Optimizing Characterization for Microneedle Drug Delivery Technology

By:

Andrew Riso, Vice President, Dermal Delivery and Licensing, Kindeva Drug Delivery

Ben Newton, R&D Engineering Manager, Kindeva Drug Delivery

Dr. Scott Burton, R&D Principal Scientist, Kindeva Drug Delivery

Vinh Hua, Lab Manager, Kindeva Drug Delivery

Dr. Mahmoud Ameri, President, Americeutics Consulting

First-generation transdermal patches were limited to hydrophobic molecules and small molecular sizes. Newer microneedle array patches (MAPs), however, can deliver a wider range of drugs directly into the dermis of the skin, including peptides, proteins, and vaccines.1 Microneedle drug delivery bypasses the gastrointestinal tract, avoiding first-pass metabolism and allowing for rapid and efficient therapeutic effects.2

While offering the potential for broad-reaching benefits, MAPs present pharmaceutical companies with challenges spanning from early development to commercial scale-up. By optimizing analytical and performance characterization approaches, developers and manufacturers can streamline processes to enable the effective creation of microneedle drug delivery systems.

Understanding microneedles

MAPs consist of solid drug-coated needles arranged in a small, adhesive-backed array. Upon application, the microneedles penetrate the outer layer of the skin and deliver the drug into the dermis. This mechanism allows the active pharmaceutical ingredient (API) to reach capillaries without stimulating pain receptors, making it a patient-friendly alternative to intramuscular injections.1

Applying MAPs with an applicator can help improve patient outcomes through more consistent dosing, enhanced bioavailability, and minimized discomfort.1 This technology also opens new possibilities for scaling complex formulations while simplifying storage and logistics by eliminating or reducing the need for cold-chain requirements.3

Taking advantage of these benefits requires rigorous validation. Analytical techniques play a critical role in ensuring that microneedle technology delivers consistent, reliable results across diverse patient populations and therapeutic needs.

Choosing the right methods for analytical characterization

The assessment of MAPs begins with analyzing API content and excipients to confirm that the finished product will deliver a consistent dose - an essential factor for clinical reliability. High-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC) are particularly valuable tools here, enabling developers to quantify drug concentration and uniformity across arrays.

To evaluate stability, samples are tested under varying temperature and humidity conditions following International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. This approach detects impurities and degradation products using techniques such as HPLC/UPLC and liquid chromatography–mass spectrometry (LC-MS).

Stability extends beyond the API to include the physical components of the patches. Adhesion properties, dissolution rates, and the integrity of packaging systems are all key factors. For example, dissolution studies simulate wear-time scenarios to confirm the rapid release of the coating.

Finding effective performance testing strategies

The efficiency of microneedle drug delivery depends on several interrelated variables. The design of the microneedle patch -? including the length, spacing, and shape of the needles - directly impacts the penetration depth and delivery rate.4,5 Arrays with varying configurations allow for tailoring to specific therapeutic applications.

Advanced imaging and real-time monitoring systems play a role in both development and production. For example, vision systems used during manufacturing can measure drug coating volume and distribution across needles. These systems enable real-time adjustments, improving the therapeutic performance of the finished patch product..

Performance testing highlights the interaction between each array’s physical properties and its delivery capabilities. For instance, increasing droplet size enhances delivery up to a point, after which efficiency plateaus or declines due to insufficient energy for complete penetration.1 These findings drive optimization in both formulation and device design, aligning product capabilities with therapeutic goals.

Carrying out non-clinical and clinical validation

Establishing the safety and efficacy of microneedle array patches (MAPs) can include both non-clinical testing in animal models and clinical trials. This validation process ensures that MAPs perform consistently and meet regulatory standards.

Non-clinical testing

Animal models are instrumental in understanding how MAPs interact with the skin and deliver therapeutic agents during non-clinical testing. Pigs are often the preferred model due to the similarities between porcine and human skin in terms of thickness, elasticity, and immunogenicity in the case of vaccine delivery.6 These characteristics make pigs an ideal surrogate for studying drug penetration, pharmacokinetics, and immune responses.

