printing process 6 .…”

“…On the other word, drug-loaded MN can temporarily penetrate the stratum corneum improving skin permeability and subsequently enhance penetration efficiency of the drug for greater therapeutic effect 17 , 19 since the utilization of MN to deliver drugs can avoid first-pass metabolism occurring at liver 20 . Interestingly, MNs are well-known as a painless device because they penetrate through the epidermis layer but not deep into the dermis layer where the nociceptive fibers and blood vessels located 3 , 20 . However, MN can be utilized to deliver drugs or substances into the systemic circulation by directly leading the drugs to the upper dermis layer, so the drugs can directly jump into the systemic circulation without facing the skin barrier 21 .…”