Abstract
Faz Chowdhury is the Chief Executive Officer of Nemaura Pharma (Loughborough, UK), a pharmaceutical drug-delivery company developing patented formulation technologies alongside transdermal systems. Having originally trained as a pharmaceutical scientist, Dr Chowdhury received his PhD in Nanomedicine from the University of Oxford (Oxford, UK). With recognized expertise in the pharmaceutical industry and the holder of more than 15 patents on drug-delivery systems, Dr Chowdhury discussed the challenges faced in microneedle-based drug delivery, an area widely expected to revolutionize the transdermal field over the coming years.
Interview conducted by James Potticary, Commissioning Editor.
Q How did you become involved in the drug-delivery field, and specifically transdermal drug delivery?
I originally trained at Pharmacy School, which is where my interest in drug-delivery systems developed. I undertook further studies in Nanotechnology and Microsystems (MSc) and Nanomedicine (PhD) to advance my knowledge in the field. During the course of these studies, my research indicated that transdermal delivery provided a means of addressing some fundamental issues relating to medicine, in particular compliance and reduction in side effects through a combination of dosage reduction and avoidance of first-pass metabolism. However, it was clear that existing technologies were inadequate to deliver the large range of drugs that exist, and hence my decision to specialize in this particular field of drug delivery.
Q As CEO, would it be possible to update us on the current research projects Nemaura is involved in?
Nemaura have developed several platform technologies, and collectively these allow us to deliver almost any drug of any MW and physicochemical characteristics through the skin. Examples include reformulation of transdermal patches for Alzheimer's and Parkinson's disease in drug-in-adhesive matrix formats. At the other extreme we are undertaking a government-funded project to convert the Boostrix® vaccine from a liquid form to a micro-solid dose that can be instantly delivered through the skin using our economically produced, disposable proprietary solid dose delivery system, with strong potential for self-administration. This vaccine is inherently unstable if the cold chain is not maintained, and therefore in addition to potential self-administration we are examining the potential for dose sparing and enhanced stability that may eliminate the cold-storage requirements, thus setting a precedence to explore the delivery of other biologics and vaccines using this system.
Q Nemaura has strong links to academia and has previously licensed technology developed by researchers at the University of Bath (Bath, UK). How important are strong links with academia in today's competitive market?
Strong links with academia are fundamental to the growth and development of all industrial organizations that have a product development arm. There is often a fine line at the interface between the research phase and the development phase, and very often one is faced with scenarios where it is crucial to revisit fundamental scientific basis and principles during the development phase. This is where well-established links and ease of access to academic researchers is crucial. Additionally our universities are a rich source of intellectual property, and developing early links to help guide the development of such intellectual property is prudent in today's competitive environment.
Q The advantages of the transdermal route have been well-documented; however, as with any delivery method there are still challenges. What are the most significant hurdles you envisage over the next 5 years for the field as a whole?
With the advent of new technologies to enhance drug delivery through the skin the hurdles can be placed in three categories: formulation, device and end user. There will always be issues with respect to the formulation, in particular where there are stability- and potency-related considerations. For example, drugs with very low potency will not be suited to transdermal delivery, even when the barrier to delivery can be compromised temporarily; hence the ability to create active pharmaceutical ingredients of adequate potency is key to ensuring more drugs can be delivered via this route. The physicochemical properties are less of a consideration in light of technologies that exist today to enhance skin permeation of drugs.
Device considerations will focus around cost and ease of use. Many devices such as those utilizing laser energy sources, or sonic wave generators, are cumbersome and expensive and are not always intuitive to the end user; considering the issues of poor compliance that exist with something as simple as swallowing a tablet, processes that involve multiple steps or indeed the use of devices are likely to lead to compliance issues. Furthermore, the latter issue will also lead to serious regulatory concerns, in particular where the rapidly evolving development of devices for transdermal delivery are operator dependent, which will inherently lead to large variations in dosing. Transdermal systems therefore need to be compact, cheap and easy to administer in a robust and reproducible format.
Q Microneedles are widely expected to revolutionize transdermal delivery. Would you agree with this sentiment, or do you feel that other transdermal technologies could be equally or more revolutionary?
