Development of Microneedles for Transdermal and Intradermal Drug Delivery

Abstract

Transdermal drug delivery has an enormous potential for painless therapeutics. Many drugs designed for systemic action are more efficient when delivered through the skin compared to oral administration as their degradation in the digestive tract is prevented. Vaccines delivered in the skin(Intradermal) also require much less dose volume compared to conventional intramuscular route for the same efficacy. Since transdermal delivery is painless, it can present a great advantage to people dependent on daily injection therapies like insulin. However, molecular weight of topically applied drugs that can penetrate through the skin is limited to 400 Da. The main challenge in achieving a successful drug delivery through the skin involves designing strategies to overcome permeation resistance offered by the top skin layer called stratum corneum (SC). Tiny, sharp projections designed to penetrate SC, called ”Microneedles” are very effective in enhancing this molecular weight limit.

Any new product development cycle involves a sequential process of design, identification of feasible manufacturing processes, development of a first successful prototype, pilot batch fabrication, testing and mass manufacturing after successful testing of the pilot batch. But for a specialized segment like microneedle manufacturing, several iterations may be required between design and testing phase. For the microneedle fabrication techniques reported in the literature, involving use of sophisticated technologies and equipment, the costs involved in iterating designs are extremely high. Major challenge in enhancing the utility of microneedles for widespread applications lies in cutting down the cost of fabrication methods and increasing the flexibility of tweaking geometric parameters. The present thesis discusses methods developed for fabrication of microneedles keeping design simplicity, flexibility and multiplicity in perspective. In first part of the thesis lithography methods were explored for the fabrication of solid SU8 microneedles and their limitations are discussed. In later parts, a syringe retrofit hollow microneedle device for generic drug delivery, made using stainless steel needles is discussed. The device has been extensively tested on animals and its utility has been verified. In the final part, a variable aspect ratio molding platform for fabrication of solid and dissolvable microneedles is discussed. This unique platform offers the capability of fabricating series of needle patches with heights ranging from as low as 200-300 μm to as high as1800-2000 μm with resolution of 50 μm. The platform’s capability of fabricating hollow microneedle patches using drop casting method and a metered dosing package for them is also discussed. Overall, the work presented in this thesis takes a step towards development of a low-cost product with a potential of productionization.