title: Dual-directional regulation of drug permeating amount by combining the technique of ion-pair complexation with chemical enhancers for the synchronous permeation of indapamide and bisoprolol in their compound patch through rabbit skin.
abstract: To achieve the synchronous skin permeation of indapamide (IND) and bisoprolol (BSP) in their compound patch, the techniques of ion-pair complexation and chemical enhancers were combined to dual-directionally regulate drug permeating amounts. Ion-pair complexes of BSP and various organic acids were formed by the technique of ion-pair complexation. Among the complexes formed, bisoprolol tartrate (BSP.T) down-regulated the permeating amount of BSP to the same extent as that of IND. Then, to simultaneously up-regulate the amounts of the two drugs, an enhancer combination of 15.8% Span80 (SP), 6.0% Azone (AZ) and 2.2% N-methyl pyrrolidone (NMP) was obtained by central composite design and exhibited an outstanding and simultaneous enhancement on IND and BSP with enhancing ratio (ER) of 4.52 and 3.49, respectively. The effect of the dual-directional regulation was evaluated by in vitro permeation experiments and in vivo pharmacokinetic studies. For IND and BSP, their observed permeation profiles were comparable and their MAT (mean absorption time) showed no significant difference, which both demonstrated these two drugs achieved the synchronous skin permeation in their compound patch by the dual-directional regulation strategy of combining the technique of ion-pair complexation with chemical enhancers.
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Wenting
authors: W
authors: Song
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Dongmei
authors: D
authors: Cun
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Peng
authors: P
authors: Quan
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Nannan
authors: N
authors: Liu
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Yang
authors: Y
authors: Chen
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Hongxia
authors: H
authors: Cui
authors: School of Medical Instrument, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: xrwlove@163.com.
authors: Rongwu
authors: R
authors: Xiang
authors: Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: fangliang2003@yahoo.com.
authors: Liang
authors: L
authors: Fang
mesh_terms: D000818:Animals; D001381:Azepines / Q000737:chemistry; D017298:Bisoprolol / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D015536:Down-Regulation; D004338:Drug Combinations; D004347:Drug Interactions; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D006601:Hexoses / Q000737:chemistry; D066298:In Vitro Techniques; D007190:Indapamide / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D010539:Permeability; D011760:Pyrrolidinones / Q000737:chemistry; D011817:Rabbits; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption; D013644:Tartrates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D057968:Transdermal Patch; D015854:Up-Regulation
chemical_list: D001381:Azepines; D004338:Drug Combinations; D005079:Excipients; D006601:Hexoses; D011760:Pyrrolidinones; D013644:Tartrates; C018665:sorbitan monooleate; C035229:laurocapram; D007190:Indapamide; C038678:N-methylpyrrolidone; D017298:Bisoprolol
keywords: Bisoprolol; Compound transdermal patch; Dual-directional regulation; Enhancer combination; Indapamide; Ion-pair; Synchronous permeation