Using a kinetic applicator, MAPs are applied with uniform force to minimize variability. The efficiency of drug delivery is then quantified by measuring residual drug left on the patch and skin surface. This provides a precise estimate of the dose delivered intradermally.

Other animal models, such as rabbits and rats, are used for specific purposes, including the evaluation of local tolerability and immunogenicity.6 While rodents are cost-effective and easy to handle, their thinner skin layers require careful application to avoid subcutaneous delivery. Rabbits, with their thicker skin, provide a middle ground, particularly in studies of intradermal vaccine delivery.

Clinical validation

Building on non-clinical findings, clinical trials confirm the safety and efficacy of MAPs in humans. Early-phase trials focus on parameters such as immune response consistency and tolerability. For instance, a Phase I trial of flu vaccines delivered via MAPs demonstrated comparable immune responses to intramuscular injections.7 Antibody titers remained elevated six months post-vaccination, and patient preference leaned strongly toward the patch due to its non-invasive nature.

Further trials assess long-term outcomes and scalability. A Phase III study of a microneedle-delivered osteoporosis drug involved over 500 patients self-administering the patch daily for a year. With more than 120,000 applications recorded, no incidents of skin infection were reported, showcasing the patch’s safety profile.7 The pharmacokinetic profiles remained consistent across the study period, with no evidence of anti-drug antibody formation.

Addressing practical and environmental concerns

Once development considerations have been addressed, commercialization presents an additional hurdle. Scaling up MAP production involves addressing manufacturing efficiency, cost reduction, and environmental sustainability. Innovations in precision molding and coating technology enable high-volume production while maintaining quality, supporting pharmaceutical companies in harnessing the benefits of MAPs while optimizing manufacturing efficiency.

Unlocking the potential of microneedles

Microneedle array patches represent a step forward in drug delivery, with the potential to improve patient compliance through their ease of use and minimal discomfort. As the technology advances, the potential for self-administered therapies, integrated with telemedicine and wearable health devices, continues to grow.

In a recent webinar, we discussed microneedle patches in more detail, with insights into methods to improve characterization and ease the process of commercialization. For a deeper dive into the possibilities of microneedle drug delivery, download the webinar replay.

References:

1. Avcil, M., and ?elik, A. “Microneedles in Drug Delivery: Progress and Challenges.”?Micromachines (Basel). 2021;12(11):1321. doi:10.3390/mi12111321?

2. Jung, J.H., and Jin, S.G. “Microneedle for transdermal drug delivery: current trends and fabrication.” J Pharm Investig. 2021;51(5):503-517. doi:10.1007/s40005-021-00512-4?

3. Kim, Y.C., Park, J.H., and Prausnitz, M.R. “Microneedles for drug and vaccine delivery.”?Adv Drug Deliv Rev. 2012;64(14):1547-1568. doi:10.1016/j.addr.2012.04.005?

4. Waghule, T., Singhvi, G., Dubey, S.K., et al. “Microneedles: A smart approach and increasing potential for transdermal drug delivery system.”?Biomed Pharmacother. 2019;109:1249-1258. doi:10.1016/j.biopha.2018.10.078?

5. Loizidou, E.Z., Inoue, N.T., Ashton-Barnett, J., et al. “Evaluation of geometrical effects of microneedles on skin penetration by CT scan and finite element analysis.”?Eur J Pharm Biopharm. 2016;107:1-6. doi:10.1016/j.ejpb.2016.06.023?

6. Wei, J.C.J., Edwards, G.A., Martin, D.J., et al. “Allometric scaling of skin thickness, elasticity, viscoelasticity to mass for micro-medical device translation: From mice, rats, rabbits, pigs to humans.” Scientific Reports. 2017;7:15885. doi:10.1038/s41598-017-15830-7

7. Data from Kindeva Drug Delivery & partner research.

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