Insertion behaviour of microneedle (MN) arrays depends upon the mechanical properties of the skin and, MN geometry and distribution in an array. In addressing this issue, this paper studies MN array insertion mechanism into skin and provides a simple quantitative basis to relate the insertion force with distance between two MNs. The presented framework is based on drawing an analogy between a beam on an elastic foundation and mechanism of needle insertion, where insertion force is separated into different components. A theoretical analysis indicates that insertion force decreases as interspacing increases. For a specified skin type, insertion force decreased from 0.029 to 0.028 N/MN when interspacing at MN tip was increased from 50 μm (350 μm at MN base) to 150 μm (450 μm at MN base). However, dependence of insertion force seems to decrease as the interspacing is increased beyond 150 μm. To assess the validity of the proposed model, a series of experiments was carried out to determine the force required for skin insertion of MN. Experiments performed at insertion speed of 0.5 and 1.0 mm/s yielded insertion force values of 0.030 and 0.0216 N, respectively, for 30 μm interspacing at MN base (330 μm interspacing at tip) and 0.028 and 0.0214 N, respectively, for 600 μm interspacing at MN base (900 μm interspacing at tip). Results from theoretical analysis and finite element modelling agree well with experimental results, which show MN interspacing only begins to affect insertion force at low interspacing (<150 μm interspacing at MN base). This model provides a framework for optimising MN devices, and should aid development of suitable application method and determination of force for reliable insertion into skin. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1209–1221, 2013

Transdermal drug delivery using microneedles (MNs) depends on the rate of drug transport through the viable epidermis. Therefore, minimising the distance between the drug‐loaded surface and the microcirculation in the dermis where the drug is absorbed into the body is significant in improving drug delivery efficiency. A quantifiable relationship between MN design parameters and skin diffusion properties is therefore desirable, which is what this study aims to achieve. A framework is presented to quantitatively determine the effects of design parameters on drug diffusion through skin, where the effects of compressive strain on skin due to insertion of MN are considered. The model is then used to analyse scenarios of practical importance. For all scenarios analysed, predicted steady‐state flux was found to be lower when effect of MN strain on diffusion coefficient was accounted for. For example, simulations results indicated increasing tip radius from 5 to 20 µm and flux increased from 6.56 × 10⁻⁶ to 7.02 × 10⁻⁶ mol/(m² s) for constant diffusion coefficient. However, if the effect of strain on diffusion coefficient is considered, the calculated flux increases from 5.30 × 10⁻⁶ to a peak value of 5.32 × 10⁻⁶ mol/(m² s) (at 10 µm) and decreases to 5.29 × 10⁻⁶ mol/(m² s). This paper contributes by reporting a framework to relate MN geometry to permeability with inclusion of the possible effects the MN design may pose on the diffusion coefficient. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:164–175, 2012

In the last two decades, microneedles (MNs) have received significant interest due to their potential for painless transdermal drug delivery (TDD) and minimal skin damage. MNs have found applications in a range of research and development areas in drug delivery. They have been prepared using a variety of materials and fabrication techniques resulting in MN arrays with different dimensions, shapes, and geometries for delivery of a variety of drug molecules. These parameters play crucial roles in determining the drug release profiles from the MNs. Developing mathematical modelling, simulation, and optimisation techniques is vital to achieving the desired MN performances. These will then be helpful for pharmaceutical and biotechnological industries as well as professionals working in the field of regulatory affairs focusing on MN based TDD systems. This is because modelling has a great potential to reduce the financial and time cost of both the MNs’ studies and manufacturing. For example, a number of robust mathematical models for predicting the performance of the MNs in vivo have emerged recently which incorporate the roles of the structural and mechanical properties of the skin. In addressing these points, this review paper aims to highlight the current status of the MN modelling research, in particular, the modelling, simulation and optimisation of the systems for drug delivery. The theoretical basis for the simulation of MN enhanced diffusion is discussed within this paper. Thus, this review paper provides a better understanding of the modelling of the MN mediated drug delivery process.

This article reports on microneedles produced from biopolymer films extracted from fish scales of tilapia (Oreochromiss sp.) using micromolding technique. Evaluation of the properties of polypeptide films prepared from the fish scales gave refractive index (1.34), protein concentration (78%), ash content (1.6%) at (22%) moisture content. The microneedles successfully inserted into artificial skin models and imaging using digital camera showed microneedles remained intact when inserted and when removed from the skin model. Microneedles also successfully inserted into porcine skin and were shown to dissolve gradually at 0 s, 60 s, 120 s, and 180 s after insertion. Microneedles containing methylene blue as model drug were also produced and successfully pierced porcine skin. 3D finite element (FEM) simulations were performed using the measured mechanical properties of the biopolymer films (Young's modulus 0.23 N/mm² and tensile strength 1.8105 N/mm²) to evaluate the stress distribution on various dimensions of the fish scale derived microneedles and hence, their ability to withstand force necessary to pierce the skin without fracture. Results from mechanical analysis using FEM showed that microneedles with tip radius between 10 and 100 μm could withstand up to 0.12 N of force per microneedle without fracture, which is indicated when the stress at the tip of the microneedle exceeds the ultimate stress of the material of fabrication. Using skin insertion tests and finite element simulations, this study provides evidence that microneedles fabricated from fish scale biopolymer can effectively pierce and degrade into skin and therefore are good candidate for transdermal applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40377.

Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture.

Fish scale biopolymer blended with nanocellulose crystals is used for production of microneedles applying mechanical press microfabrication and the effect of nanocellulose on microfabrication, water absorption, moisture stability and mechanical properties of the microneedles is reported. The results show that microneedles produced from the nanocellulose loaded fish scale biopolymer requires higher temperature for micromolding (80 ± 5 °C) than microneedles from only fish scale biopolymer, which were moldable at 50 ± 5 °C. The mechanical properties of the fish scale biopolymer-nanocellulose (FSBP-NC) films showed that the addition of nanocellulose (NC) resulted in lower elongation and higher tensile stress compared to fish scale biopolymer (FSBP) films. The nanocellulose also prevented dissolution of the needles and absorbed up to 300% and 234% its own weight in water (8% and 12% w/w NC/FSBP), whereas FSBP films dissolved completely within 1 min, Indicating that the FSBP-NC films can be used to produce microneedles with prolonged dissolution rate. FTIR spectrometry of the FSBP films was compared with the FSBP-NC films and the NC gels. The FTIR showed typical peaks for fish scale polymer and nanocellulose with evidence of interactions. SEM micrographs showed relatively good dispersion of NC in FSBP at both NC contents corresponding to 8% and 12% w/w NC/FSBP respectively.