uPRAX Microsolutions

At uPRAX microsolutions we believe it is important to apply microneedles in an efficient and reproducible manner onto the skin to make microneedle-based drug delivery into a success. Therefore, we have developed a device to help universities, research institutes and companies that develop microneedles to optimize microneedle insertion into skin.

ABOUT US

uPRAX Microsolutions is a Dutch technology company founded in 2016 that is developing devices to apply dermal drug delivery systems and/or sampling devices (e.g., microneedles or microneedle arrays (medical devices)) on a controlled manner onto the skin. We believe it is important to apply microneedles on an efficient and reproducible manner onto the skin to make microneedle-based drug delivery (in a clinical setting) into a success. With our technology we offer a large flexibility regarding different types of microneedles of which the optimal insertion parameters need to be investigated as well as microneedle insertion optimization. Furthermore, we can customize our device for specific microneedles types/geometries according to the requirements of our customers. We further aim to develop standard methods and devices for microneedle insertion testing for regulatory purposes.

BACKGROUND

Introduction

Microneedles are needle like structures with a size of less than 1 mm that are used to deliver a drug into the skin and/or sample biological fluids from the skin on a minimally invasive and potentially pain-free manner. Microneedles currently receive a lot attention from both academia and (pharmaceutical) industry. Depending on the type of microneedle and type of drug to be delivered into the skin, microneedles as a drug delivery system have a huge potential as an alternative to oral and parenteral drug delivery. As exemplified below in figure 1, several types of microneedle technologies have been developed for dermal and transdermal drug delivery, including hollow microneedles, solid/coated microneedles, and dissolving microneedles. These different microneedles have been made with many different geometries (e.g., length, sharpness, diameter, density) and are made of several different materials (e.g., glass, silicon, stainless steel, titanium, sugar), which all influence the skin penetrating ability of microneedles. There is one common factor for all different types of microneedles: they must pierce the stratum corneum in order to deliver a drug into the skin.

Figure 1 Illustrations of dermal drug delivery by different types of microneedle technologies (adapted from: K. van der Maaden et al., Drug Deliv. and Transl. Res. (2015)).

Microneedle application

For a microneedle-based clinical end product obviously the application of microneedles should lead to a reproducible delivery of a drug. Therefore, microneedles should be reproducibly inserted into the skin. However, to achieve this most microneedle technologies require insertion devices as illustrated by the following example: manual application of high-density microneedles lead to a low penetration efficiency and a high variation on the penetration efficiency, whereas the same type of microneedles applied by using an impact (momentum) applicator lead to a high piercing efficiency with a high reproducibility (figure 2).

Figure 2 Application of 200-um long high-density microneedle arrays (2304 cm-2) onto ex vivo human skin by fifteen non-experienced microneedle users. Participants pierced the skin either by a manual insertion device (open circles) or by using an impact-insertion applicator (closed circles). Each point represents the average penetration efficiency of three individual microneedle applications by one individual (a) and the relative standard deviation (RSD) of the penetration efficiency for each participant (b) (adapted from: K. van der Maaden et al., The AAPS Journal (2014)).

Optimizing microneedle insertion parameters

In conclusion, because each type of microneedle device is different it will have different optimal application parameters to reproducibly insert microneedles into the skin, which is required for reproducible drug delivery. Furthermore, when a microneedle geometry is altered, microneedles are coated with a drug, or the microneedle composition is changed, the optimal insertion parameters will change. Therefore, we are developing digitally-controllable microneedle insertion devices based on impact (momentum) and pressure to enable a systematic investigation of the optimal microneedle insertion parameters.

Further Reading

 

PRODUCTS

Currently, our main technology (UAFM V1) comprises of an applicator and an applicator controller unit that can be used to investigate the optimal skin insertion parameters of microneedles. The device is primarily intended for universities, (research) institutes, and companies that work with, evaluate, and/or develop microneedle technologies. This device could be useful to anyone who is working on microneedle technologies to apply microneedles reproducibly and on the most efficiently manner, study the effect of microneedle geometry/material on skin penetration (whilst keeping the application conditions constant or as a function of the insertion conditions), and may be used to develop a simple, cheap, and patient friendly applicator for single-use (after the optimal insertion conditions are determined) to efficiently and reproducibly insert a specific microneedle product with a fixed force or impact into the skin.

