title: Cardiovascular effects of transdermally delivered bupranolol in rabbits: effect of chemical penetration enhancers.
abstract: Bupranolol is a promising candidate for transdermal drug delivery system (TDDS) development. The effect of permeation enhancers on the in vivo delivery and beta-blocking effect of reservoir type TDDS was studied in comparison with intravenous BPL in rabbits. The beta-blocking effect was quantified by measuring the inhibition of isoprenaline induced tachycardia in rabbits after BPL administration via transdermal and intravenous routes. The reservoir type TDDS containing a hydroxypropyl cellulose gel and polyethylene membrane was used as a control device. In comparison, the TDDS containing skin penetration enhancers, either 2-pyrrolidone or partially methylated beta cyclodextrin (PMbetaCD) were evaluated. The control device (no enhancer) produced about 52% inhibition of isoprenaline induced tachycardia at 2 h and the effect continued over 24 h application period, however, the devices with 2-pyrolidone or PMbetaCD produced about 85% inhibition of isoprenaline induced tachycardia at 3 h and the same effect continued over 24 h application period. Likewise, the AUC of these devices were significantly higher than that of control device. The intravenous bupranolol showed rapid decline in the pharmacodynamic effect with time indicating its rapid elimination. The in vivo delivery of bupranolol (as estimated by a mass balance study) from the devices made with pyrolidone or PMbetaCD was 3-fold higher than that of control. The results of this study strongly suggest that the penetration enhancers in the TDDS increased the in vivo delivery of BPL, thereby increased the beta-blocking activity of BPL by 50-60% higher than control, enabling the reduction of the TDDS patch size, accordingly.
authors: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, AL 36849, USA.
authors: R Jayachandra
authors: RJ
authors: Babu
authors: Muralikrishnan
authors: M
authors: Dhanasekaran
authors: Siva R
authors: SR
authors: Vaithiyalingam
authors: P N
authors: PN
authors: Singh
authors: J K
authors: JK
authors: Pandit
mesh_terms: D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002046:Bupranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004336:Drug Antagonism; D016503:Drug Delivery Systems; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010539:Permeability / Q000187:drug effects; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000319:Adrenergic beta-Antagonists; D011760:Pyrrolidinones; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002046:Bupranolol; C028537:2-pyrrolidone; D007545:Isoproterenol