Pharmaceutical Development and Characteristics of a New Glyceryl Trinitrate Transdermal Patch

Abstract

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.

Smart Skin‐Adhesive Patches: From Design to Biomedical Applications

“…Thus, the chosen materials must be chemically inert, have limited permeation to the drug, and have a low affinity toward water. [ 74 ] However, cross‐linking is often formed between the adhesive and the release liner before usage and an unacceptably strong force may be required to remove the liner (e.g., Scotchpak 1022 and Scotchpak 9742, 3 M Drug Delivery Systems, St. Paul, MN, USA). [ 75 ]…”

Assessment of Skin Safety of a New Glyceryl Trinitrate Transdermal Patch

“…Circular, light yellow and transparent, monolayer matrix glyceryl trinitrate (GTN) transdermal patch originated, patented and produced by Rotta Research Group (Epinitril  , Dermatrans  ). EPI is formed by an outer covering 33 µm-thick polypropylene backing foil and by a drug-containing 63 µmthick adhesive matrix, in which GTN is dissolved [30]. The matrix is a pressure-sensitive adhesive, namely a copolymer of acrylates and vinyl acetate (Durotak 387-2516) with a crosslinker (polybutyltitanate) and a tacking resin (hydroabietyl phthalate) to correct the properties of the adhesive altered by the addition of GTN.…”

“…With the goal to further improve these characteristics, we have developed a GTN transdermal patch using a new technology that avoids absorption enhancers and increases the transdermal absorption [31]. The pharmacokinetic performance of the new GTN patch was previously described [28,29] as well as its pharmaceutical characteristics [30]. In this publication we report the in vitro and in vivo models and the studies in man employed to assess the skin and general safety of the newly developed GTN transdermal patch.…”