title: Ropivacaine loaded microemulsion and microemulsion-based gel for transdermal delivery: preparation, optimization, and evaluation.
abstract: The objective of the present study was to prepare and evaluate a ropivacaine-loaded microemulsion (ME) formulation and microemulsion-based Carbopol gel (ME-gel) for transdermal delivery. Pseudo-ternary phase diagrams and a simplex lattice experiment design were utilized to screen and optimize the ME formulation. In the process, drug solubility and particle size were inspected as dependent variables whilst Capryol(®) 90 (X1), Smix (X2, Labrasol(®): absolute ethanol=1:2 w/w), water (X3) as independent variables. Following the optimization, the optimal ME formulation was comprised of 15% Capryol(®) 90, 53% Smix, and 32% water, respectively. Ropivacaine loaded ME appeared to be spherical under transmission electron microscope, and the average particle size was 58.79 nm. The results of ex vivo permeation study showed that ropivacaine had a significant higher cumulative amount from ME than that from ME-gel. Histopathology study elucidated that the microstructure of skin surface was significantly changed by the treatment of ME formulation. Skin irritation study indicated that neither ME nor ME-gel caused any irritation responses. Both ME and ME-gel presented a remarkable analgesic activity on acetic acid-induced writhing in mice. In conclusion, ME could be a promising formulation for ropivacaine transdermally administration.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: liujiyong@gmail.com.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000279:Administration, Cutaneous; D000577:Amides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D000077212:Ropivacaine; D012869:Skin Absorption; D012995:Solubility
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D004655:Emulsions; D005079:Excipients; D005782:Gels; D000077212:Ropivacaine
keywords: Analgesic activity; Carbopol; Microemulsion; Ropivacaine; Transdermal delivery