Transdermal Drug Delivery System. Stage 1. Volume 3

The US Army requested proposals for a four-stage program aimed at the development, optimization, and production of a transdermal drug delivery system TDDS for the drug, pyridostigmine bromide. Stage I of the work had the objective to explore alternative TDDS concepts and proposed the simultaneous exploration of three design approaches the drug incorporated into 3M proprietary hypoallergenic adhesives, the drug incorporated into a gel diffusion matrix, and the drug delivered from an iontophoretic system. During a five-month feasibility study, Medtronic, Inc. provided and tested an iontophoretic system. Preliminary in vitro and in vivo results indicated that pyridostigmine bromide could be delivered by this approach. A series of 3M hypoallergenic adhesives was formulated with pyridostigmine bromide. In vitro skin penetration of pyridostigmine bromide from nonpolar adhesive based systems was very low, and polar adhesive based systems did not have acceptable physical properties for a pressure sensitive adhesive. A wide range of components were incorporated into polyvinyl alcohol based gel diffusion matrices. The formulations were screened both in vitro and in vivo and they met initial delivery requirements.