A facile system to evaluate in vitro drug release from dissolving microneedle arrays

AbstractThe use of biological tissues in the in vitro assessments of dissolving (?) microneedle (MN) array mechanical strength and subsequent drug release profiles presents some fundamental difficulties, in part due to inherent variability of the biological tissues employed. As a result, these biological materials are not appropriate for routine used in industrial formulation development or quality control (QC) tests. In the present work a facile system using Parafilm M® (PF) to test drug permeation performance using dissolving MN arrays is proposed. Dissolving MN arrays containing 196 needles (600μm needle height) were inserted into a single layer of PF and a hermetic “pouch” was created including the array inside. The resulting system was placed in a dissolution bath and the release of model molecules was evaluated. Different MN formulations were tested using this novel setup, releasing between 40 and 180μg of their cargos after 6h. The proposed system is a more realistic approach for MN testing than the typical performance test described in the literature for conventional transdermal patches. Additionally, the use of PF membrane was tested either in the hermetic “pouch” and using Franz Cell methodology yielding comparable release curves. Microscopy was used in order to ascertain the insertion of the different MN arrays in the PF layer. The proposed system appears to be a good alternative to the use of Franz cells in order to compare different MN formulations. Given the increasing industrial interest in MN technology, the proposed system has potential as a standardised drug/active agent release test for quality control purposes

Simple Variational-methods for Unbounded Potentials

We describe, for the first time, hydrogel-forming microneedle arrays prepared from "super swelling" polymeric compositions. We produced a microneedle formulation with enhanced swelling capabilities from aqueous blends containing 20% w/w Gantrez S-97, 7.5% w/w PEG 10,000 and 3% w/w Na2CO3 and utilised a drug reservoir of a lyophilised wafer-like design. These microneedle-lyophilised wafer compositions were robust and effectively penetrated skin, swelling extensively, but being removed intact. In in vitro delivery experiments across excised neonatal porcine skin, approximately 44 mg of the model high dose small molecule drug ibuprofen sodium was delivered in 24 h, equating to 37% of the loading in the lyophilised reservoir. The super swelling microneedles delivered approximately 1.24 mg of the model protein ovalbumin over 24 h, equivalent to a delivery efficiency of approximately 49%. The integrated microneedle-lyophilised wafer delivery system produced a progressive increase in plasma concentrations of ibuprofen sodium in rats over 6 h, with a maximal concentration of approximately 179 µg/ml achieved in this time. The plasma concentration had fallen to 71±6.7 µg/ml by 24 h. Ovalbumin levels peaked in rat plasma after only 1 hour at 42.36±17.01 ng/ml. Ovalbumin plasma levels then remained almost constant up to 6 h, dropping somewhat at 24 h, when 23.61±4.84 ng/ml was detected. This work represents a significant advancement on conventional microneedle systems, which are presently only suitable for bolus delivery of very potent drugs and vaccines. Once fully developed, such technology may greatly expand the range of drugs that can be delivered transdermally, to the benefit of patients and industry. Accordingly, we are currently progressing towards clinical evaluations with a range of candidate molecules