OBJECTIVE To prepare aminophylline patches and study the pharmacokinetic characteristics in rabbits after application on navel. METHODS Aminophylline patches were prepared by hot-envelop method. Modified Franz diffusion cells were employed to screen permeation enhancers with excised rat abdomen skins as diffusion barrier. The concentration of aminophylline in rabbit plasma was determined by HPLC after aminophylline solution was irrigated intragastrically and the aminophylline patches were applied on notum and navel， respectively.Pharmacokinetic parameters were calculated and the pharmacokinetic profiles were characterized by comparing the above three groups with statistical analysis. RESULTS Based on the excised rat skin permeation test， 3% menthol-propanediol (1∶1) mixture was the optimal permeation enhancer with a steady state permeation rate of （9.08 ± 0.21） μg·cm-2·h-1. The main pharmacokinetic parameters of， notum application group and navel application group were as follows： ρmax were (13.42±1.10)， (4.53±0.39) and (5.77±0.44) μg·mL-1and tmax (1.83±0.29) , (5.67±0.58) and (4.33±0.58) h， AUC0→t (47.65±3.46)， (31.65±4.11) and (39.97±3.14) μg·h·mL-1，t1/2 (1.90±0.30)、(2.45±0.07) and (1.90±0.06) h， Ka (2.01±0.55)， (0.33±0.02) and (0.55±0.04) h-1， tlag were (0.19±0.04)、(0.59±0.03) and (0.32±0.19) h，respectively.The relative bioavailabilities of aminophylline after notum and navel application were (67.41±19.11)% and (84.81±18.03)% respectively compared with intragastrical irrigation group. CONCLUSION The preparation process of aminophylline patches with desirable skin permeation property is practicable. Aminophylline patches are able to realize sustained-drug release and have higher bioavailability after navel application compared with notum application.
GAO Xiao-yu， WANG Cong-yao， WEI Ying-hui， XU Xiu-ling， ZHENG Hang-sheng， YE Jiao-yun， LI Fan-zhu.
Preparation of Aminophylline Patches and Their Pharmacokinetics in Rabbits After Navel Adminstration[J]. Chinese Pharmaceutical Journal, 2012, 47(23): 1925-1929
[1] LIU H Y， PI X T， ZHENG X L， et al. Studies on pharmacokinetics of aminophylline site-specific delivery capsules released in the proximal small intestine[J]. Chin Pharm J（中国药学杂志），2007，42(23)：1807-1809. [2] ANDERSON M. The properties of aminophylline[J]. Emerg Nurse，2007，15(7)：24-27. [3] XU J， LI Y， XU J， et al. Analysis of serum concentration of aminophylline for treating asthma in pediatrics[J]. J Pediatric Pharm（儿科药学杂志），2004，10(1)：31-32. [4] SHI W Q， NI W. Clinical research of effect of umbilical Chinese material paste on endotoxemia of cirrhosis patients[J]. Chin J Tradit Chin Med Pharm（中华中医药杂志），2010，25(3)：452-455. [5] YIEW W C. Navel absorption：Transdermal bioavailability of testosterone[J]. J Pharm Sci， 1984，73(2)：283. [6] ZHENG J M. Novel Transdermal Drug Delivery System（经皮给药新剂型）[M]. Vol 1. Beijing： People′s Medical Publishing House， 2004：270-271. [7] LIU J P， ZHOU N. Studies on effects of enhancers on the aminophylline transdermal therapeutic system and its mechanism[J]. Chin Pharm J（中国药学杂志），2001，36(8)：534-536. [8] KEISUKE Y， YURI T， HIDERO A， et al. Effect of penetration enhancers on transdermal delivery of propofol[J]. Biol Pharm Bull，2009，32(4)：677-683. [9] NARISHETTY S T K， PANCHAGNULA R. Transdermal delivery of zidovudine： Effect of terpene and their mechanism of action[J]. J Controlled Release，2004，95(3)：367-379. [10] WILLIAMS A C， BARRY B W. Penetration enhancers[J]. Adv Drug Deliv Rev， 2004， 56(5)：603-618. [11] CHAI G B， PAN Y F， LI F Z. Effect of borneol/metholum eutectic mixture on nasal-brain delivery of neurotoxin loaded nanoparticles[J]. China J Chin Mater Med（中国中药杂志）， 2009，34(6)： 698-701. [12] HU H P， LUO F， ZHANG J Y， et al. Clinical observation of umbilical compressing with Chinese herbal medicine in treating children′s asthma[J]. J Pediat Tradit Chin Med（中医儿科杂志），2005，1(1)：29-34. [13] GU X L， YUAN X. Clinical application and nursing of Chinese medicine umbilical dressing therapy in pediatric[J]. Mod J Integr Tradit Chin West Med（现代中西医结合杂志），2009，18(2)：221-223. [14] TIAN H， GENG B J. Discussion on umbilical dressing therapy in emergency application[J]. Chin J Tradit Chin Med Pharm（中国中医药信息杂志），2010，17(12)：88-89.
