Texture Analysis in Research: Microneedles

Microneedle (MN) arrays are minimally-invasive devices used to penetrate the skin’s outermost layer, the stratum corneum, the principal barrier to topically-applied drugs. They are widely used in a range of applications including cosmetics and pharmaceuticals. Their use involves a simple, cheap, safe, and effective technique requiring minimal training. Microneedles were originally used as a collagen induction therapy for facial scars and skin rejuvenation, and still are, but are also now widely used in the form of patches as a transdermal delivery system for therapeutic drugs and vaccines. 

There have been countless publications of research into the properties and use of microneedle arrays for drug delivery using Texture Analysers, in both academic and industrial settings. These are the main areas of research:

• The compression of arrays into a known soft substrate such as animal skin or synthetic analogues, assessing the penetration force required for each array
• The measurement of the force applied by a human subject to an array on a soft substrate, generally performed on the calibration platform of the Texture Analyser
• The properties of the array backing material, measured using a tensile test
• The compression of arrays into a hard substrate to a known force. Needle strength is an important characteristic of arrays. Needles should be strong enough to be inserted into the skin without failure. The needle stiffness may be measured from the force-displacement graph and in some cases an ultimate strength may be measured as a breaking point on the graph. Most commonly, the percentage change in microneedle height due to buckling or blunting is assessed by measurement in a calibrated optical or electron microscope. The compression of needles into a metal base is a very different method from their insertion into skin. This test is simply used to compare different batches of arrays and confirm consistency of manufacture, or to assess the effect of different manufacturing processes on needle strength.

Some examples of the most recent research are outlined below.

Researchers from the University of Navarra have been investigating the dissolution of microneedles for intradermal vaccinations against Shigellosis. Vaccination is one of the main strategies to prevent and control infectious diseases. However, during recent decades, many efforts have been being made to obtain alternatives to conventional intramuscular or subcutaneous vaccine administration routes, which are mainly administered via hypodermic needles and need trained healthcare personnel. This study looked into the mechanical and dissolving properties of microneedle arrays as well as their immunogenic and protective capacity in mice. They used their TA.XTplus Texture Analyser to perform compression tests to assess percentage change of needle height as well as insertion force into a substrate. Since there is not a current licensed vaccine against shigellosis, this formulation is a promising candidate as a vaccine delivery system which could allow an easy and widespread immunisation in developing countries. Download article

Scientists from the University of Greenwich have been researching 3D printed microneedles for anticancer therapy of skin tumours. Over the last 20 years, microneedle devices have been used extensively for transdermal administration of various medicines in a non-invasive manner. Recent advances in the application of MN arrays to the skin involve the delivery of anticancer agents for the treatment of skin tumours. In this study, novel 3D printed polymeric microneedle arrays were fabricated for enhanced cisplatin delivery to A-431 epidermoid skin tumours for cancer treatment. They used their TA.HDplus Texture Analyser to measure the ability of MN arrays to penetrate skin. This study demonstrated the suitability of 3D printed microneedles in providing in-vivo transdermal delivery of anticancer drugs. Read more

Researchers from the University of Kent have been investigating a novel 3D printed hollow microneedle microelectromechanical system for controlled, personalised transdermal drug delivery. The advancement of drug delivery devices is critical for the individualisation of patient treatment and the improvement of healthcare. This paper introduces the 3DMNMEMS, a novel device that combines 3D printing, microneedles (MNs) and Microelectromechanical Systems (MEMS), allowing versatile and controllable by the user transdermal drug delivery. Hollow MNs were designed and 3D printed using Stereolithography, followed by integrating into a MEMS. By employing advanced imaging techniques, they monitored the distribution of liquid delivered by the device within skin tissue in real time. They used their TA.HDplus Texture Analyser to measure the ability of the MNs to pierce porcine skin and determine the penetration force. In vivo testing revealed that the delivery of insulin using the 3DMNMEMS achieved improved glycemic control to diabetic animals compared to subcutaneous injections. These results demonstrated the potential of the 3DMNMEMS as a universal transdermal drug delivery system for personalised care. Read more

Scientists from the University of Kent have been researching the optimisation of design and manufacturing parameters of 3D printed solid microneedles for improved strength, sharpness and drug delivery. 3D printing has emerged as a powerful manufacturing technology and has attracted significant attention for the fabrication of microneedle (MN)-mediated transdermal systems. This paper describes an optimisation strategy for 3D-printed MNs, ranging from the design to the drug delivery stage. The key relationships between design and manufacturing parameters and quality and performance were systematically explored. The 3D printed MNs were subjected to piecing tests in porcine skin using their TA.HDplus Texture Analyser. The printing and post-printing set parameters were found to influence quality and material mechanical properties, respectively. It was demonstrated that the MN geometry affected piercing behaviour, fracture, and coating morphology. The delivery of insulin in porcine skin by inkjet-coated MNs was shown to be influenced by MN design. Read more

Scientists at Queen’s University Belfast have been researching the efficiency of large microneedle patches for transdermal drug delivery, with the intention of using the technology in clinical drug delivery. They recently released a paper entitled “Successful application of large microneedle patches by human volunteers”. Microneedle arrays were self-applied to the skin by volunteers, with transepidermal water loss measured to confirm successful application. The needle strength of these patches was measured using an axial compression test to a set force on a Stable Micro Systems TA.XTplus Texture Analyser, with the array attached to the moving test probe of the Texture Analyser using double-sided adhesive tape. The change in needle height was monitored using a digital microscope. The texture analyser was also used for the controlled application of microneedle arrays to folded thin film artificial skin, for the purpose of inspecting the number of holes per depth once the sheet was unfolded. Read more

Scientists from the University of Aveiro have been researching pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment. This study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (Tdmax = 294 °C) and mechanical properties, penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. They used their TA.XT2 Texture Analyser to perform compression tests for needle strength as well as penetration tests into a substrate. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration. Read more

The assessment of the mechanical properties of microneedle arrays is a mandatory stage in their Research and Development. These properties may be altered by changes to raw materials, the drug being delivered, and the manufacturing process used. They must be measured after each iteration of ingredient or process modification.

To find out more about Texture Analysis of pharmaceutical products, contact Stable Micro Systems today.

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