title: Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2(3) factorial design and in vivo evaluation in rabbits.
abstract: BACKGROUND
  Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route.
  
  
  OBJECTIVE
  To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin.
  
  
  METHODS
  Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2(3) full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables.
  
  
  CONCLUSIONS
  The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm(2)/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 - α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety.
  
  
  CONCLUSIONS
  Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , October 6 University , 6 October Guiza , Egypt and.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Soliman
authors.affiliation: b Department of Pharmaceutics, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Nevine S
authors.initials: NS
authors.lastname: Abdelmalak
authors.affiliation: b Department of Pharmaceutics, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Omaima N
authors.initials: ON
authors.lastname: El-Gazayerly
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , October 6 University , 6 October Guiza , Egypt and.
authors.forename: Nabaweya
authors.initials: N
authors.lastname: Abdelaziz
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D004095:Dihydropyridines / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D004355:Drug Stability; D010539:Permeability; D011817:Rabbits; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004095:Dihydropyridines; D013501:Surface-Active Agents; C060285:lacidipine
keywords: 23 full factorial design; Bioavailability study; lacidipine; proniosomal gel; transdermal delivery