The UAFM V1

The UAFM V1.0 is our first commercial universal microneedle application device. This research device was developed to investigate the optimal insertion parameters of different types of microneedles into skin. The microneedle application device consists of an applicator and an applicator controller unit. The applicator is used to insert microneedles/microneedle arrays into the skin, and is controlled by the applicator controller unit. Our device can be used to pierce microneedles into skin by three different manners:

  1. Application by pressure:
    • The applicator controller unit is set to apply microneedles via a predetermined pressure (Pressure Insertion Mode). Prior to application, the pressure (1 - 25 Newton), the application time (in seconds) and the time before application (in seconds) is installed on the applicator controller unit. When the button is pressed once, the supporting plateau of the applicator is in the protruding position. When the button is pressed an additional time, the applicator controller unit is counting down to zero. When the timer is finished microneedles are applied on the skin via the applicator that delivers the predetermined force during the application time (see video).
  2. Application by momentum:
    • The software on the applicator controller unit is set to apply microneedles via a predetermined momentum in two different modes:
      • Short Single Insertion:
        In this mode prior to application, the average velocity (25 - 85 cm/sec) and the application time (from 1 msec to 2 min) is installed on the applicator controller unit. When the applicator is placed onto the skin and the button is pressed on the applicator controller unit, the microneedles are inserted into the skin with the predetermined velocity. When the microneedles have been applied for the predetermined application time, the supporting plateau is automatically retracted into the applicator.
      • Continuous Insertion:
        In this mode only the average application velocity (25 - 85 cm/sec) is installable on the applicator controller unit. When the applicator is placed onto the skin and the button on the applicator controller unit is pressed, the microneedles are inserted into the skin with the predetermined velocity. During application the applicator controller unit shows the elapsed application time (in seconds). When the button is pressed a second time, the supporting plateau is retracted in the applicator.
  3. Repeated momentum application:
    • In this mode the applicator controller unit is set to apply microneedles via a repeated momentum (Mosquito Mode) onto the skin. This mode offers several different parameters to vary in order to optimize microneedle insertion and or drug delivery from microneedles into the skin. These parameters include:
      • The average application velocity (25 - 85 cm/sec)
      • The number (N) of insertions (2-100)
      • The application frequency (10 mHz - 10 Hz)
      • The onRate: the percentage of time of one insertion cycle that the applicator is pressing the microneedles onto skin (1 -99%)

Calibration

To deliver a precise predetermined amount of pressure (force in Newton) and average velocity (in cm/sec), each device (applicator-applicator controller unit combination) is externally calibrated (power to force/velocity). The calibration curves are integrated in the software to set the application pressure or application velocity during microneedle application.

Customization of the applicator

The supporting plateau - skin support combination of the applicator is exchangeable. The UAFM V1.0 applicator is standardly produced with a supporting plateau of 15 mm in combination with a skin support that has an opening of 17 mm. However, we can customize the dimensions of the supporting plateau - skin support combination of the applicator to apply differently-sized microneedle arrays onto skin. For customization possibilities please contact us at info@uprax.nl.

Alternative applicators

We are currently developing additional applicators that can be connected to the UAFM V1.0 applicator controller unit to offer additional experimental setups.

Figure 3 Schematic representation of the software functions.



PUBLICATIONS

K. van der Maaden, B. H. van Oorschot, J. Bouwstra, Electrically-controlled universal applicator for microneedle insertion (poster), MICRONEEDLES 2016, 4th international conference on microneedles, GSK house, London, 23-25 May 2016.

CONTACT US

For (pre)orders or more information please contact us at:
e-mail: info@uPRAX.nl
Deimanstraat 352
2522 BV Den Haag
The Netherlands