Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration.
Clomethiazole (CMZ) was used as a model drug to be incorporated into an emulsion vehicle. The effects of drug concentration and number of homogenisation steps were evaluated using multiple linear regression. The droplet size, measured as a z-average diameter by photon correlation spectroscopy (PCS), was found to be between 60 and 260 nm in the investigated range of CMZ concentrations, highly dependent on the concentration, but more weakly so on the number of homogenisation steps. Slow-scanning high-sensitivity differential scanning calorimetry (DSC) measurements showed that CMZ depresses the phospholipid chain melting temperature in the emulsion system, whereas (13)C nuclear magnetic resonance (NMR) experiments suggested that the CMZ molecules are to a large extent located in the surface region of the emulsion droplets. This interpretation is compatible with results from NMR self-diffusion measurements, which showed that most of the CMZ molecules are rapidly exchanged between emulsion droplets and the aqueous surrounding. It can be concluded that the surface-active drug CMZ has a significant influence on the characteristics of phospholipid-stabilised emulsions through its ability to interact with the phospholipid interface. Thus, the results underline the importance of characterising drug-lipid interactions for the development of lipid-based formulations.
Nordén
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TP
AstraZeneca R&D Södertälje, SE-151 85, Södertälje, Sweden. tomas.petersson-norden@astrazeneca.com
Siekmann
B
B
Lundquist
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S
Malmsten
M
M
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000927:Anticonvulsants / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002719:Chlormethiazole / Q000737:chemistry*; D000074263:Coconut Oil; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D005217:Fat Emulsions, Intravenous; D007202:Indicators and Reagents / Q000737:chemistry; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010743:Phospholipids / Q000737:chemistry*; D010938:Plant Oils / Q000737:chemistry*; D014867:Water
D000927:Anticonvulsants; D005217:Fat Emulsions, Intravenous; D007202:Indicators and Reagents; D010743:Phospholipids; D010938:Plant Oils; D014867:Water; D002719:Chlormethiazole; D015060:1,2-Dipalmitoylphosphatidylcholine; D000074263:Coconut Oil; D004134:Dimyristoylphosphatidylcholine