Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force

Davis, Shawn P.; Landis, Benjamin J.; Adams, Zachary; Allen, Mark G.; Prausnitz, Mark R.

doi:10.1016/j.jbiomech.2003.12.010

Cited by 708 publications

(466 citation statements)

References 29 publications

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“…The force required to press the cylinder against the skin was recorded over time. A sudden drop in the force was taken as an indication that the stratum corneum had fractured, consistent with previous findings (Davis et al, 2004). The modified TMA procedure used here involved heating skin and then testing mechanical strength afterwards (at room temperature).…”

Section: Dsc Tga and Modified Tma Analysis Of Stratum Corneumsupporting

confidence: 75%

The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

111

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a b s t r a c tAlthough the effects of long exposure ( 1 s) to moderate temperatures (≤100 • C) have been well characterized, recent studies suggest that shorter exposure (<1 s) to higher temperatures (>100 • C) can dramatically increase skin permeability. Previous studies suggest that by keeping exposures short, thermal damage can be localized to the stratum corneum without damaging deeper tissue. Initial clinical trials have progressed to Phase II (see http://clinicaltrials.gov), which indicates the procedure can be safe. Because the effect of heating under these conditions has received little systematic or mechanistic study, we heated full-thickness skin, epidermis and stratum corneum samples from human and porcine cadavers to temperatures ranging from 100 to 315 • C for times ranging from 100 ms to 5 s. Tissue samples were analyzed using skin permeability measurements, differential scanning calorimetry, thermomechanical analysis, thermal gravimetric analysis, brightfield and confocal microscopy, and histology. Skin permeability was shown to be a very strong function of temperature and a less strong function of the duration of heating. At optimal conditions used in this study, transdermal delivery of calcein was increased up to 760-fold by rapidly heating the skin at high temperature. More specifically, skin permeability was increased (I) by a few fold after heating to approximately 100-150 • C, (II) by one to two orders of magnitude after heating to approximately 150-250 • C and (III) by three orders of magnitude after heating above 300 • C. These permeability changes were attributed to (I) disordering of stratum corneum lipid structure, (II) disruption of stratum corneum keratin network structure and (III) decomposition and vaporization of keratin to create micron-scale holes in the stratum corneum, respectively. We conclude that heating the skin with short, high temperature pulses can increase skin permeability by orders of magnitude due to structural disruption and removal of stratum corneum.

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Section: Dsc Tga and Modified Tma Analysis Of Stratum Corneumsupporting

confidence: 75%

The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

111

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“…Davis et al (2004) found that the force of microneedle fracture depends on the microneedle thickness. They noticed that the margin of safety (i.e., ratio between microneedle fracture and skin insertion force) reached its highest value with large microneedle thickness.…”

mentioning

confidence: 99%

Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability

Davidson

Al-Qallaf

Das

2008

Chemical Engineering Research and Design

144

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can potentially allow the transdermal delivery of many medicaments including large macromolecules that typically cannot diffuse through the skin. This paper addresses the use of microneedles coated with a drug solution film. In particular, we identify how the geometries of various microneedles affect the drug permeability in skin. Effective skin permeability is calculated for a range of microneedle shapes and dimensions in order to identify the most 20 efficient geometry. To calculate effective permeability (P eff ), the effective skin thickness (H eff ) is calculated. These are then plotted for insulin as a model drug to see how various microneedle parameters affect the profiles of both H eff and P eff . It is found that the depth of penetration from the microneedle array is the most important factor in determining P eff , followed by the microneedle spacings. Other parameters such as microneedle diameter and 25 coating depth are less significant.

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“…[ 43] From Figure 8, the maximum insulin concentration in blood of insulin was 0.31 ng/ml. Apart from the centre-to-centre spacing, the other dimensions have been kept constant as shown in 345 Table 1.…”

mentioning

confidence: 99%

Transdermal drug delivery by coated microneedles: geometry effects on drug concentration in blood

Al-Qallaf

Das

Davidson

2009

Asia-Pacific J Chem Eng

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Drug administration through transdermal delivery is restricted by the top layer of skin, the stratum corneum. One possible solution to overcome the barrier function of the stratum corneum is to employ microneedle arrays. However, detailed theoretical models relating drug‐coated microneedles and their geometry to the drug concentration in the blood are limited. This article aims to address this issue by examining the blood concentration profiles for a model drug, insulin, that has been administered via coated microneedles. A mathematical model is introduced and applied to predict theoretical blood concentrations. Furthermore, the insulin concentration in blood is calculated for a range of different microneedle shapes and dimensions to identify the most effective geometry. The results indicate that the optimum microneedle geometry in terms of maximizing insulin concentration was a rocket‐shaped needle with a constant tip angle of 90°. Also, it has been found that the number of microneedles in an array is the most significant factor in determining maximum insulin concentration in the blood (Cb, max). Penetration depth of the microneedle, centre‐to‐centre spacing and microneedle thickness had a less significant effect on the maximum insulin concentration in the blood. It is envisaged that the current study will help in designing microneedles of optimum size and shape for transdermal drug delivery. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.

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Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force

Cited by 708 publications

References 29 publications

The effect of heat on skin permeability

The effect of heat on skin permeability

Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability

Transdermal drug delivery by coated microneedles: geometry effects on drug concentration in blood

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