Studies On Transdermal Delivery System Of Tulobuterol And Its Characteristic Penetrated Through Rat Skin

Tulobuterol-HCl {α -[(tert-butylamino)methyl]-o-chlorobenzyl alcohol hydrochrode} is a β₂-adrenoceptor agonist having a potent and long-lasting effect.We developed a new tulobuterol transdermal therapeutic system. The patch offer many advantages over the conventional dosage forms, including constant blood levels, avoids first-pass metabolism, increased compliance.In this paper, the transdermal characteristic of tulobuterol and tulobuterol patch were studied.A high performance liquid chromatography(HPLC) method was developed to determine the concentration of tulobuterol.The conditions was as follows, Diamonsil^TM diamond C₁₈ column(4.6mm×250mm,5um);UV detective wavelength 211nm;flow rate 1. 0ml/min;sensitivity 0. 01AUFS;mobile phase is composed of methanol :0. 01mol/ml potassium dihydrogen phosphate aqueous solution (40:60) for in vitro samples and blood samples. By which the interference of impurity may be avoided and there is a good linear relationship between concentration and peak area.Molular formula of tulobuterol was C₁₂H₁₈CLNO, Molecular weight was 227. 73, Melting point was 89-91℃。LogP was determinted, the results indicated determination of partition coeffocient is 5. 66[PH7. 4, 1-octanol/buffer]. The steady state flux(J) and permeability coefficient(P)of tulobuterol was investigated with different receptor solution and different drug contents in vitro percutaneous penetration experiments, the results indicated high concentration may enhance the steady state flux(J) of tulobuterol and PBS7. 4 was used as receptor solution.The components of matrix was optimized by uniform design, While adhesion strength and cohesive strength were used as indexes. Tulobuterol in hydrophilic patch was permeated at zero rate and the cumulative penetrating...