Potential use of nanostructured lipid carriers for topical delivery of flurbiprofen.
The potential use of nanostructured lipid carriers (NLC) composed of a fatty acid [stearic acid (SA)] or a triglyceride (glyceryl behenate) as solid lipids, and a mixture of medium chain triglycerides and castor oil as liquid lipids, for skin administration of flurbiprofen (FB), has been explored. Two different optimized NLC formulations (FB-SANLC based on SA vs. FB-C888NLC based on glyceryl behenate), with respect to the morphometrical properties (particle size and polydispersity index) and the entrapment efficiency, were used in this study. The ex vivo permeation profiles of FB-C888NLC, FB-SANLC and conventional FB solution were evaluated using human skin. An improved FB permeation was observed when the drug was delivered by skin application of FB-C888NLC, attributed to the particle size and matrix crystallinity. The differential scanning calorimetry and X-ray diffraction studies suggested major polymorphic transitions in the lipid matrix of FB-C888NLC. A good correlation between polymorphic transitions and increased drug permeation was observed. However, both NLC dispersions showed a penetration-enhancing ratio (ER) higher than conventional FB solution. The in vitro and in vivo irritancy and local tolerability were assessed by running, respectively, the SKINTEX™ and Draize test. Both FB-C888NLC and FB-SANLC were classified as nonirritant.
González-Mira
E
E
Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain. eligonzalezmi@ub.edu
Nikolić
S
S
García
M L
ML
Egea
M A
MA
Souto
E B
EB
Calpena
A C
AC
D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002368:Castor Oil / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004339:Drug Compounding; D005227:Fatty Acids / Q000737:chemistry / Q000633:toxicity; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D008297:Male; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013229:Stearic Acids / Q000737:chemistry / Q000633:toxicity; D014280:Triglycerides / Q000737:chemistry / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005227:Fatty Acids; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D013229:Stearic Acids; D014280:Triglycerides; C086409:glyceryl behenate; C022834:miglyol 812; C031183:stearic acid; D005480:Flurbiprofen; D002368:Castor Oil