Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum

The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

AbstractWe describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml−1 at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm2 could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs

Hydrogel-forming and dissolving microneedles for enhanced delivery of photosensitizers and precursors

We present novel dissolving and hydrogel-forming microneedle arrays that can be applied in a one-step fashion and are intended to enhance delivery of photosensitisers and photosensitiser precursors. Microneedles (280 μm in length) were prepared from aqueous blends of 20% w/w poly(methylvinylether/maelic acid) and either crosslinked with glycerol by esterification to form hydrogels upon skin insertion or allowed to dissolve rapidly when inserted into skin. Drug-loaded patches containing either 19 mg cm(−2) of 5-aminolevulinic acid (ALA) or mesotetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) were attached to the MN during drug delivery experiments. Both MN types were mechanically robust, with even compression forces of 20.0 N only causing height reductions of around 14%. Application forces as low as 8.0 N per array allowed over 95% of the MN in each type of array to penetrate excised neonatal porcine skin and the MN penetrated to depths of approximately 280 μm, well beyond the stratum corneum barrier. MN significantly enhanced delivery of both ALA and TMP across dermatomed neonatal porcine skin in vitro, with the hydrogel-forming system comparable to the dissolving system for ALA delivery (approximately 3000 nmol cm(−2) over 6 hours), but superior for delivery of the much larger TMP molecule (approximately 14 nmol cm(−2) over 24 hours, compared to 0.15 nmol cm(−2)). This technology has the potential to improve convenience and efficacy of photodynamic therapy of neoplastic skin lesions. Consequently, we are currently planning animal studies, to be followed by preliminary human evaluations. Manufacturing scale-up is currently ongoing, with a view to patient benefit within 3-5 years