ABSTRACT
OBJECTIVE: To prepare of a torotrope transdermal patch for in vitro consistency evaluation and explor of the impact of quality standard characteristics on industrialization. METHODS: The tulobuterol transdermal patch was prepared with polyisobutylene B50, polybutene and petroleum resin as auxiliary excipients. The drug content in the sample was determined by high-performance liquid chromatography; in vitro consistency was evaluated by microscopy, differential thermal analysis, Fourier transform infrared spectroscopy, viscosity tester, dissolution Tester, and transdermal tester. The dissolution of the patch and its relationship with transdermal permeation, drug crystallization and in vitro release mechanism of the patch were studied in order to explore the influence of quality standard characteristics on industrialization. RESULTS: The self-made patch and the reference preparation have conformity in the drug content, drug crystallization, DSC, MATR, heat resistance, cold resistance, viscosity and shape. The dissolution tests were performed in medium of water and phosphate buffer (pH 7.4, 6.8, 4.0), and the corresponding f2 were 72.516, 94.840, 90.905, and 81.760. The average transdermal permeability ratio is 1.02 and the skin retention ratio is 0.88. The drug solubility is pH dependent while the in vitro dissolution is not sensitive to pH. The correlation between transdermal and dissolution in vitro is good. The in vitro release is affected by the composition of the excipients and the crystallization of the drug. CONCLUSION: The self-adhesive and the reference preparation have good consistency in vitro evaluation; the in vitro dissolution test can effectively reflect the transdermal permeation and absorption process of the drug in vitro. The drug crystallization evaluation index in the preparation is introduced to improve the quality control detection efficiency and quality assurance in the industrialization process. Research reference is provided for the consistency evaluation research, industrialization and quality standard improvement of this product.
ABSTRACT
OBJECTIVE: To prepare the tulobuterol crystal reservoir patch, and to evaluate morphology, stability and crystallization factors of the crystal in the patch, adhesive force, dissolution, transdermal properties in vitro and the pharmacokinetics in rabbits. METHODS: The transdermal patch was prepared on the basis of drug recrystallization and characterized by morphology, stability and crystallization factors using microscope and adhesive force using initial adhesion tester, adhesion tester and peel tester. The dissolution and transdermal properties were evaluated by using the dissolution tester and transdermal tester. In addition, pharmacokinetics was studied using New Zealand rabbits as experimental animals. RESULTS: The drug crystals were evenly distributed in the form of filaments, which had average width of (4.4±1.8)μm and kept stable at 2-40 ℃. The crystallization in patches is affected by tulobuterol supersaturation and temperature. The adhesive force of patch was suitable and its dissolution matched standard which can be fitted by the Higuchi equation. In the diffusion cell in vitro, the drug penetrated through the skin in a Zero-order kinetic equation, and the cumulative penetration percentage and skin retention concentration were 92.04% and 10.36 μg·cm-2 with in 24 h. The pharmaceutic parameters showed that the tulobuterol blood concentration can be maintained within 24 h, whose tmax and ρmax were (6.67±3.06)h and (3.08±1.32) ng·mL-1, respectively. CONCLUSION: The tulobuterol crystal reservoir patch can be established by control of recrystallization conditions. The patch has good adhesive properties and sustained release characteristics in vitro and in vivo, which has the practical significance for further study.