Studies On Formulation Of Matrix Type Tetramethylpyrazine Patch

2,3,5,6-tetramethylpyrazine (TMP) is a biologically active ingredient originally isolated from Ligusticum wallichii Franch and currently used in China for the treatment of cardiovascular disease. Oral administration of TMP is known to exhibit extensive first-pass metabolism, low oral bioavailability;intravenous infusion TMP administration cause pain, irritation and the potential risk of infections, which decreases the compliance. Transdermal patch could offer a variety of significant clinical benefits over other dosage forms. Because transdermal drug delivery offers controlled release of the drug into the patient, it enables a steady blood-level profile, resulting in reduced systemic side effects and, sometimes, improved efficacy over other dosage forms. In addition, because transdermal patches are user-friendly, convenient, painless, and offer multi-day dosing, it is generally accepted that they offer improved patient compliance. In this study we develop a TMP transdermal delivery system (TDS) .During the preformulation study, the influence of pH on the percutaneous permeation of TMP was studied in vitro using hairless mouse skin. The result suggests TMP could easily penetrate through stratum corneum at pH-neutral level, don't have a reservoir effect within the stratum corneum. In vitro drug release of tetramethylpyrazine hydrochloric (TMPH) transdermal patch is studied. The result indicates the diffusion coefficient of TMP in the matrix is smaller than skin, the release of TMP from adhesive is very hard.Duro-Tak polyacrylate pressure sensitive adhesive are used as matrix for TMP transdermal patch. Permeation of TMP through SD rat dorsal skin, drug crystallization and the patch adhesiveness are studied and the influence of different factors (type of adhesive, presence of enhancers, polymer, solvent are investigated. Moreover, optimal formulation is achieved by single factor experiment. Optimal TMP patch is single layer matrices type, that values of tack adhesion, peel adhesion, shear, (dQ/dt)_ss, Q_24h M_t /M_∞ were 18 steel ball,0.03KN/m, 72min, 289.32±72.10 (ug · cm-2 · h-1 ) , 4409.97±631.67 (ug · cm-2) ,60%. In this paper, many problems such as small dose poor adhesiveness and low percutaneous permeation rate about insoluble drug like TMP adhesive patches have been solved. Prepared polyacrylate adhesive patch with 20%(w/w) TMP meet the requirement of patch standard, and the cumulative release amount of TMP at 30cm2 achieve the requirement of transdermal therapy. It can be a good substitute for reservoir TDS.