Study On Transdermal Delivery System Of Tulobuterol

As the3rd generation of β2receptor agonist, tulobuterol plays an important role in the treatment of bronchial asthma, asthmatoid bronchitis and chronic bronchitis in clinical practice, not only due to its effect of antianaphylactic, antitussive, but also due to its effect of enlarging the bronchia smooth muscle and promoting airway ciliary beating[1-6].Patients with bronchial asthma often suffer the disease during the period from midnight to tomorrow morning because of the decreasing respiratory functions. Their blood concentration decreases after taking conventional oral medication8to10hours before bedtime and simultaneously the hearts are excited because of higher Cmax value. Thus, there are some drawbacks of the conventional oral medication in the treatment of asthma. In this project, tulobuterol was prepared into patch with double-layer structure of pressure-sensitive adhesive of which can attain the purpose of sustained-release curing and in the prevention and treatment of asthma disease effectively.Four chapters about the topic are included as following.Chapter1Study on the Physicochemical Properties of Tulobuterol Bulk PharmaceuticalsThe physicochemical properties of tulobuterol bulk pharmaceuticals were manily focused on the aspects of the solubilitis in fat-soluble solution and water-soluble solution respectively, oil/water partition coefficient while phosphate(pH=7.4) was employed as the acceptor solution of the transdermal experiments. The results from the oil/water partition coefficient show that the logP value ranged-1to0.4and increase as increasing pH value of the phosphate solution.Chapter2Study on Optimization of Formulation and Preparation Technology of Tulobuterol PatchThe effect of polyisobutylene B50, PB1300and cycloparaffin NAPHSOL200on the permeation rate of the tulobuterol, the ball tack and hold tack of the patch were studied by designing the orthogonal test. The effect of different forms of spreading on permeation rate of the drug was investigated, respectively. According to the optimum formula with the proportion of B50:PB1300:NAPHSOL200≈1.5:1:1, the double-spreading method with the dose of2to1was accomplished as the optimum preparation technology. The results show that the optimized transdermal patch prepared with suitable viscosity permeats stably and matches the controlled releases tandard.Chapter3Study on the Quality Evaluation of Tulobuterol PatchAn accurate, reliable and specific HPLC analytic method was established to the quality research of transdermal patch. The quality evaluation of tulobuterol patch prepared using the optimized formulation was carried out by evaluating the drug concentration, the viscosity, the ding release degree, the transdermal permeability, the stabilization, the skin irritation and the drug concentration. The results show that both the concentration of the patch and the concentration uniformity match the corresponding requirements of pharmaceutics. Both the ding release degree and the transdermal ratio are good. The viscosity is suitable and no skin irritation is investigated to New Zealand rabbit indicating tulobuterol patch is superior in stability.Chapter4Study on the Pharmacokinetic of Tulobuterol PatchThe pharmacokinetic of tulobuterol patch was studied in rats. An analytic method of LC/MS/MS was developed firstly. With reference to tulobuterol patch of a specimen corporation, the sorption curves characteristicsof the optimized patch was investigated in rats. The results suggest there is little statistical difference in main pharmacokinetic parameters between the optimized patch and the patch of the specimen corporation, and the relative bioavailability of the former is104.9%, better than the latter.In this present work, a kind of tulobuterol patch with double-layer structure of pressure-sensitive adhesive was developed successfully. The patch matches every quality investigation indexr and achieves the purpose of drug treatment of asthma disease. The transdermal experiments in rats show that each index basically meets the level of the patch of the specimen corporation. This principle of controlled-release double structure applied innovate supplies a new technology for the research and the development of controlled release patches.