Formulation and Pharmacokinetic Evaluation of a Drug-in-Adhesive Patch for Transdermal Delivery of Koumine
- PDF / 1,195,678 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 95 Downloads / 228 Views
Research Article Formulation and Pharmacokinetic Evaluation of a Drug-in-Adhesive Patch for Transdermal Delivery of Koumine Yanping Su,1 Wenxiang Lu,1 Xiaoling Fu,2 Ying Xu,2 Lixiang Ye,3 Jian Yang,2 Huihui Huang,2 and Changxi Yu2,4,5
Received 10 May 2020; accepted 18 August 2020 ; published online 25 October 2020 Abstract. The aim of this study was to develop a suitable drug-in-adhesive patch for transdermal delivery of koumine. Acrylic polymer Duro-Tak® 87-4287, which contains hydroxyl groups, may significantly enhance the skin permeation of koumine from transdermal patches containing 0.93–3.72% koumine. Among permeation enhancers, 10% azone showed the greatest potential and increased the flux of koumine to 1.48-fold that of the control. Therefore, an optimized patch formulation containing 3.72% koumine and 10% azone in Duro-Tak® 87-4287 that offers good physical properties was selected for an in vivo pharmacokinetic study using rats. The maximal plasma drug concentration (Cmax) of koumine after transdermal administration (4 mg/patch) was 25.80 ± 1.51 ng/mL, which was in the range of those after oral administration (3 mg/kg and 15 mg/kg). The time to the maximal concentration (Tmax) and the half-life (t1/2) of the drug with transdermal administration were 3.96 ± 0.46 h and 21.10 ± 1.36 h, respectively, which were longer than those with oral administration. Furthermore, the area under the concentration-time curve (AUC0–72 h) of 898.20 ± 45.57 ng·h/mL for the transdermal patch was much higher than that for oral administration (15 mg/kg). In conclusion, the drug-in-adhesive patch containing koumine provides a steady plasma koumine level and sustained release in vivo and can be an effective means of transdermal delivery for koumine. KEY WORDS: koumine; drug-in-adhesive; transdermal delivery; skin permeation; pharmacokinetic study.
INTRODUCTION Gelsemium elegans Benth. (G. elegans) is a well-known toxic plant in China and Southeast Asia and has been widely used as a remedy for inflammatory diseases and pain (1,2). Studies have revealed that indole alkaloids such as gelsemine, koumine, gelsenicine, gelsevirine, and their analogues are the major active components in G. elegans (3,4). Koumine, the most abundant alkaloid of G. elegans, has been increasingly researched in recent years. The reported pharmacological
1
Department of Pharmacochemistry, College of Pharmacy, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China. 2 Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China. 3 Fujian Center for Safety Evaluation of New Drug, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China. 4 Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fuzhou, 350122, Fujian, People’s Republic of China. 5 To whom correspondence should be addressed. (e–mail: [email protected])
effects include antitumor, anti-psoriasis, analgesia, anxiolysis, and anti- rheumatoid arthritis (RA)
Data Loading...
