Pharmaceutical development and characteristics of a new glyceryl trinitrate transdermal patch

The pharmaceutical development and characteristics of the new glyceryl trin itrate (GTN, CAS 55-63-0) transdermal patch Epinitril(R), hereinafter calle d EPI, are described. EPI is a thin (0.096 mm), transparent patch, with GTN uniformly dissolved in a monolayer pressure-sensitive acrylates vinyl acet ate copolymer adhesive matrix. The patch provides an intense flux rate of G TN through the skin (33 mug/cm(2)/h). This is the result of the high concen tration of GTN in the matrix (39.3 % w/w) and of its thinness (0.033 mm), w hich elicit a high thermodynamic activity of GTN on the surface of the skin , promoting its absorption. EPI was developed in three strengths with relea se rates of 5, 10 and 15 mg GTN in 24 h, to allow the adaptation of the dos e to the needs of the individual patient. During development, different tes ts were used to evaluate in vitro the release of GTN, i.e. a) the disk asse mbly dissolution test, b) the artificial membrane-controlled dissolution te st and c) the diffusion test through the stratum corneum and epidermis of h uman skin. None was able to provide a reliable in vitro-in vivo correlation of the performance of the investigated patches. The tests, however, are us eful to evaluate the effects of formulation changes during pharmaceutical d evelopment. For its small size, thinness, flexibility, transparency, easiness of applic ation and of removal and for its good tolerability, EPI is very patient fri endly, a quality that improves the compliance with the long-term therapeuti c courses needed in angina pectoris.