I would agree and disagree. Microneedles will revolutionize the delivery of vaccines in particular, predominantly due to the dose-sparing effect as a result of the enhanced immunogenic response achieved from delivering the drug in proximity to the immune-stimulating cells in the skin. Conversely, this poses issues with the delivery of biologics, for example, where unwanted immunogenic responses may be achieved. Second, vaccines do not require chronic administration and therefore puncturing the skin temporarily on an infrequent basis is unlikely to cause any serious concerns for potential skin infection. However, drugs requiring chronic administration require a number of considerations:
Microneedles breach the skin barrier by creating temporary micro-conduits across the skin, allowing the delivery of drugs either by passive diffusion, or actively by inserting the drug into the skin coated on the needles or by forcing the drug into the skin through hollow bores of microneedles. While early research indicates that micro-organisms generally do not enter the skin when pretreated with micro-needles, this will no doubt be a function of skin thickness, the way in which the device is applied to the skin by the patient, and general hygiene of the user, and has important safety ramifications that need to be addressed and overcome before microneedles can be adopted more widely.
Microneedle patches can vary from several dozen to several hundred needles on a patch. Reproducibility of dosing is a fundamental challenge that must be adequately validated. In order to achieve this one must address the following: that each needle is inserted to the same depth in the skin, every time, in every patient, and remain in the skin for the duration required without the needles popping out of the skin, and all of this must be independent of the user. It is logical to assume, and indeed demonstrated in literature that the extent of insertion of the needles is dictated by where the force is applied and the duration for which the force is applied, and in the event the path surface area is beyond a threshold the forces will not be evenly distributed, more so as there are few regions on the body where the skin surface is completely flat. While encouraging data is emerging from controlled clinical evaluation, the full scale of the issues will only be evident when the mass population come to use these systems, and it is incumbent upon the industry to address these very challenging issues to promote the widespread use of microneedle technologies.
What would be revolutionary is a technology where it is possible to deliver a defined dose into the skin almost instantaneously, in an operator-independent manner that does not require either any skin preparation, other than perhaps an alcohol swab, and does not require one to retain the device/patch on the skin. This can be achieved with some solid dose injectors.
Q What key advantages do microneedles hold over other technologies designed to deliver therapeutics past the skins barrier?
The main advantage is that the restrictions posed by the primary barrier to the passage of drugs through the skin, the Stratum Corneum, and the relative solubility of the drug in the uppermost layers of the skin are bypassed, hence opening up the possibility of delivering a large range of drugs of varying MWs and physicochemical properties.
Q Challenges associated with microneedles include reproducibility of dosing and skin irritation. Do you believe these can be easily overcome, and if so, how?
Reproducibility of dosing can be overcome by applying the needles over the skin a single row at a time, which ensures that each and every needle penetrates the skin (e.g., by applying the microneedles to a flexible patch on a roller). Pressurized delivery mechanisms that use high forces require the force to be distributed over a large surface area, and this is quite challenging since the thickness of the skin and variations in skin contour can affect the number of needles that penetrate the skin.
With respect to skin irritation, breaching the skins barrier will inevitably cause some degree of skin irritation. However, there are ways to minimize the extent and duration of skin irritation through careful selection of materials, and methods to minimize the trauma to the skin on needle insertion.
Q Microneedles are produced as either solid or hollow structures and can be manufactured from a range of materials. What do researchers generally take into account when considering a microneedle design?
Key parameters that are considered depend on whether the needle is solid or hollow, and whether the needle is produced from or coated with the drug of interest, or simply intended to be used as a skin-prep device without any drug directly applied. However, two important parameters that apply to all systems are aspect ratio/geometry and tip sharpness, which dictates the ease of skin insertion, and secondly material of fabrication, which dictates the manufacturing process.
Q With only one microneedle-based device currently on the market, what are the main problems associated with gaining regulatory approval of these products?
Key regulatory issues surround accuracy and reproducibility of dosing, and safety.
Q What advice would you give to a young, aspiring scientist considering a move from academia to industry?
Develop an area of interest that you are passionate about and become a specialist in that area, while always keeping abreast of the broader developments in the field and how they impact on your particular area of specialism.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Future Science Ltd.
Financial & competing interests disclosure
Nemaura are involved in drug delivery through the skin. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.