Phosphatidylcholine embedded microemulsions: physical properties and improved Caco-2 cell permeability.
The present study evaluates the effect of a solubilized model drug, diclofenac sodium salt (diclofenac), in our unique new U-type microemulsion system embedded with phosphatidylcholine (PC) in terms of microstructure transformations, physical properties of the system (viscosity, electrical conductivity), droplet sizes and shapes, and nucleation and growth of the droplets. The physical properties are correlated to the permeability of diclofenac through Caco-2 monolayer cells. The major findings reported are: (1) systems that are rich in surfactant and contain minimal oil phase form a microemulsion that enables high solubilization of diclofenac (20 wt.% diclofenac in the oil and surfactant concentrate can be fully diluted with water); (2) PC presence at the interface does not affect the size of the O/W droplets, while the presence of diclofenac at the interface decreases the O/W droplet size by an average of 50%; (3) diclofenac seems to increase incorporation of PC into the W/O interface; (4) diclofenac affects the physical properties of the microemulsion increasing the viscosity of the W/O microemulsion system and completely changing the conductivity profile of the system upon water dilution; (5) cryo-TEM images indicate that above 70 wt.% water the droplets are spherical; (6) diclofenac permeability through Caco-2 monolayer cells increases when PC is embedded into the interface.
Spernath
Aviram
A
Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
Aserin
Abraham
A
Ziserman
Lior
L
Danino
Dganit
D
Garti
Nissim
N
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004553:Electric Conductivity; D004655:Emulsions; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D008899:Mineral Oil / Q000737:chemistry; D015394:Molecular Structure; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry*; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D004655:Emulsions; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D004008:Diclofenac; D008899:Mineral Oil