Pharmaceutical development and characteristics of a new glyceryl trinitrate transdermal patch
The pharmaceutical development and characteristics of the new glyceryl trinitrate (GTN, CAS 55-63-0) transdermal patch Epinitril, hereinafter called EPI, are described. EPI is a thin (0.096 mm), transparent patch, with GTN uniformly dissolved in a monolayer pressure-sensitive acrylates vinyl acetate copolymer adhesive matrix. The patch provides an intense flux rate of GTN through the skin (33 micrograms/cm2/h). This is the result of the high concentration of GTN in the matrix (39.3% w/w) and of its thinness (0.033 mm), which elicit a high thermodynamic activity of GTN on the surface of the skin, promoting its absorption. EPI was developed in three strengths with release rates of 5, 10 and 15 mg GTN in 24 h, to allow the adaptation of the dose to the needs of the individual patient. During development, different tests were used to evaluate in vitro the release of GTN, i.e. a) the disk assembly dissolution test, b) the artificial membrane-controlled dissolution test and c) the diffusion test through the stratum corneum and epidermis of human skin. None was able to provide a reliable in vitro-in vivo correlation of the performance of the investigated patches. The tests, however, are useful to evaluate the effects of formulation changes during pharmaceutical development. For its small size, thinness, flexibility, transparency, easiness of application and of removal and for its good tolerability, EPI is very patient friendly, a quality that improves the compliance with the long-term therapeutic courses needed in angina pectoris.
Santoro
A
Department of Development and Regulatory Affairs, Rotta Research Laboratorium, Monza, Italy.
Rovati
LC
Lanzini
R
Setnikar
I